Trial Outcomes & Findings for MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01) (NCT NCT04495621)

Last Updated: 2025-05-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

29 participants

Primary outcome timeframe

Day 1 through Day 28 of Cycle 1 (28 days/cycle)

Results posted on

2025-05-01

Participant Flow

Participant milestones

Participant milestones
Measure	Phase 1b (Dose Confirmation) Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.
Overall Study STARTED	7	22
Overall Study Received At Least 1 Dose of Study Drug	7	22
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	7	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1b (Dose Confirmation) Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.
Overall Study Withdrawal by Subject	0	3
Overall Study Death	7	11
Overall Study Investigator Decision	0	7
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1b (Dose Confirmation) n=7 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) n=22 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Total n=29 Participants Total of all reporting groups
Age, Continuous	53.9 years STANDARD_DEVIATION 12.16 • n=5 Participants	58.9 years STANDARD_DEVIATION 12.38 • n=7 Participants	57.7 years STANDARD_DEVIATION 12.31 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	11 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	15 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 28 of Cycle 1 (28 days/cycle)

Population: Safety Population: all participants who received at least 1 dose of MEN1611. As pre-specified, RP2D data were collected and are reported for 'Phase 1b (Dose Confirmation)' cohort only.

Outcome measures

Outcome measures
Measure	Phase 1b (Dose Confirmation) n=7 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.
Phase 1b: Recommended Phase 2 Dose (RP2D) of MEN1611 in Combination With Cetuximab	48 mg	—

PRIMARY outcome

Timeframe: Up to 37 Months

Population: Efficacy Population: all participants who received at least 2 complete treatment cycles and had at least 1 disease assessment.

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).

Outcome measures

Outcome measures
Measure	Phase 1b (Dose Confirmation) n=5 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) n=14 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.
Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab Complete Response	0.0 percentage of participants	7.1 percentage of participants
Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab Partial Response	40.0 percentage of participants	7.1 percentage of participants
Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab Stable Disease	40.0 percentage of participants	57.1 percentage of participants
Best Overall Response Rate (ORR) of MEN1611 in Combination With Cetuximab Progressive Disease	20.0 percentage of participants	28.6 percentage of participants

PRIMARY outcome

Timeframe: Day 1 through Day 28 of Cycle 1 (28 days/cycle)

Population: Dose-limiting Toxicity (DLT) Population: all participants who received at least 80% of MEN1611 and 75% of cetuximab during Cycle 1 with a safety follow-up of 28 days after the first administration of the study treatment. Any participant who experienced DLT was also considered evaluable, regardless of the dose received. As pre-specified, data were collected and reported for the 'Phase 1b (Dose Confirmation)' cohort only.

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.

Outcome measures

Outcome measures
Measure	Phase 1b (Dose Confirmation) n=6 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.
Phase 1b: Number of Participants With DLTs for MEN1611	0 Participants	—

SECONDARY outcome

Timeframe: Day 22 (1.5 hours postdose) of Cycle 1 (28 days/cycle)

Population: Pharmacokinetics (PK) Set: all participants who received MEN1611 and for whom a PK sample was obtained and analyzed. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.

Blood samples were taken for the analyses of MEN1611 in plasma at designated time points. Results are reported as nanograms/millilitre (ng/mL).

Outcome measures

Outcome measures
Measure	Phase 1b (Dose Confirmation) n=7 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) n=1 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.
Plasma Concentration of MEN1611 in Combination With Cetuximab	173.37 ng/mL Standard Deviation 125.513	241.2 ng/mL Standard Deviation NA Standard deviation is not calculable for 1 participant.

SECONDARY outcome

Timeframe: Up to 37 Months

Population: Efficacy Population: all participants who received at least 2 complete treatment cycles and had at least 1 disease assessment.

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.

Outcome measures

Outcome measures
Measure	Phase 1b (Dose Confirmation) n=5 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) n=14 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.
Disease Control Rate (DCR) of MEN1611 in Combination With Cetuximab	80 percentage of participants Interval 28.4 to 99.5	71.4 percentage of participants Interval 41.9 to 91.6

SECONDARY outcome

Timeframe: Up to 37 months

Population: Efficacy Population: all participants who received at least 2 complete treatment cycles and had at least 1 disease assessment. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Phase 1b (Dose Confirmation) n=4 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) n=10 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.
Duration of Response (DOR) of MEN1611 in Combination With Cetuximab	85 days Interval 47.0 to Values were non-estimable (insufficient number of participants with events).	169 days Interval 120.0 to Values were non-estimable (insufficient number of participants with events).

SECONDARY outcome

Timeframe: Up to 37 months

Population: Efficacy Population: all participants who received at least 2 complete treatment cycles and had at least 1 disease assessment.

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.

Outcome measures

Outcome measures
Measure	Phase 1b (Dose Confirmation) n=5 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) n=14 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.
Progression-free Survival (PFS) of MEN1611 in Combination With Cetuximab	121 days Interval 75.0 to Values were non-estimable (insufficient number of participants with events).	162 days Interval 57.0 to 218.0

SECONDARY outcome

Timeframe: Up to 37 months

Population: Efficacy Population: all participants who received at least 2 complete treatment cycles and had at least 1 disease assessment.

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.

Outcome measures

Outcome measures
Measure	Phase 1b (Dose Confirmation) n=5 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) n=14 Participants Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.
Overall Survival (OS) of MEN1611 in Combination With Cetuximab	471 days Interval 171.0 to Values were non-estimable (insufficient number of participants with events).	308 days Interval 177.0 to Values were non-estimable (insufficient number of participants with events).

Adverse Events

Phase 1b (Dose Confirmation)

Serious events: 5 serious events

Other events: 7 other events

Deaths: 7 deaths

Phase 2 (Cohort Expansion)

Serious events: 11 serious events

Other events: 22 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Sciences

Menarini Ricerche S.p.A.

Phone: +39 0555680

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The results of the study cannot be submitted for presentation, abstract, poster exhibition, or publication by the investigator until Menarini Ricerche S.p.A. has reviewed/commented and agreed to any publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Phase 1b (Dose Confirmation) n=7 participants at risk Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.	Phase 2 (Cohort Expansion) n=22 participants at risk Participants received MEN1611 twice daily and cetuximab weekly, every 28-day cycle.
Vascular disorders Hypotension	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
General disorders Asthenia	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
General disorders Pyrexia	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Gastrointestinal disorders Abdominal pain	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	9.1% 2/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Gastrointestinal disorders Constipation	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Gastrointestinal disorders Diarrhoea	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Gastrointestinal disorders Enterovesical fistula	14.3% 1/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	0.00% 0/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Gastrointestinal disorders Gastrointestinal necrosis	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Hepatobiliary disorders Cholangitis	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	9.1% 2/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Renal and urinary disorders Acute kidney injury	14.3% 1/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	0.00% 0/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Musculoskeletal and connective tissue disorders Fistula	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Infections and infestations Anal abscess	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Infections and infestations Biliary tract infection	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Infections and infestations Gastroenteritis	14.3% 1/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	0.00% 0/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Infections and infestations Influenza	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Infections and infestations Sepsis	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Infections and infestations Staphylococcal infection	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Metabolism and nutrition disorders Hyperglycaemia	14.3% 1/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	4.5% 1/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.
Metabolism and nutrition disorders Hypomagnesaemia	14.3% 1/7 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.	0.00% 0/22 • From Day 1 to the end of study (37 months) All reported safety data based upon the Safety Population: all participants who received at least 1 dose of MEN1611.