Trial Title:
M9466 in Combination With Topoisomerase 1 Inhibitors-based Regimens in Advanced Solid Tumors and Colorectal Cancer (DDRiver 511)
NCT ID:
NCT06509906
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Colorectal Neoplasms
Leucovorin
Folic Acid
Bevacizumab
Fluorouracil
Irinotecan
Levoleucovorin
Conditions: Keywords:
PARP inhibitor
DNA repair inhibitor
Irinotecan
FOLFIRI
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
M9466
Description:
M9466 will be administered orally until progressive disease, unacceptable toxicity,
death, or end of study.
Arm group label:
M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts)
Arm group label:
M9466 + Irinotecan (Run-in Cohort)
Other name:
HRS-1167
Intervention type:
Drug
Intervention name:
Irinotecan
Description:
Irinotecan will be administered intravenously once every 2 weeks (q2w) until progressive
disease, unacceptable toxicity, death, or end of study.
Arm group label:
M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts)
Arm group label:
M9466 + Irinotecan (Run-in Cohort)
Intervention type:
Drug
Intervention name:
Folinic acid
Description:
Folinic acid will be administered intravenously q2w as per standard of care.
Arm group label:
M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts)
Other name:
Calcium folinate Leucovorin
Intervention type:
Drug
Intervention name:
Fluorouracil (5-FU)
Description:
Fluorouracil will be administered intravenously as per standard of care.
Arm group label:
M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts)
Other name:
5-FU
Intervention type:
Drug
Intervention name:
Bevacizumab
Description:
Bevacizumab will be administered intravenously, q2w until progressive disease,
unacceptable toxicity, death, or end of study.
Arm group label:
M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts)
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.
Criteria for eligibility:
Criteria:
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
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sarah Cannon Research Institute at Health One
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Carolina BioOncology Institute, LLC - Cancer Therapy and Research Center
Address:
City:
Pennington
Zip:
08534
Country:
United States
Status:
Recruiting
Facility:
Name:
Vanderbilt University - 150912667
Address:
City:
Nashville
Zip:
37232
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
The University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030-4009
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Cancer Research SA
Address:
City:
Elizabeth Vale
Country:
Australia
Status:
Not yet recruiting
Facility:
Name:
St George Private Hospital
Address:
City:
Kogarah
Country:
Australia
Status:
Not yet recruiting
Contact:
Phone:
888-275-7376
Email:
eMediUSA@emdserono.com
Facility:
Name:
Peter MacCallum Cancer Centre - Use the one with Account 2 VCCC
Address:
City:
Parkville
Country:
Australia
Status:
Not yet recruiting
Contact:
Phone:
+49 6151 72 5200
Email:
service@emdgroup.com
Facility:
Name:
National Cancer Center Hospital
Address:
City:
Chuo-ku
Country:
Japan
Status:
Not yet recruiting
Facility:
Name:
Samsung Medical Center
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Not yet recruiting
Facility:
Name:
Seoul National University Hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Not yet recruiting
Facility:
Name:
NEXT Barcelona - NEXT Barcelona
Address:
City:
Barcelona
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
NEXT Madrid - Hospital Universitario Quironsalud Madrid
Address:
City:
Pozuelo de Alarcon
Country:
Spain
Status:
Not yet recruiting
Start date:
October 8, 2024
Completion date:
April 7, 2026
Lead sponsor:
Agency:
EMD Serono Research & Development Institute, Inc.
Agency class:
Industry
Collaborator:
Agency:
Merck KGaA, Darmstadt, Germany
Agency class:
Industry
Source:
EMD Serono
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06509906
https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS202650_0001
