A Phase 2 interventional study of Zenocutuzumab and Trastuzumab in Breast Cancer Metastatic, sponsored by Merus N.V.. Completed at 25 sites in 7 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-07.
Sponsored by Merus N.V. (part of Genmab) · Phase 2, Interventional, and Treatment
A Phase 2, open-label, multicenter international study will be performed to evaluate the efficacy of MCLA-128-based combinations. Three combination treatments will be evaluated, two in Cohort 1 and one in Cohort 2.
MCLA-128 (zenocutuzumab) is given in combinations in two metastatic breast cancer (MBC) populations, Human Epidermal Growth Factor Receptor (HER) 2-positive/amplified (Cohort 1) and Estrogen Receptor-positive/low HER2 expression (Cohort2).
Two combinations treatments will be evaluated in Cohort 1, the doublet and triplet. Initially zenocutuzumab is given in combination with trastuzumab in the doublet. After the safety of the doublet has been assessed in 4-6 patients, MCLA-128 is given in combination with trastuzumab and vinorelbine in the triplet, in parallel to the efficacy expansion of the doublet.
The doublet and triplet combinations are both evaluated in two steps with an initial safety run-in followed by a cohort efficacy expansion. In total up to 40 patients evaluable for efficacy are included in both the doublet and triplet.
In Cohort 2 zenocutuzumab is administered in combination with the same previous endocrine therapy on which progressive disease is radiologically documented. A total of up to 40 patients evaluable for efficacy are included in the Cohort 2.
Study Design Phase 2, open-label, multicenter international study to evaluate the efficacy of MCLA-128 (zenocutuzumab)-based combinations in 2 metastatic breast cancer populations, Human Epidermal Growth Factor Receptor (HER)2-positive/amplified (Cohort 1) and estrogen receptor-positive/low-HER2 expression (Cohort 2). Three combination treatments were evaluated, 2 in Cohort 1 and 1 in Cohort 2.
Cohort 1: To be eligible, patients had to have HER2-positive/amplified metastatic breast cancer, with confirmed HER2 overexpression by Immunohistochemistry (IHC) with a score of 3+ or of 2+ combined with positive Fluorescence in Situ Hybridization (FISH), have received up to 5 lines of HER2-directed therapy in the metastatic setting, and have progressed on the most recent line per Response Evaluation Criteria In Solid Tumors Guidelines (RECIST) v1.1, and have been previously treated with trastuzumab, pertuzumab and an HER2 Antibody-Drug Conjugates (ADC) in any sequence and any setting.
Initially zenocutuzumab was administered with trastuzumab (doublet combination). Safety was reviewed by an Independent Data Monitoring Committee (IDMC). If the safety of the doublet was approved, the triplet combination of zenocutuzumab plus trastuzumab and vinorelbine was to be evaluated in parallel with the doublet combination.
The doublet and triplet Cohort 1 combinations were each evaluated in 2 steps with an initial safety run-in period in 4 to 6 patients who were reviewed by the IDMC before deciding to expand the cohort. The triplet combination go/no-go decision was made by the IDMC after evaluation of the doublet safety run-in patients (based on Adverse Avents [AEs], Serious Adverse Events [SAEs], relationship to study drug, and other clinically relevant parameters [eg, laboratory parameters], available pharmacokinetics, immunogenicity, and cytokine data). If the triplet combination was considered safe, the expansion of the doublet and triplet combinations was performed in parallel. Patients were included in the triplet or doublet in a 3:1 ratio, taking into account previous exposure to vinorelbine.
After the safety run-in, if Cohort 1 doublet and Cohort 1 triplet combination therapies were considered tolerable by the IDMC, they were each to be expanded to a total of up to 40 patients evaluable for efficacy. If the doublet combination regimen was not well tolerated, Cohort 1 was to be closed. If the triplet combination was not well tolerated but the doublet was acceptable, the doublet expansion was to be continued.
Cohort 2: To be eligible, patients had to have estrogen receptor-positive and low-HER2 expression metastatic breast cancer (IHC 1+, or IHC 2+ combined with negative FISH), and radiologic or photographic evidence of disease progression on the last line of prior endocrine therapy (administered for ≥12 weeks) that included an aromatase inhibitor (AI) or fulvestrant. Patients who had received up to 3 prior endocrine therapies in the metastatic setting and had progressed on a Cyclin-Dependent Kinase (CDK) inhibitor (in any line) were eligible.
Zenocutuzumab was administered in combination with the same previous endocrine therapy on which progressive disease was radiologically/photographically documented. Up to 40 patients evaluable for efficacy were included.
Merus N.V. is the lead sponsor of 3 studies on the registry; none are open to participants now.
First submitted before Merus N.V. became part of Genmab.
