M9466 in Combination With Topoisomerase 1 Inhibitors-based Regimens in Advanced Solid Tumors and Colorectal Cancer (DDRiver 511)

NCT06509906 | Terminated Phase 1 FDA Drug

• 2 other identifiers: MS202650_00012024-514155-15-00
• Study Type: interventional
• Target: 3
• Locations: 5 countries
• Sites: 12

Brief Summary

The purpose of this study is to evaluate the safety and preliminary clinical activity of M9466 in combination with topoisomerase 1 inhibitors-based regimens. As such the combination with FOLFIRI (folinic acid, fluorouracil, irinotecan) and Bevacizumab will be evaluated in participants with colorectal cancer, to establish the M9466 maximum tolerated dose if observed and the recommended dose for expansion. Study Duration: After a Screening period of up to 28 days, enrolled participants will remain in the study until they have completed all the study visits or until they withdraw consent, are lost to follow-up, or die. Visit Frequency: The participants will come for a Screening Visit and 1 to 2 visits per treatment cycle. After end of study intervention period, the participants will come for an End of Treatment Visit and a Safety Follow-up Visit.

Conditions

Advanced Solid Tumor

Keywords

PARP inhibitor; DNA repair inhibitor; Irinotecan; FOLFIRI

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs

  Time from signing Informed Consent Form (ICF) up to 30 days after end of study intervention (approximately assessed up to 18.7 months)

• Number of Participants with Dose Limiting Toxicity (DLT)

  Day 1 up to Day 28 of the first two Cycles (each cycle is of 14 days)

Secondary Outcomes (2)

• Pharmacokinetic (PK) Plasma Concentration of M9466

  Pre-dose up to 6 hours post-dose on Cycle 1 Day 1; (each cycle is of 14 days)

• Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) Assessed by Investigator

  Time from first treatment of study intervention up to planned assessment at 18.7 months

Study Arms (2)

M9466 + Irinotecan (Run-in Cohort)

EXPERIMENTAL

Drug: M9466; Drug: Irinotecan; Drug: Granulocyte colony stimulating factor (G-CSF)

M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts)

EXPERIMENTAL

Drug: M9466; Drug: Irinotecan; Drug: Folinic acid; Drug: Fluorouracil (5-FU); Drug: Bevacizumab; Drug: Granulocyte colony stimulating factor (G-CSF)

Interventions

Folinic acid DRUG

Folinic acid will be administered intravenously q2w as per standard of care.

Also known as: Calcium folinate Leucovorin

M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts)

Fluorouracil (5-FU) DRUG

Fluorouracil will be administered intravenously as per standard of care.

Also known as: 5-FU

M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts)

Bevacizumab DRUG

Bevacizumab will be administered intravenously, q2w until progressive disease, unacceptable toxicity, death, or end of study.

M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts)

Granulocyte colony stimulating factor (G-CSF) DRUG

G-CSF will be administered subcutaneously at every cycle of study intervention as per standard of care.

M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts); M9466 + Irinotecan (Run-in Cohort)

M9466 DRUG

M9466 will be administered orally until progressive disease, unacceptable toxicity, death, or end of study.

Also known as: HRS-1167

M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts); M9466 + Irinotecan (Run-in Cohort)

Irinotecan DRUG

Irinotecan will be administered intravenously once every 2 weeks (q2w) until progressive disease, unacceptable toxicity, death, or end of study.

M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts); M9466 + Irinotecan (Run-in Cohort)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• M9466 + Irinotecan Run-in Cohort: Participants with locally advanced or metastatic disease that is refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator (that is \[i.e.\] participants who have exhausted all standard of care (SoC) options according to International Guidelines), and who may derive clinical benefit from the combination treatment with M9466 and irinotecan
• M9466 + FOLFIRI + Bevacizumab Dose Finding Cohorts: Participants with documented histopathological diagnosis of locally advanced or metastatic colorectal cancer (CRC), who were intolerant/refractory to or progressed after standard systemic therapies for the advanced/metastatic stage that included: Oxaliplatin and a fluoropyrimidine (administration in the adjuvant setting fulfills this criterion if progression occurred within 12 months of the last dose). Prior use of irinotecan is permitted; Either an anti- epidermal growth factor receptor (anti-EGFR) or an anti- Vascular endothelial growth factor (anti-VEGF) agent (not applicable if oxaliplatin was administered in the adjuvant setting); An immune checkpoint inhibitor for participants with known MSI-H status; Anti-EGFR agent and BRAF tyrosine kinase inhibitor ± MEK inhibitor, if locally available, for participants with BRAF V600E mutations. Participants may have received maximally 1 previous regimen for the treatment of metastatic disease (with the exception of participants with MSI-H disease or BRAF positive disease who are allowed to have had up to 2 previous lines of treatment)
• Eastern Cooperative Oncology Group performance status (ECOG PS) less than or equal to (\<=) 1

You may not qualify if:

• Persistence of AEs related to any prior treatments that have not recovered to Grade \<= 1 by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0) unless AEs are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator (for example \[e.g.\] neuropathy or alopecia)
• History of additional malignancy within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertrophy, or malignancy that in the opinion of the Investigator, is considered cured with minimal risk of recurrence within 3 years). Participants with history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) are excluded, irrespective of timeframe
• Participant with known polymorphisms in UGT1A1, DPYD or other enzymes known to predict for increased toxicity from irinotecan or 5 fluorouracil (5-FU) should be excluded; if status is unknown testing is not mandated, unless required by local guidance. Participants that discontinued prior 5-FU treatment due to toxicity are also excluded
• Participants with known brain metastases, except if clinically controlled, which is defined as individuals with central nervous system (CNS) tumors that have been treated and are asymptomatic, and who have discontinued steroids (for the treatment of CNS tumors) for \> 28 days prior to first dose of study intervention

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (12)

Sarah Cannon Research Institute at Health One

Denver, Colorado, 80218, United States

Location

Carolina BioOncology Institute, LLC - Cancer Therapy and Research Center

Pennington, New Jersey, 08534, United States

Location

Vanderbilt University - 150912667

Nashville, Tennessee, 37232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Cancer Research SA

Elizabeth Vale, Australia

Location

St George Private Hospital

Kogarah, Australia

Location

Peter MacCallum Cancer Centre - Use the one with Account 2 VCCC

Parkville, Australia

Location

National Cancer Center Hospital

Chūōku, Japan

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

NEXT Barcelona - NEXT Barcelona

Barcelona, Spain

Location

NEXT Madrid - Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Spain

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Interventions

Irinotecan; Leucovorin; Fluorouracil; Bevacizumab; Granulocyte Colony-Stimulating Factor

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Medical Responsible

  EMD Serono Research & Development Institute, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2024
• First Posted: July 19, 2024
• Study Start: October 8, 2024
• Primary Completion: December 2, 2025
• Study Completion: December 2, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); AU (3); JP (1); US (4); KR (2)