A Phase 1/2 interventional study of 5-Fluorouracil (5-FU) and Leucovorin in Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma or Esophageal Carcinoma, sponsored by Hoffmann-La Roche. Terminated at 28 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-03.
Sponsored by Hoffmann-La Roche · Phase 1/2, Interventional, and Treatment
A Phase Ib/II, open label, multi-center, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in patients with locally advanced unresectable or metastatic G/GEJ cancer (hereafter referred to as gastric cancer) and esophageal cancer. Two cohorts of patients with gastric cancer have been enrolled in parallel in this study: the second-line (2L) Gastric Cancer Cohort consists of patients with gastric cancer who have progressed after receiving a platinum-containing or fluoropyrimide-containing chemotherapy regimen in the first-line setting, and the first-line (1L) Gastric Cancer Cohort consists of patients with gastric cancer who have not received prior chemotherapy in this setting. In each cohort, eligible patients will be assigned to one of several treatment arms. Additionally, a cohort of patients with esophageal cancer who have not received prior systemic treatment for their disease will be enrolled in this study. Eligible patients will be randomized to chemotherapy or the combination of chemotherapy with checkpoint inhibitor immunotherapy.
1,873 studies on the registry are indexed under Esophageal Neoplasms; 501 are open to participants now.
This study's enrollment of 219 is above the median of 58 across 1,347 interventional studies indexed under Esophageal Neoplasms.
Browse Esophageal Neoplasms studies →Hoffmann-La Roche is the lead sponsor of 2,101 studies on the registry; 87 are open to participants now.
Of its 330 completed or terminated interventional studies of FDA-regulated products, 248 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Gastric Cancer Cohorts Inclusion Criteria:
Esophageal Cancer Cohort Inclusion Criteria:
For patients treated with chemotherapy in the locally advanced setting: occurrence of metastasis after 6 months from the last dose of chemotherapy;
Exclusion Criteria:
Exclusion criteria for the 2L Gastric Cancer Cohort:
Gastric Cancer Exclusion Criteria:
Esophageal Cancer Cohort Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in the 1L Gastric Cancer Control arm will receive modified FOLFOX6 (mFOLFOX6) treatment consisting of 5-fluorouracil (5-FU), leucovorin (folinic acid), and oxaliplatin. Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib treatment, provided they meet the eligibility criteria. No longer enrolling participants as of June 2018.
Drug: 5-Fluorouracil (5-FU) · Drug: Leucovorin · Drug: Oxaliplatin
Participants in the 1L-A Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab plus cobimetinib. No longer enrolling participants as of June 2018.
Drug: 5-Fluorouracil (5-FU) · Drug: Leucovorin · Drug: Oxaliplatin · Drug: Atezolizumab · Drug: Cobimetinib
Participants in the 1L-A2 Gastric Cancer arm will receive mFOLFOX6 treatment consisting of 5-FU, leucovorin and oxaliplatin in combination with atezolizumab during cycles 1 and 2 followed by atezolizumab plus cobimetinib during cycles 3 and beyond. No longer enrolling participants as of June 2018.
Drug: 5-Fluorouracil (5-FU) · Drug: Leucovorin · Drug: Oxaliplatin · Drug: Atezolizumab · Drug: Cobimetinib
Participants in the 2L Gastric Cancer Control arm received ramucirumab plus paclitaxel. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
Biological: Ramucirumab · Drug: Paclitaxel
Participants in the 2L-1 Gastric Cancer arm received atezolizumab in combination with cobimetinib. Enrollment completed as of October 2019.
Drug: Atezolizumab · Drug: Cobimetinib
Participants in the 2L-2 Gastric Cancer arm received atezolizumab in combination with PEGylated recombinant human hyaluronidase (PEGPH20). Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
Biological: PEGylated recombinant human hyaluronidase (PEGPH20) · Drug: Atezolizumab
Participants in the 2L-3 Gastric Cancer arm received atezolizumab in combination with BL-8040. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
Drug: BL-8040 · Drug: Atezolizumab
Participants in the 2L-4 Gastric Cancer arm received atezolizumab in combination with linagliptin. Participants who progressed on treatment had the option of receiving Atezolizumab + Cobimetinib treatment, provided they met the eligibility criteria. Enrollment completed as of October 2019.
Drug: Linagliptin · Drug: Atezolizumab
Participants in the 1L-1 Esophageal Cancer arm will receive atezolizumab in combination with tiragolumab and chemotherapy.
