A Phase 1/2 interventional study of MEN1611 and Cetuximab in Metastatic Colorectal Cancer, sponsored by Menarini Group. Completed at 28 sites in 7 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-05-01.
Sponsored by Menarini Group · Phase 1/2, Interventional, and Treatment
Open-label, dose-confirmation and cohort expansion, multicenter, Phase Ib/II study to assess the anti-tumor activity and safety of MEN1611 in combination with cetuximab for the treatment of participants with phosphatidylinositol 3-kinase, catalytic, alpha polypeptide gene (PIK3CA)-mutated metastatic colorectal cancer.
This Phase Ib/II study investigated the anti-tumor activity and safety of daily oral doses MEN1611 in combination with cetuximab in female and male participants affected by PIK3CA-mutated, neuroblastoma-Kristen-rat sarcoma virus (N-K-RAS) wild-type, and BRAF wild-type metastatic colorectal cancer.
MEN1611 is a potent, selective class I phosphoinositide 3-kinase (PI3K) inhibitor. The maximum tolerated dose of MEN1611 given as single agent was assessed in a Phase I trial in participants with advanced solid tumors.
This Phase Ib/II started with a dose confirmation part (Step 1) to identify the recommended phase 2 dose of MEN1611 given in combination with cetuximab.
The study continued with a cohort expansion (Step 2) to explore the anti-tumor activity of the selected MEN1611 dose level combined with cetuximab with further assessment of safety and tolerability.
6,541 studies on the registry are indexed under Colorectal Neoplasms; 1,667 are open to participants now.
This study's enrollment of 29 is below the median of 76 across 4,800 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →Menarini Group is the lead sponsor of 28 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Main Inclusion Criteria:
Main 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.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
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.
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.
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.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
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.
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.
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
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 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.
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.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
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.
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.
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.
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.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
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.
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.
HbA1c
A blood test of average blood sugar over the past two to three months, given as a percentage or in mmol/mol. 6.5% (48 mmol/mol) or more is the usual threshold for diabetes, normally confirmed by a second test.
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 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.
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.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MEN1611 + Cetuximab
Drug: MEN1611 · Drug: Cetuximab
Phase 1b: Recommended Phase 2 Dose (RP2D) of MEN1611 in Combination With Cetuximab
RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant during the dose confirmation phase (Phase 1b) experienced a dose-limiting toxicity (DLT) during the DLT assessment window (28 days), or the maximum dose judged to be tolerable by the data safety committee.
Time frame: Day 1 through Day 28 of Cycle 1 (28 days/cycle)
Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab
The best ORR was defined as percentage of participants who had a best overall response to therapy of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and was defined according to Response Evaluation Criteria in Solid Tumors version 1.1 assessment locally performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).
Time frame: Up to 37 Months
Phase 1b: Number of Participants With DLTs for MEN1611
A DLT was defined as any of the following adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during Cycle 1 over the DLT assessment window of 28 days: any Grade 3 (lasting \>7 days) or Grade 4 increase in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase; any Grade ≥3 cardiac disorder or new segmental wall-motion abnormalities; any Grade ≥3 non-hematologic toxicity with the following exceptions: nausea, vomiting, diarrhea, skin rash, hyperglycemia. An ADR was defined as any adverse event suspected by the investigator and/or the sponsor to be related to MEN1611, cetuximab, or both given in combination.
Time frame: Day 1 through Day 28 of Cycle 1 (28 days/cycle)
Plasma Concentration of MEN1611 in Combination With Cetuximab
Blood samples were taken for the analyses of MEN1611 in plasma at designated time points. Results are reported as nanograms/millilitre (ng/mL).
Time frame: Day 22 (1.5 hours postdose) of Cycle 1 (28 days/cycle)
Disease Control Rate (DCR) of MEN1611 in Combination With Cetuximab
DCR was defined as percentage of participants whose disease shrank or remained stable over a certain time period and was calculated based on the sum of the CR, PR, and SD rates according to local assessment.
Time frame: Up to 37 Months
Duration of Response (DOR) of MEN1611 in Combination With Cetuximab
DOR was defined as the time from confirmation of a PR, CR or SD as locally assessed, until the disease had been shown to progress following treatment. Participants with a previous response who did not show a relapse or died without recording a relapse were censored at their last available relapse-free tumor assessment date. Participants with only one tumor assessment after baseline showing a PD were not included in the calculation.
Time frame: Up to 37 months
Progression-free Survival (PFS) of MEN1611 in Combination With Cetuximab
PFS was defined as the number of days between the first study treatment administration to the date of first documented disease progression as per local assessment, relapse or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last tumor assessment date.
Time frame: Up to 37 months
Overall Survival (OS) of MEN1611 in Combination With Cetuximab
OS was defined as the number of days between the first study treatment administration and death from any cause. Participants still alive that had withdrawn from the study were censored using the latest among end of study and follow-up dates. Drop-out participants were considered censored and the last available date in which the participant was known to be alive was considered.
