Trial purpose
Cancer treatment
Tumor type
Multi-Cancer
Age
18+
Clinical summary
Summary
The purpose of this study is to evaluate the safety and preliminary clinical activity of a targeted drug called M9466, which is a PARP1 inhibitor, when given in combination with other medicines.
The study has two cohorts.
M9466 + Irinotecan Run-in Cohort: Will enrol people with locally advanced or metastatic solid cancers that aren't responding to other treatments, or have no standard treatments available. They will receive M9466 orally plus Irinotecan chemotherapy intravenously (IV) every 2 weeks.
M9466 + FOLFIRI + Bevacizumab Dose Finding Cohorts: Will enrol people with locally advanced or metastatic colorectal cancer who haven't responded to or progressed on prior treatment for their advanced/metastatic disease. They will receive M9466 orally, irinotecan chemotherapy IV every 2 weeks, folinic acid IV every 2 weeks, 5-FU chemotherapy IV and Bevacizumab targeted therapy IV every 2 weeks.
Conditions
This trial is treating people with locally advanced or metastatic solid cancers and bowel cancer
Eligibility
Inclusion
- 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; Cetuximab and encorafenib ± binimetinib, 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
- Other protocol defined inclusion criteria could apply
Exclusion
- 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)
- Participant has a history of 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
- Other protocol defined exclusion criteria could apply
Inclusion
- Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
- You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
Exclusion
- You have been diagnosed with a prior or secondary type of cancer.
- You have certain types of non-cancer medical conditions.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ClinicalTrials.gov, EU Clinical Trials Register *. View further details about this trial on the registry via the links below:
Trial sponsor
EMD Serono Research & Development Institute, Inc.
Scientific Title
An Open Label, Multicenter, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of the PARP1 Inhibitor M9466 in Combination With Topoisomerase 1 Inhibitor-based Regimens in Advanced Solid Tumors and Colorectal Cancer (DDRiver 511)
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