Drug: Atezolizumab · Drug: Cisplatin · Drug: Tiragolumab · Drug: 5-Fluorouracil (5-FU)
Participants in the 1L-2 Esophageal Cancer arm will receive atezolizumab in combination with chemotherapy.
Drug: Atezolizumab · Drug: Cisplatin · Drug: 5-Fluorouracil (5-FU)
Participants in the 1L-Control Eophageal Cancer arm will receive chemotherapy.
Drug: Cisplatin · Drug: 5-Fluorouracil (5-FU)
Participants in the 1L-3 Esophageal Cancer arm will receive atezolizumab + tiragolumab treatment. Participants from the cisplatin + 5-FU esophageal cancer cohort arm may be permitted to enroll in this arm if they progress after receiving chemotherapy.
Drug: Atezolizumab · Drug: Tiragolumab
5-FU 2400 milligrams per square meter (mg/m\^2) by continuous intravenous (IV) infusion over 46 hours on Days 1 and 2 and Days 15 and 16 of every 28-day cycle.
Leucovorin: 100 mg/m\^2 IV over 2 hours on Days 1 and 15 of every 28-day cycle.
Also known as: Folinic acid
Oxaliplatin: 100 mg/m\^2 administered by IV infusion over 2 hours on Days 1 and 15 of every 28-day cycle.
Atezolizumab: 840 mg by IV infusion on Days 1 and 15 of every 28-day cycle.
Also known as: Tecentriq
Cobimetinib: 60 mg by mouth once a day on Days 1-21 of every 28-day cycle
Also known as: Cotellic
Ramucirumab: 8 mg/kg administered by IV infusion over 60 minutes on Days 1 and 15 of every 28-day cycle.
Paclitaxel: 80 mg/m\^2 administered by IV infusion on Days 1, 8, and 15 of every 28-day cycle.
PEGPH20: 3 micrograms per kilogram (mcg/kg) administered by IV infusion on Days 1, 8, and 15 of every 21-day cycle.
BL-8040: 1.25 mg/kg administered by subcutaneous (SC) injection on Days 1-5 during the 5-day priming period prior to Cycle 1; 1.25 mg/kg administered by SC injection three times a week (Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of every 21-day cycle).
Linagliptin: 5 mg orally once a day of every 21-day cycle.
Atezolizumab: 1200 mg administered by IV infusion on Day 1 of every 21-day cycle
Also known as: Tecentriq
Cobimetinib: 40 or 60 mg (depending on the recommended dose determined during the safety run-in phase) by mouth once a day on Days 1-21 of every 28-day cycle.
Also known as: Cotellic
Cisplatin: 80 mg/m\^2 administered by IV infusion on Day 1 of each 21 day cycle. Treatment will be capped after 6 doses.
Tiragolumab: 600 mg administered by IV infusion on Day 1 of every 21 day cycle.
Also known as: RO7092284
5-FU 800 mg/m\^2 administerd by IV infusion on Days 1-5 of each 21 day cycle.
Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to RECIST v1.1
OR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart during Stage 1, as determined by the investigator using RECIST v.1.1. Objective response rate (ORR) was defined as the percentage of participants with OR. CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. 95% confidence intervals (CI) for rates were constructed using Clopper-Pearson method. Percentages have been rounded off.
Time frame: From randomization up to approximately 84.2 months
Stage 1: Progression Free Survival (PFS) After Randomization, as Determined by Investigator According to RECIST v1.1
PFS was defined as the time from randomization to the first occurrence of documented PD, as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or unequivocal progression of existing non-target lesions. Participants who did not have documented PD or death, PFS was censored at the day of the last tumor assessment. Kaplan-Meier (K-M) method was used to estimate PFS.
Time frame: From randomization to the first occurrence of PD or death (up to approximately 84.2 months)
Stage 1: Overall Survival (OS) After Randomization
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. K-M methodology was used to estimate the median OS.
Time frame: From randomization to death (up to approximately 84.2 months)
Stage 1: OS at Month 6 and Month 12
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. The K-M approach was used to estimate the percentage of participants who were event-free for OS at Month 6 and Month 12. Percentages have been rounded off.