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.
Women with or cytologically confirmed breast cancer with evidence of or locally advanced disease not amenable to any local therapy with curative intent:
2.1 Cohort 1 (zenocutuzumab + trastuzumab ± vinorelbine)
2.2 Cohort 2 (zenocutuzumab + endocrine therapy)
Adequate organ function:
Exclusion Criteria
Exposure to the following cumulative anthracycline doses:
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.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
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 biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
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.
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 share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
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.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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 drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
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.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
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.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
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.
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.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
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.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
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.
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.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (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.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
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.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
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.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
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.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
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.
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.
zenocutuzumab + trastuzumab
Drug: Zenocutuzumab · Drug: Trastuzumab
zenocutuzumab + trastuzumab + vinorelbine
Drug: Zenocutuzumab · Drug: Trastuzumab · Drug: Vinorelbine
zenocutuzumab + endocrine therapy
Drug: Zenocutuzumab · Drug: Endocrine therapy
full length immunoglobulin gamma-1 (IgG1) bispecific antibody targeting Human Epidermal Growth Factor Receptor (HER)2 and HER3
Also known as: MCLA-128
humanised IgG1 monoclonal antibody
Also known as: Herceptin
antineoplastic drug of vinca alkaloid family
Also known as: Navelbine, vinorelbine tartrate
same endocrine therapy is administered as the last line of endocrine therapy
Also known as: fulvestrant, exemestane, letrozole, anastrazole
This study also gives Fulvestrant, Anastrozole, Exemestane. No intervention listed here names it: that was found by reading the record.
Clinical Benefit Rate at 24 Weeks
Clinical benefit rate (CBR) at 24 weeks per investigator assessment. CBR is the proportion of patients with confirmed Complete Response (CR) or Partial Response (PR), or Stable Disease (SD) lasting 24 weeks.
Time frame: 24 weeks
Progression Free Survival (PFS) Per Investigator Assessment
For assessment per Response Evaluation Criteria In Solid Tumors Guidelines (RECIST) v1.1, PFS is the time from the date of treatment start to the date of event defined as the first documented progression or death due to any cause.
Time frame: Baseline, every 6 weeks until end of treatment, every 3 months thereafter up to 1 year after treatment (if not progressed at end of treatment)
Progression Free Survival (PFS) Per Central Review
For assessment per RECIST v1.1, PFS is the time from the date of treatment start to the date of event defined as the first documented progression or death due to any cause.
Time frame: Baseline, every 6 weeks until end of treatment, every 3 months thereafter up to 1 year after treatment (if not progressed at end of treatment)
Overall Response Rate (ORR) Per Investigator Assessment
The proportion of patients with overall response of Complete Response or Partial Response based upon RECIST 1.1 (confirmed response).
Time frame: Baseline, every 6 weeks until end of treatment, every 3 months thereafter up to 1 year after treatment (if not progressed at end of treatment)
Overall Response Rate (ORR) Per Central Review
The proportion of patients with overall response of Complete Response or Partial Response based upon RECIST 1.1 (confirmed response).
Time frame: Baseline, every 6 weeks until end of treatment, every 3 months thereafter up to 1 year after treatment (if not progressed at end of treatment)
Duration of Response (DoR) Per Investigator Assessment
DoR applies only to patients with a Best Overall Response (BOR) of confirmed CR or PR (RECIST v1.1). For RECIST v1.1, DoR is defined as the time from the date of the first documented response (CR or PR) to the date of first documented progression, or death due to any cause.
Time frame: Baseline, every 6 weeks until end of treatment, every 3 months thereafter up to 1 year after treatment (if not progressed at end of treatment)
Duration of Response (DoR) Per Central Review
DoR applies only to patients with a BOR of confirmed CR or PR (RECIST v1.1). For RECIST v1.1, DOR is defined as the time from the date of the first documented response (CR or PR) to the date of first documented progression, or death due to any cause.
Time frame: Baseline, every 6 weeks until end of treatment, every 3 months thereafter up to 1 year after treatment (if not progressed at end of treatment)
Overall Survival (OS)
The time from treatment start until death due to any cause.
Time frame: Baseline, every 6 weeks until end of treatment, every 3 months thereafter up to 1 year after treatment (if not progressed at end of treatment)
Number of Patients With Adverse Events (AE's) Leading to Discontinuation of Study Drug
Evaluation of number of participants with Adverse Events leading to leading to discontinuation of study drug
Time frame: During study treatment and up to 30 days after last administration of study drug (median duration of zenocutuzumab exposure was 6.0 weeks for Cohort 1 doublet, 19.3 weeks for Cohort 1 triplet and 11.8 weeks for Cohort 2).