Time frame: Up to 37 months
| Milestone | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) |
|---|---|---|
| Started | 7 | 22 |
| Received at least 1 dose of study drug | 7 | 22 |
| Completed | 0 | 0 |
| Not completed | 7 | 22 |
| Withdrew: Withdrawal by subject | 0 | 3 |
| Withdrew: Death | 7 | 11 |
| Withdrew: Investigator decision | 0 | 7 |
| Withdrew: Lost to follow-up | 0 | 1 |
RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant during the dose confirmation phase (Phase 1b) experienced a dose-limiting toxicity (DLT) during the DLT assessment window (28 days), or the maximum dose judged to be tolerable by the data safety committee.
| mg | Phase 1b (Dose Confirmation) |
|---|---|
| Phase 1b: Recommended Phase 2 Dose (RP2D) of MEN1611 in Combination With Cetuximab | 48 |
The best ORR was defined as percentage of participants who had a best overall response to therapy of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and was defined according to Response Evaluation Criteria in Solid Tumors version 1.1 assessment locally performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).
| percentage of participants | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) |
|---|---|---|
| Complete Response | 0.0 | 7.1 |
| Partial Response | 40.0 | 7.1 |
| Stable Disease | 40.0 | 57.1 |
| Progressive Disease | 20.0 | 28.6 |
A DLT was defined as any of the following adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during Cycle 1 over the DLT assessment window of 28 days: any Grade 3 (lasting \>7 days) or Grade 4 increase in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase; any Grade ≥3 cardiac disorder or new segmental wall-motion abnormalities; any Grade ≥3 non-hematologic toxicity with the following exceptions: nausea, vomiting, diarrhea, skin rash, hyperglycemia. An ADR was defined as any adverse event suspected by the investigator and/or the sponsor to be related to MEN1611, cetuximab, or both given in combination.
| Participants | Phase 1b (Dose Confirmation) |
|---|---|
| Phase 1b: Number of Participants With DLTs for MEN1611 | 0 |
Blood samples were taken for the analyses of MEN1611 in plasma at designated time points. Results are reported as nanograms/millilitre (ng/mL).
| ng/mL | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) |
|---|---|---|
| Plasma Concentration of MEN1611 in Combination With Cetuximab | 173.37 ± 125.513 | 241.2 ± NA |
DCR was defined as percentage of participants whose disease shrank or remained stable over a certain time period and was calculated based on the sum of the CR, PR, and SD rates according to local assessment.
| percentage of participants | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) |
|---|---|---|
| Disease Control Rate (DCR) of MEN1611 in Combination With Cetuximab | 80 (28.4 to 99.5) | 71.4 (41.9 to 91.6) |
DOR was defined as the time from confirmation of a PR, CR or SD as locally assessed, until the disease had been shown to progress following treatment. Participants with a previous response who did not show a relapse or died without recording a relapse were censored at their last available relapse-free tumor assessment date. Participants with only one tumor assessment after baseline showing a PD were not included in the calculation.
| days | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) |
|---|---|---|
| Duration of Response (DOR) of MEN1611 in Combination With Cetuximab | 85 (47 to NA) | 169 (120 to NA) |
PFS was defined as the number of days between the first study treatment administration to the date of first documented disease progression as per local assessment, relapse or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last tumor assessment date.
| days | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) |
|---|---|---|
| Progression-free Survival (PFS) of MEN1611 in Combination With Cetuximab | 121 (75 to NA) | 162 (57 to 218) |
OS was defined as the number of days between the first study treatment administration and death from any cause. Participants still alive that had withdrawn from the study were censored using the latest among end of study and follow-up dates. Drop-out participants were considered censored and the last available date in which the participant was known to be alive was considered.
| days | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) |
|---|---|---|
| Overall Survival (OS) of MEN1611 in Combination With Cetuximab | 471 (171 to NA) | 308 (177 to NA) |
Collected over From Day 1 to the end of study (37 months). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Phase 1b (Dose Confirmation) | 7/7 (100%) | 5/7 (71.4%) | 7/7 (100%) |
| Phase 2 (Cohort Expansion) | 11/22 (50%) | 11/22 (50%) | 22/22 (100%) |
| Event | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) |
|---|---|---|
| Enterovesical fistulaGastrointestinal disorders | 1/7 | 0/22 |
| Acute kidney injuryRenal and urinary disorders | 1/7 | 0/22 |
| GastroenteritisInfections and infestations | 1/7 | 0/22 |
| HyperglycaemiaMetabolism and nutrition disorders | 1/7 | 1/22 |
| HypomagnesaemiaMetabolism and nutrition disorders | 1/7 | 0/22 |
| Abdominal painGastrointestinal disorders | 0/7 | 2/22 |
| CholangitisHepatobiliary disorders | 0/7 | 2/22 |
| HypotensionVascular disorders | 0/7 | 1/22 |
| Cardio-respiratory arrestCardiac disorders | 0/7 | 1/22 |
| AstheniaGeneral disorders | 0/7 | 1/22 |
| Event | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) |
|---|---|---|
| RashSkin and subcutaneous tissue disorders | 7/7 | 11/22 |
| DiarrhoeaGastrointestinal disorders | 5/7 | 16/22 |
| HyperglycaemiaMetabolism and nutrition disorders | 3/7 | 13/22 |
| AnaemiaBlood and lymphatic system disorders | 4/7 | 6/22 |
| FatigueGeneral disorders | 3/7 | 1/22 |
| ParonychiaInfections and infestations | 3/7 | 5/22 |
| HypomagnesaemiaMetabolism and nutrition disorders | 3/7 | 8/22 |
| AstheniaGeneral disorders | 0/7 | 9/22 |
| Mucosal inflammationGeneral disorders | 0/7 | 7/22 |
| NauseaGastrointestinal disorders | 1/7 | 7/22 |
Safety Population: all participants who received at least 1 dose of MEN1611.
| Age, Continuous(years) | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) | Total |
|---|---|---|---|
| Mean | 53.9 ± 12.16 | 58.9 ± 12.38 | 57.7 ± 12.31 |
| Sex: Female, Male(Participants) | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) | Total |
|---|---|---|---|
| Female | 1 | 11 | 12 |
| Male | 6 | 11 | 17 |
| Ethnicity (NIH/OMB)(Participants) | Phase 1b (Dose Confirmation) | Phase 2 (Cohort Expansion) | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 7 | 15 | 22 |
| Unknown or Not Reported | 0 | 7 | 7 |
PDFs hosted by the registry, ClinicalTrials.gov.
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Studies of the drug tested here: CH 5132799