Time frame: At Months 6 and 12
Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1
DOR was defined as time from first occurrence of a documented OR until the time of documented PD as determined by investigator assessment using RECIST v1.1 or death from any cause, whichever occurs first. CR was defined as the disappearance of all target \& non-target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD, in the absence of CR. PD=at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or unequivocal progression of existing non-target lesions. Participants who did not have documented PD or death, DOR was censored at the day of the last tumor assessment. K-M method was used to estimate DOR.
Time frame: Up to approximately 84.2 months
Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1
DC was defined as stable disease (SD) for ≥16 weeks for GC cohort or ≥ 12 weeks for esophageal cancer cohort, or CR/PR, as determined by investigator per RECIST v1.1. Disease control rate (DCR) was defined as percentage of participants with DC. CR was defined as disappearance of all target \& non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in SOD of target lesions, taking as reference baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as at least 20% increase in SOD of target lesions, taking as reference smallest sum on study including baseline (nadir). Additionally, the sum must also demonstrate absolute increase of at least 5 mm or unequivocal progression of existing non-target lesions. Percentages have been rounded off.
Time frame: Up to approximately 84.2 months
Stages 1 and 2: Percentage of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
Time frame: Stage 1: Up to 84.2 months; Stage 2: Up to 42.6 months
Stage 1: Serum Concentration of Atezolizumab
1 cycle = 21 days for the all three reported arms: Stage 1 Cohort 2: Atezolizumab + PEGPH20, Stage 1: Atezolizumab + Cisplatin + 5-FU" cohorts and Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU" cohort. The protocol pre-specified that PK assessments could be conducted only for treatment combinations selected by the sponsor for further development. As the sponsor decided not to continue further development of the mFOLFOX6 + atezolizumab + cobimetinib, atezolizumab + linagliptin, and atezolizumab + BL-8040 combinations, PK data were not reported for these cohorts.
Time frame: Pre-dose, 30 minutes (min) post-dose (infusion=60 min) on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20, 24, & 28; Stage 1 treatment discontinuation (TD) (up to approximately 82.7 months)
Stage 1: Serum Concentration of Tiragolumab
Time frame: Pre-dose, 30 min post-dose on Day 1 of Cycle 1; pre-dose on Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20, 24, & 28 (1 Cycle=28 days); Stage 1 TD (up to approximately 46.7 months)
Stage 1: Plasma Concentration of PEGPH20
1 Cycle=21 days
Time frame: Pre-dose: Day 1 of Cycles 1, 2, 3, 4 & Days 8, 15 of Cycle 1; 5 minutes & 1-3 hours post-dose: Day 1 Cycle 1; 5 min post-dose: Day 1 Cycle 2; Stage 1: TD (up to approx 3.3 months) & Day 120 post last dose of atezo (up to approx 6.8 months)
Stage 1: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) to Atezolizumab
Participants who received atezolizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following atezolizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample have been reported here. The protocol pre-specified that ADA assessments could be conducted only for treatment combinations selected by the sponsor for further development. As the sponsor decided not to continue further development of the mFOLFOX6 + atezolizumab + cobimetinib, atezolizumab + linagliptin, and atezolizumab + BL-8040 combinations, ADA data were not reported for these cohorts.
Time frame: Up to approximately 82.7 months
Stage 1: Number of Participants With Treatment-emergent ADAs to Tiragolumab
Participants who received tiragolumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following tiragolumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 t.u. greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.
Time frame: Up to approximately 46.7 months
Stage 1: Number of Participants With Treatment-emergent ADAs to PEGPH20
Participants who received PEGPH20 were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following PEGPH20 exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 t.u. greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.
Time frame: Up to approximately 3.3 months
A total of 219 participants with metastatic gastric or esophageal cancer took part in the study from 13 Oct 2017 to 09 Oct 2025. The study enrolled participants with gastric cancer (GC) in 2 cohorts: Cohort 1: received no prior systemic therapy for GC \& Cohort 2: received 1 prior line of systemic therapy for GC and participants with esophageal cancer in 1 cohort (received no prior systemic treatment).
