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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06509906




Registration number
NCT06509906
Ethics application status
Date submitted
15/07/2024
Date registered
19/07/2024
Date last updated
12/11/2024

Titles & IDs
Public title
M9466 in Combination With Topoisomerase 1 Inhibitors-based Regimens in Advanced Solid Tumors and Colorectal Cancer (DDRiver 511)
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)
Secondary ID [1] 0 0
2024-514155-15-00
Secondary ID [2] 0 0
MS202650_0001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - M9466
Treatment: Drugs - Irinotecan
Treatment: Drugs - Folinic acid
Treatment: Drugs - Fluorouracil (5-FU)
Treatment: Drugs - Bevacizumab

Experimental: M9466 + Irinotecan (Run-in Cohort) -

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


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

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

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

Treatment: Drugs: Fluorouracil (5-FU)
Fluorouracil will be administered intravenously as per standard of care.

Treatment: Drugs: Bevacizumab
Bevacizumab will be administered intravenously, q2w until progressive disease, unacceptable toxicity, death, or end of study.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs
Timepoint [1] 0 0
Time from signing Informed Consent Form (ICF) up to 30 days after end of study intervention (approximately assessed up to 18.7 months)
Primary outcome [2] 0 0
Number of Participants with Dose Limiting Toxicity (DLT)
Timepoint [2] 0 0
Day 1 up to Day 28 of the first two Cycles (each cycle is of 14 days)
Secondary outcome [1] 0 0
Pharmacokinetic (PK) Plasma Concentration of M9466
Timepoint [1] 0 0
Pre-dose up to 6 hours post-dose on Cycle 1 Day 1; at pre-dose on Cycle 1 Day 5 and Cycle 1 Day 8 (each cycle is of 14 days)
Secondary outcome [2] 0 0
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) Assessed by Investigator
Timepoint [2] 0 0
Time from first treatment of study intervention up to planned assessment at 18.7 months

Eligibility
Key inclusion criteria
* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/10/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
7/04/2026
Actual
Sample size
Target
54
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Cancer Research SA - Elizabeth Vale
Recruitment hospital [2] 0 0
St George Private Hospital - Kogarah
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Use the one with Account 2 VCCC - Parkville
Recruitment postcode(s) [1] 0 0
- Elizabeth Vale
Recruitment postcode(s) [2] 0 0
- Kogarah
Recruitment postcode(s) [3] 0 0
- Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
New Jersey
Country [3] 0 0
United States of America
State/province [3] 0 0
Tennessee
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Japan
State/province [5] 0 0
Chuo-ku
Country [6] 0 0
Korea, Republic of
State/province [6] 0 0
Seoul
Country [7] 0 0
Spain
State/province [7] 0 0
Barcelona
Country [8] 0 0
Spain
State/province [8] 0 0
Pozuelo de Alarcon

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
EMD Serono Research & Development Institute, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT06509906
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
EMD Serono Research & Development Institute, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US Medical Information
Address 0 0
Country 0 0
Phone 0 0
888-275-7376
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06509906