Number of Patients With AE's of Special Interest (AESI)
AESIs for MCLA-128 combinations include: Infusion-related reactions (for any antibodies, known AESI for MCLA-128) Cardiotoxicity (anti-Human Epidermal Growth Factor Receptor (HER)2 therapy) Diarrhea (anti-HER2 therapy) Myelosuppression (vinorelbine)
Time frame: During study treatment and up to 30 days after last administration of study drug (median duration of zenocutuzumab exposure was 6.0 weeks for Cohort 1 doublet, 19.3 weeks for Cohort 1 triplet and 11.8 weeks for Cohort 2).
Anti-drug Antibodies Serum Titers
Number of patients with anti-drug antibodies at baseline and on treatment
Time frame: Pre-dose for each of cycles 1, 3 and 5, and every 4 cycles thereafter, and at the End of Treatment visit.
| Milestone | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Started | 15 | 39 | 50 |
| Completed | 0 | 0 | 0 |
| Not completed | 15 | 39 | 50 |
| Withdrew: Progressive disease (pd) | 15 | 30 | 47 |
| Withdrew: Subject withdrawal of all treatment and follow-up with agreement for contact | 0 | 2 | 0 |
| Withdrew: Adverse event | 0 | 0 | 2 |
| Withdrew: Symptomatic deterioration | 0 | 1 | 1 |
| Withdrew: Lack of compliance | 0 | 1 | 0 |
| Withdrew: Subject withdrawal of all treatment and follow-up with disagreement for contact | 0 | 1 | 0 |
| Withdrew: Death | 0 | 1 | 0 |
| Withdrew: Subject withdrawal of investigational product | 0 | 1 | 0 |
| Withdrew: Treating physician decision due to lack of clinical benefit for patient | 0 | 1 | 0 |
| Withdrew: Scans showed pd 01jul2019 (but the pt has received radiation and since ta05 the assessments are ne) | 0 | 1 | 0 |
Clinical benefit rate (CBR) at 24 weeks per investigator assessment. CBR is the proportion of patients with confirmed Complete Response (CR) or Partial Response (PR), or Stable Disease (SD) lasting 24 weeks.
| Participants | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Clinical Benefit Rate at 24 Weeks | 3 | 18 | 9 |
For assessment per Response Evaluation Criteria In Solid Tumors Guidelines (RECIST) v1.1, PFS is the time from the date of treatment start to the date of event defined as the first documented progression or death due to any cause.
| months | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Progression Free Survival (PFS) Per Investigator Assessment | 1.41 (1.38 to 1.45) | 5.52 (4.11 to 7.16) | 2.61 (1.45 to 2.73) |
For assessment per RECIST v1.1, PFS is the time from the date of treatment start to the date of event defined as the first documented progression or death due to any cause.
| months | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Progression Free Survival (PFS) Per Central Review | 1.41 (1.38 to 1.45) | 5.59 (4.11 to 7.39) | 1.45 (1.45 to 2.73) |
The proportion of patients with overall response of Complete Response or Partial Response based upon RECIST 1.1 (confirmed response).
| Participants | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Overall Response Rate (ORR) Per Investigator Assessment | 0 | 10 | 1 |
The proportion of patients with overall response of Complete Response or Partial Response based upon RECIST 1.1 (confirmed response).
| Participants | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Overall Response Rate (ORR) Per Central Review | 0 | 6 | 0 |
DoR applies only to patients with a Best Overall Response (BOR) of confirmed CR or PR (RECIST v1.1). For RECIST v1.1, DoR is defined as the time from the date of the first documented response (CR or PR) to the date of first documented progression, or death due to any cause.
| months | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Duration of Response (DoR) Per Investigator Assessment | — | 4.21 (2.79 to NA) | 4.50 |
DoR applies only to patients with a BOR of confirmed CR or PR (RECIST v1.1). For RECIST v1.1, DOR is defined as the time from the date of the first documented response (CR or PR) to the date of first documented progression, or death due to any cause.
| months | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Duration of Response (DoR) Per Central Review | — | 6.36 (4.17 to NA) | — |
The time from treatment start until death due to any cause.