| Milestone | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU | Stage 2: Atezolizumab + Tiragolumab |
|---|---|---|---|---|---|---|---|---|---|
| Started | 5 | 16 | 15 | 15 | 16 | 24 | 65 | 63 | 0 |
| Safety-evaluable (se) population | 5 | 12 | 13 | 13 | 14 | 23 | 65 | 62 | 0 |
| Efficacy population | 5 | 12 | 13 | 13 | 14 | 23 | 65 | 62 | 0 |
| Completed | 4 | 11 | 13 | 12 | 11 | 23 | 61 | 57 | 0 |
| Not completed | 1 | 5 | 2 | 3 | 5 | 1 | 4 | 6 | 0 |
| Withdrew: Progression of disease | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Protocol violation | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Death | 0 | 1 | 0 | 0 | 2 | 0 | 1 | 3 | 0 |
| Withdrew: Withdrawal by subject | 0 | 3 | 1 | 1 | 0 | 1 | 1 | 0 | 0 |
| Withdrew: Reason not specified | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Physician decision | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 |
| Withdrew: Study terminated by sponsor | 0 | 0 | 0 | 1 | 1 | 0 | 2 | 1 | 0 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Milestone | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU | Stage 2: Atezolizumab + Tiragolumab |
|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 15 |
| Se population | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 14 |
| Efficacy population | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 14 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 15 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU | Stage 2: Atezolizumab + Tiragolumab |
|---|---|---|---|---|---|---|---|---|---|
| Started | 4 | 11 | 13 | 12 | 11 | 8 | 61 | 57 | 15 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 4 | 11 | 13 | 12 | 11 | 8 | 61 | 57 | 15 |
| Withdrew: Study terminated by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 11 | 4 |
| Withdrew: Death | 3 | 11 | 13 | 10 | 10 | 7 | 55 | 42 | 11 |
| Withdrew: Lost to follow-up | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 |
| Withdrew: Symptomatic deterioration | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 3 | 0 |
OR was defined as a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart during Stage 1, as determined by the investigator using RECIST v.1.1. Objective response rate (ORR) was defined as the percentage of participants with OR. CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. 95% confidence intervals (CI) for rates were constructed using Clopper-Pearson method. Percentages have been rounded off.
| percentage of participants | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU |
|---|---|---|---|---|---|---|---|---|
| Stage 1: Percentage of Participants With Objective Response (OR), as Determined by Investigator According to RECIST v1.1 | 40.0 (5.27 to 85.34) | 16.7 (2.09 to 48.41) | 0 (0.00 to 24.71) | 15.4 (1.92 to 45.45) | 21.4 (4.66 to 50.80) | 47.8 (26.82 to 69.41) | 53.8 (41.03 to 66.30) | 67.7 (54.66 to 79.06) |
PFS was defined as the time from randomization to the first occurrence of documented PD, as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or unequivocal progression of existing non-target lesions. Participants who did not have documented PD or death, PFS was censored at the day of the last tumor assessment. Kaplan-Meier (K-M) method was used to estimate PFS.
| months | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU |
|---|---|---|---|---|---|---|---|---|
| Stage 1: Progression Free Survival (PFS) After Randomization, as Determined by Investigator According to RECIST v1.1 | 14.93 (10.64 to NA) | 6.06 (3.68 to 8.77) | 1.84 (1.48 to 2.10) | 1.97 (1.71 to 7.92) | 1.95 (1.64 to 4.93) | 5.98 (2.69 to 8.11) | 7.03 (5.55 to 8.28) | 6.90 (5.95 to 9.89) |
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. K-M methodology was used to estimate the median OS.
| months | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU |
|---|---|---|---|---|---|---|---|---|
| Stage 1: Overall Survival (OS) After Randomization | 16.99 (14.65 to NA) | 8.33 (6.37 to 10.94) | 7.00 (5.26 to 8.87) | 10.64 (3.71 to 39.06) | 8.57 (4.27 to 28.12) | 10.09 (7.59 to 23.20) | 12.98 (11.17 to 15.70) | 16.56 (12.22 to 21.03) |
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. The K-M approach was used to estimate the percentage of participants who were event-free for OS at Month 6 and Month 12. Percentages have been rounded off.
| percentage of participants | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU |
|---|---|---|---|---|---|---|---|---|
| Month 6 | 100.00 (100.00 to 100.00) | 75.00 (50.50 to 99.50) | 53.85 (26.75 to 80.95) | 51.28 (23.10 to 79.47) | 56.25 (29.80 to 82.70) | 78.02 (60.98 to 95.06) | 87.52 (79.43 to 95.61) | 88.65 (80.73 to 96.57) |
| Month 12 | 100.00 (100.00 to 100.00) | 25.00 (0.50 to 49.50) | 23.08 (0.17 to 45.98) | 42.74 (14.71 to 70.76) | 40.18 (13.51 to 66.85) | 36.71 (16.54 to 56.89) | 57.83 (45.73 to 69.92) | 65.36 (53.36 to 77.36) |
DOR was defined as time from first occurrence of a documented OR until the time of documented PD as determined by investigator assessment using RECIST v1.1 or death from any cause, whichever occurs first. CR was defined as the disappearance of all target \& non-target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD, in the absence of CR. PD=at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or unequivocal progression of existing non-target lesions. Participants who did not have documented PD or death, DOR was censored at the day of the last tumor assessment. K-M method was used to estimate DOR.
| months | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU |
|---|---|---|---|---|---|---|---|---|
| Stage 1: Duration of Response (DOR), as Determined by Investigator According to RECIST v1.1 | NA (NA to NA) | 3.32 (2.89 to 3.75) | — | NA (58.84 to NA) | 14.46 (3.55 to NA) | 5.91 (2.83 to 14.06) | 6.90 (5.32 to 8.77) | 7.16 (4.40 to 15.31) |
DC was defined as stable disease (SD) for ≥16 weeks for GC cohort or ≥ 12 weeks for esophageal cancer cohort, or CR/PR, as determined by investigator per RECIST v1.1. Disease control rate (DCR) was defined as percentage of participants with DC. CR was defined as disappearance of all target \& non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least 30% decrease in SOD of target lesions, taking as reference baseline SOD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as at least 20% increase in SOD of target lesions, taking as reference smallest sum on study including baseline (nadir). Additionally, the sum must also demonstrate absolute increase of at least 5 mm or unequivocal progression of existing non-target lesions. Percentages have been rounded off.
| percentage of participants | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU |
|---|---|---|---|---|---|---|---|---|
| Stage 1: Percentage of Participants With Disease Control (DC), as Determined by Investigator According to RECIST v1.1 | 80.0 (28.36 to 99.49) | 66.7 (34.89 to 90.08) | 0 (0.00 to 24.71) | 23.1 (5.04 to 53.81) | 21.4 (4.66 to 50.80) | 56.5 (34.49 to 76.81) | 78.5 (66.51 to 87.69) | 83.9 (72.33 to 91.98) |
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
| percentage of participants | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU | Stage 2: Atezolizumab + Tiragolumab |
|---|---|---|---|---|---|---|---|---|---|
| Stages 1 and 2: Percentage of Participants With Adverse Events (AEs) | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
1 cycle = 21 days for the all three reported arms: Stage 1 Cohort 2: Atezolizumab + PEGPH20, Stage 1: Atezolizumab + Cisplatin + 5-FU" cohorts and Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU" cohort. The protocol pre-specified that PK assessments could be conducted only for treatment combinations selected by the sponsor for further development. As the sponsor decided not to continue further development of the mFOLFOX6 + atezolizumab + cobimetinib, atezolizumab + linagliptin, and atezolizumab + BL-8040 combinations, PK data were not reported for these cohorts.