| months | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Overall Survival (OS) | 14.09 (9.63 to NA) | 27.33 (19.94 to NA) | 26.41 (17.51 to NA) |
Evaluation of number of participants with Adverse Events leading to leading to discontinuation of study drug
| Participants | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Number of Patients With Adverse Events (AE's) Leading to Discontinuation of Study Drug | 0 | 1 | 3 |
AESIs for MCLA-128 combinations include: Infusion-related reactions (for any antibodies, known AESI for MCLA-128) Cardiotoxicity (anti-Human Epidermal Growth Factor Receptor (HER)2 therapy) Diarrhea (anti-HER2 therapy) Myelosuppression (vinorelbine)
| Participants | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Cardiotoxicity (anti-HER2 therapy) | 1 | 3 | 0 |
| Diarrhea (anti-HER2 therapy) | 7 | 28 | 17 |
| Infusion-related reaction | 1 | 7 | 12 |
| Myelosuppression (vinorelbine) | NA | 18 | NA |
Number of patients with anti-drug antibodies at baseline and on treatment
| Participants | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| Baseline, Anti-Drug Antibody (ADA)-Negative | 12 | 29 | 46 |
| Baseline, ADA-Positive | 3 | 9 | 3 |
| On-treatment, evaluable | 8 | 32 | 38 |
| On-treatment, ADA-Negative | 8 | 32 | 35 |
| On-treatment, ADA-Positive | 0 | 0 | 3 |
| Treatment-induced ADA | 0 | 0 | 3 |
| Treatment-boosted ADA | 0 | 0 | 0 |
Collected over During study treatment and up to 30 days after last administration of study drug (median duration of zenocutuzumab exposure was 6.0 weeks for Cohort 1 doublet, 19.3 weeks for Cohort 1 triplet and 11.8 weeks for Cohort 2).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1 Doublet | 0/15 (0%) | 2/15 (13.3%) | 15/15 (100%) |
| Cohort 1 Triplet | 1/39 (2.6%) | 8/39 (20.5%) | 39/39 (100%) |
| Cohort 2 | 1/50 (2%) | 9/50 (18%) | 48/50 (96%) |
| Event | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| PainGeneral disorders | 1/15 | 0/39 | 0/50 |
| ErysipelasInfections and infestations | 1/15 | 0/39 | 0/50 |
| AstheniaGeneral disorders | 0/15 | 2/39 | 0/50 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/15 | 2/39 | 0/50 |
| Infusion related reactionInjury, poisoning and procedural complications | 0/15 | 1/39 | 2/50 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/15 | 1/39 | 0/50 |
| DysphagiaGastrointestinal disorders | 0/15 | 1/39 | 0/50 |
| NauseaGastrointestinal disorders | 0/15 | 1/39 | 0/50 |
| VomitingGastrointestinal disorders | 0/15 | 1/39 | 0/50 |
| OsteomyelitisInfections and infestations | 0/15 | 1/39 | 0/50 |
| Event | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 |
|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 7/15 | 28/39 | 17/50 |
| NauseaGastrointestinal disorders | 3/15 | 18/39 | 14/50 |
| AstheniaGeneral disorders | 4/15 | 18/39 | 5/50 |
| NeutropeniaBlood and lymphatic system disorders | 0/15 | 17/39 | 0/50 |
| FatigueGeneral disorders | 5/15 | 13/39 | 11/50 |
| ConstipationGastrointestinal disorders | 2/15 | 12/39 | 6/50 |
| AnaemiaBlood and lymphatic system disorders | 0/15 | 11/39 | 1/50 |
| VomitingGastrointestinal disorders | 4/15 | 6/39 | 4/50 |
| Abdominal painGastrointestinal disorders | 1/15 | 9/39 | 6/50 |
| Mucosal inflammationGeneral disorders | 3/15 | 3/39 | 2/50 |
Treated subjects.
| Age, Categorical(Participants) | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 11 | 27 | 39 | 77 |
| >=65 years | 4 | 12 | 11 | 27 |
| Age, Continuous(years) | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 | Total |
|---|---|---|---|---|
| Mean | 53 ± 12.1 | 57 ± 12.0 | 57 ± 12.2 | 56 ± 12.1 |
| Sex: Female, Male(Participants) | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 | Total |
|---|---|---|---|---|
| Female | 15 | 39 | 50 | 104 |
| Male | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 | Total |
|---|---|---|---|---|
| Hispanic or Latino | 0 | 3 | 4 | 7 |
| Not Hispanic or Latino | 12 | 31 | 44 | 87 |
| Unknown or Not Reported | 3 | 5 | 2 | 10 |
| Race (NIH/OMB)(Participants) | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 3 | 0 | 4 |
| White | 9 | 22 | 46 | 77 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 5 | 14 | 4 | 23 |
| Region of Enrollment(participants) | Cohort 1 Doublet | Cohort 1 Triplet | Cohort 2 | Total |
|---|---|---|---|---|
| Netherlands | 1 | 2 | 1 | 4 |
| Belgium | 2 | 0 | 8 | 10 |
| United States | 2 | 8 | 6 | 16 |
| United Kingdom | 0 | 1 | 2 | 3 |
| France | 9 | 18 | 20 | 47 |
| Portugal | 0 | 7 | 6 | 13 |
| Spain | 1 | 3 | 7 | 11 |
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Lethal Congenital Contracture Syndrome 2