| micrograms per milliliter (μg/mL) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU |
|---|---|---|---|
| Pre-dose on Day 1 of Cycle 1 | NA ± NA | NA ± NA | NA ± NA |
| 30 min post-dose on Day 1 of Cycle 1 | 362 ± 39.2 | 375 ± 21.6 | 379 ± 22.2 |
| Pre-dose on Day 1 of Cycle 2 | 64.4 ± 28.0 | 70.9 ± 48.8 | 60.8 ± 43.9 |
| Pre-dose on Day 1 of Cycle 3 | 95.6 ± 37.2 | 113 ± 54.3 | 87.3 ± 77.3 |
| Pre-dose on Day 1 of Cycle 4 | 117 ± NA | 137 ± 47.6 | 108 ± 56.8 |
| Pre-dose on Day 1 of Cycle 8 | — | 216 ± 37.1 | 185 ± 44.6 |
| Pre-dose on Day 1 of Cycle 12 | — | 204 ± 29.1 | 159 ± 46.7 |
| Pre-dose on Day 1 of Cycle 16 | — | 289 ± 29.2 | 206 ± 34.2 |
| Pre-dose on Day 1 of Cycle 20 | — | — | 273 ± 15.5 |
| Pre-dose on Day 1 of Cycle 24 | — | — | 239 ± 35.1 |
| Pre-dose on Day 1 of Cycle 28 | — | — | 209 ± NA |
| Stage 1 TD | 93.7 ± 58.5 | 195 ± 55.9 | 89.8 ± 130.7 |
| μg/mL | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU |
|---|---|
| Pre-dose on Day 1 of Cycle 1 | NA ± NA |
| 30 min post-dose on Day 1 of Cycle 1 | 223 ± 20.8 |
| Pre-dose on Day 1 of Cycle 2 | 31.4 ± 45.6 |
| Pre-dose on Day 1 of Cycle 3 | 43.3 ± 85.1 |
| Pre-dose on Day 1 of Cycle 4 | 50.5 ± 62.1 |
| Pre-dose on Day 1 of Cycle 8 | 83.4 ± 39.1 |
| Pre-dose on Day 1 of Cycle 12 | 76.1 ± 58.2 |
| Pre-dose on Day 1 of Cycle 16 | 87.6 ± 30.9 |
| Pre-dose on Day 1 of Cycle 20 | 102 ± 15.9 |
| Pre-dose on Day 1 of Cycle 24 | 97.8 ± 38.3 |
| Pre-dose on Day 1 of Cycle 28 | 90.0 ± NA |
| Stage 1 TD | 39.8 ± 166.4 |
1 Cycle=21 days
| μg/mL | Stage 1 Cohort 2: Atezolizumab + PEGPH20 |
|---|---|
| Pre-dose on Day 1 of Cycle 1 | NA ± NA |
| 5 min post-dose on Day 1 of Cycle 1 | 31.4 ± 1290.5 |
| 1-3 h post-dose on Day 1 of Cycle 1 | 25.8 ± 1086.5 |
| Pre-dose on Day 8 of Cycle 1 | 0.529 ± NA |
| Pre-dose on Day 15 of Cycle 1 | 0.485 ± NA |
| Pre-dose on Day 1 of Cycle 2 | 0.647 ± NA |
| 5 min post-dose on Day 1 of Cycle 2 | 56.3 ± 42.8 |
| Pre-dose on Day 1 of Cycle 3 | 1.92 ± 1992.5 |
| Pre-dose on Day 1 of Cycle 4 | 10.2 ± NA |
| Stage 1 TD | 2.12 ± 1276.5 |
| Stage 1 Day 120 post last dose | 0.0375 ± NA |
Participants who received atezolizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following atezolizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample have been reported here. The protocol pre-specified that ADA assessments could be conducted only for treatment combinations selected by the sponsor for further development. As the sponsor decided not to continue further development of the mFOLFOX6 + atezolizumab + cobimetinib, atezolizumab + linagliptin, and atezolizumab + BL-8040 combinations, ADA data were not reported for these cohorts.
| Participants | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU |
|---|---|---|---|
| Stage 1: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) to Atezolizumab | 3 | 5 | 8 |
Participants who received tiragolumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following tiragolumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 t.u. greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.
| Participants | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU |
|---|---|
| Stage 1: Number of Participants With Treatment-emergent ADAs to Tiragolumab | 0 |
Participants who received PEGPH20 were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following PEGPH20 exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 t.u. greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.
| Participants | Stage 1 Cohort 2: Atezolizumab + PEGPH20 |
|---|---|
| Stage 1: Number of Participants With Treatment-emergent ADAs to PEGPH20 | 0 |
Collected over Stage 1: Up to 84.2 months; Stage 2: Up to 42.6 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | 4/5 (80%) | 2/5 (40%) | 5/5 (100%) |
| Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | 12/16 (75%) | 6/12 (50%) | 12/12 (100%) |
| Stage 1 Cohort 2: Atezolizumab + PEGPH20 | 13/15 (86.7%) | 1/13 (7.7%) | 13/13 (100%) |
| Stage 1 Cohort 2: Atezolizumab + BL-8040 | 11/15 (73.3%) | 5/13 (38.5%) | 13/13 (100%) |
| Stage 1 Cohort 2: Atezolizumab + Linagliptin | 13/16 (81.3%) | 4/14 (28.6%) | 14/14 (100%) |
| Stage 1: Cisplatin + 5-FU (Control) | 8/24 (33.3%) | 11/23 (47.8%) | 23/23 (100%) |
| Stage 1: Atezolizumab + Cisplatin + 5-FU | 56/65 (86.2%) | 34/65 (52.3%) | 65/65 (100%) |
| Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU | 45/63 (71.4%) | 38/62 (61.3%) | 62/62 (100%) |
| Stage 2: Atezolizumab + Tiragolumab | 11/15 (73.3%) | 7/14 (50%) | 14/14 (100%) |
| Event | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU | Stage 2: Atezolizumab + Tiragolumab |
|---|---|---|---|---|---|---|---|---|---|
| Gastrointestinal haemorrhageGastrointestinal disorders | 1/5 | 0/12 | 0/13 | 0/13 | 0/14 | 1/23 | 1/65 | 1/62 | 1/14 |
| Small intestinal obstructionGastrointestinal disorders | 1/5 | 0/12 | 0/13 | 0/13 | 0/14 | 0/23 | 0/65 | 0/62 | 0/14 |
| Cerebrovascular accidentNervous system disorders | 1/5 | 0/12 | 0/13 | 0/13 | 0/14 | 0/23 | 0/65 | 0/62 | 0/14 |
| PyrexiaGeneral disorders | 0/5 | 0/12 | 0/13 | 2/13 | 0/14 | 0/23 | 2/65 | 4/62 | 0/14 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/5 | 0/12 | 0/13 | 2/13 | 0/14 | 0/23 | 1/65 | 1/62 | 0/14 |
| PneumoniaInfections and infestations | 0/5 | 0/12 | 0/13 | 0/13 | 0/14 | 0/23 | 5/65 | 3/62 | 2/14 |
| DysphagiaGastrointestinal disorders | 0/5 | 0/12 | 1/13 | 0/13 | 0/14 | 2/23 | 5/65 | 5/62 | 0/14 |
| IleusGastrointestinal disorders | 0/5 | 1/12 | 0/13 | 0/13 | 0/14 | 1/23 | 0/65 | 0/62 | 1/14 |
| NauseaGastrointestinal disorders | 0/5 | 1/12 | 0/13 | 1/13 | 0/14 | 0/23 | 2/65 | 2/62 | 0/14 |
| Obstruction gastricGastrointestinal disorders | 0/5 | 1/12 | 0/13 | 0/13 | 0/14 | 0/23 | 1/65 | 0/62 | 0/14 |
| Event | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU | Stage 2: Atezolizumab + Tiragolumab |
|---|---|---|---|---|---|---|---|---|---|
| Decreased appetiteMetabolism and nutrition disorders | 5/5 | 6/12 | 6/13 | 5/13 | 6/14 | 15/23 | 34/65 | 33/62 | 1/14 |
| FatigueGeneral disorders | 4/5 | 4/12 | 3/13 | 3/13 | 3/14 | 8/23 | 31/65 | 19/62 | 2/14 |
| NauseaGastrointestinal disorders | 1/5 | 3/12 | 3/13 | 4/13 | 2/14 | 18/23 | 51/65 | 49/62 | 2/14 |
| Injection related reactionInjury, poisoning and procedural complications | 0/5 | 0/12 | 0/13 | 9/13 | 0/14 | 0/23 | 0/65 | 0/62 | 0/14 |
| AnaemiaBlood and lymphatic system disorders | 3/5 | 4/12 | 1/13 | 4/13 | 3/14 | 6/23 | 27/65 | 20/62 | 4/14 |
| DiarrhoeaGastrointestinal disorders | 3/5 | 3/12 | 1/13 | 2/13 | 1/14 | 5/23 | 18/65 | 31/62 | 1/14 |
| VomitingGastrointestinal disorders | 3/5 | 2/12 | 3/13 | 1/13 | 1/14 | 3/23 | 16/65 | 20/62 | 0/14 |
| Back painMusculoskeletal and connective tissue disorders | 3/5 | 1/12 | 2/13 | 0/13 | 2/14 | 2/23 | 11/65 | 9/62 | 3/14 |
| Peripheral sensory neuropathyNervous system disorders | 3/5 | 2/12 | 2/13 | 0/13 | 1/14 | 8/23 | 7/65 | 4/62 | 0/14 |
| Dermatitis acneiformSkin and subcutaneous tissue disorders | 3/5 | 0/12 | 0/13 | 0/13 | 0/14 | 0/23 | 1/65 | 0/62 | 0/14 |
All randomized population included all randomized participants.
| Age, Customized(Participants) | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU | Stage 2: Atezolizumab + Tiragolumab | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Stage 1: Adults (18-64 years) | 2 | 9 | 11 | 11 | 14 | 21 | 38 | 31 | — | 137 |
| Stage 1: From 65-84 years | 3 | 7 | 4 | 4 | 2 | 2 | 27 | 32 | — | 81 |
| Stage 1: 85 years and over | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | — | 1 |
| Stage 2: Adults (18-64 years) | — | — | — | — | — | — | — | — | 11 | 11 |
| Stage 2: From 65-84 years | — | — | — | — | — | — | — | — | 3 | 3 |
| Stage 2: 85 years and over | — | — | — | — | — | — | — | — | 0 | 0 |
| Sex: Female, Male(Participants) | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU | Stage 2: Atezolizumab + Tiragolumab | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Stage 1 — Female | 1 | 4 | 3 | 2 | 2 | 0 | 6 | 10 | — | 28 |
| Stage 1 — Male | 4 | 12 | 12 | 13 | 14 | 24 | 59 | 53 | — | 191 |
| Stage 2 — Female | — | — | — | — | — | — | — | — | 0 | 0 |
| Stage 2 — Male | — | — | — | — | — | — | — | — | 15 | 15 |
| Ethnicity (NIH/OMB)(Participants) | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU | Stage 2: Atezolizumab + Tiragolumab | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Stage 1 — Hispanic or Latino | 0 | 0 | 0 | 2 | 0 | 1 | 2 | 0 | — | 5 |
| Stage 1 — Not Hispanic or Latino | 5 | 16 | 15 | 11 | 16 | 22 | 61 | 62 | — | 208 |
| Stage 1 — Unknown or Not Reported | 0 | 0 | 0 | 2 | 0 | 1 | 2 | 1 | — | 6 |
| Stage 2 — Hispanic or Latino | — | — | — | — | — | — | — | — | 0 | 0 |
| Stage 2 — Not Hispanic or Latino | — | — | — | — | — | — | — | — | 14 | 14 |
| Stage 2 — Unknown or Not Reported | — | — | — | — | — | — | — | — | 1 | 1 |
| Race (NIH/OMB)(Participants) | Stage 1 Cohort 1: mFOLFOX6 + Atezolizumab + Cobimetinib | Stage 1 Cohort 2: Ramucirumab + Paclitaxel (Control) | Stage 1 Cohort 2: Atezolizumab + PEGPH20 | Stage 1 Cohort 2: Atezolizumab + BL-8040 | Stage 1 Cohort 2: Atezolizumab + Linagliptin | Stage 1: Cisplatin + 5-FU (Control) | Stage 1: Atezolizumab + Cisplatin + 5-FU | Stage 1: Atezolizumab +Tiragolumab + Cisplatin +5-FU | Stage 2: Atezolizumab + Tiragolumab | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Stage 1 — American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | 0 |
| Stage 1 — Asian | 3 | 10 | 8 | 7 | 11 | 18 | 37 | 43 | — | 137 |
| Stage 1 — Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | — | 1 |
| Stage 1 — Black or African American | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | — | 1 |
| Stage 1 — White | 2 | 6 | 7 | 6 | 4 | 6 | 26 | 18 | — | 75 |
| Stage 1 — More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | 0 |
| Stage 1 — Unknown or Not Reported | 0 | 0 | 0 | 2 | 1 | 0 | 1 | 1 | — | 5 |
| Stage 2 — American Indian or Alaska Native | — | — | — | — | — | — | — | — | 0 | 0 |
| Stage 2 — Asian | — | — | — | — | — | — | — | — | 12 | 12 |
| Stage 2 — Native Hawaiian or Other Pacific Islander | — | — | — | — | — | — | — | — | 0 | 0 |
| Stage 2 — Black or African American | — | — | — | — | — | — | — | — | 0 | 0 |
| Stage 2 — White | — | — | — | — | — | — | — | — | 3 | 3 |
| Stage 2 — More than one race | — | — | — | — | — | — | — | — | 0 | 0 |
| Stage 2 — Unknown or Not Reported | — | — | — | — | — | — | — | — | 0 | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
Ran from Oct 2017 to primary completion in Oct 2025, 95 months.
Results were first posted in Aug 2026, 9 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Fluorouracil · Leucovorin · Oxaliplatin · Cobimetinib · Hyaluronidase (human recombinant) · Motixafortide · Linagliptin · Cisplatin · Tiragolumab