Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143

NCT ID: NCT04122625

Last Updated: 2023-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-04-26
• Study Completion Date: 2022-04-06

Brief Summary

Part A (dose-optimization)- to determine the recommended phase 2 dose (RP2D) taking into account dose-limiting toxicity (DLT/s) in Cycle 1, overall safety/tolerability and pharmacokinetic (PK), by optimizing doses of Debio 1143 when combined with the standard dose of nivolumab, as well as treatment compliance in participants with advanced solid malignancies who failed prior systemic standard treatments.

Part B (basket trial)- to evaluate the preliminary anti-tumor activity of Debio 1143 at the RP2D in combination with nivolumab at the standard dose, overall and in each participant cohort (Cohort 1: small cell lung cancer [SCLC]; Cohort 2: squamous cell carcinoma of the head and neck [SCCHN]; Cohort 3: gastrointestinal (GI) cancers with known microsatellite instability-high/mismatch repair deficiency (MSI-H/MMRd) or other deoxyribonucleic acid (DNA) damage repair (DDR) abnormalities, including homologous recombination deficiency (HRD); Cohort 4: platinum-resistant epithelial ovarian cancer [EOC], endometrial cancer, primary peritoneal cancer (PPC) or cervical cancer, with known MSIH/MMRd, hereditary/somatic mutations of the breast cancer 1 (BRCA1) and BRCA2 genes or other DNA DDR abnormalities (incl. HRD).

Conditions

Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A - Debio 1143 150 mg + Nivolumab

Participants received Debio 1143, 150 milligrams (mg) capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, intravenous (IV) infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Group Type: EXPERIMENTAL

Debio 1143

Intervention Type: DRUG

Administered as capsules.

Nivolumab

Intervention Type: DRUG

Administered as IV infusion.

Part A - Debio 1143 200 mg + Nivolumab

Participants received Debio 1143, 200 mg capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Group Type: EXPERIMENTAL

Debio 1143

Intervention Type: DRUG

Administered as capsules.

Nivolumab

Intervention Type: DRUG

Administered as IV infusion.

Part B - Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab

Participants with small-cell lung cancer (SCLC) received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Group Type: EXPERIMENTAL

Debio 1143

Intervention Type: DRUG

Administered as capsules.

Nivolumab

Intervention Type: DRUG

Administered as IV infusion.

Part B - Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab

Participants with squamous cell carcinoma of the head and neck (SCCHN) received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Group Type: EXPERIMENTAL

Debio 1143

Intervention Type: DRUG

Administered as capsules.

Nivolumab

Intervention Type: DRUG

Administered as IV infusion.

Part B - Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab

Participants with gastrointestinal (GI) cancers received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Group Type: EXPERIMENTAL

Debio 1143

Intervention Type: DRUG

Administered as capsules.

Nivolumab

Intervention Type: DRUG

Administered as IV infusion.

Part B - Cohort 4 (Gynecologic Cancers): Debio 1143 200 mg + Nivolumab

Participants with gynecologic cancers received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Group Type: EXPERIMENTAL

Debio 1143

Intervention Type: DRUG

Administered as capsules.

Nivolumab

Intervention Type: DRUG

Administered as IV infusion.

Interventions

Debio 1143

Administered as capsules.

Intervention Type: DRUG

Nivolumab

Administered as IV infusion.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Have received at least one prior line of standard systemic chemotherapy in the advanced/unresectable cancer setting (standard adjuvant/neoadjuvant treatment is acceptable if relapse occurred within six months of treatment end)
• Have progressed or relapsed during or after a prior anti-programmed cell death-1 (PD-1)/ programmed cell death-ligand 1 (PD-L1)-based treatment, given either as a single agent or in combination with standard/approved chemotherapy, tyrosine kinase inhibitors (TKIs), radiotherapy (RT) or other monoclonal antibodies (mAbs) that are not known to modulate/inhibit immune checkpoints (CPIs)
• Measurable disease (Part B only) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or Gynecologic Cancer Intergroup (GCIG) criteria in Cohort #4 of Part B (if applicable) and documented PD during or after prior PD-1/PD-L1 based therapy

Exclusion Criteria

• Thoracic or head and neck radiation >30 gray (Gy) within the 3 months prior to Cycle 1 Day 1 (C1D1)
• Have received, in total, more than 3 (i.e., Cohorts 1 & 2) or 4 (i.e., Cohorts 3 & 4) lines of prior systemic treatments in Part B (including adjuvant or neoadjuvant regimens if relapse within six months prior to C1D1)
• Liver cirrhosis Child-Pugh score B or C

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Debiopharm International SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Florida

Gainesville, Florida, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber/Partners Cancer Care

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

Montefiore Medical Center PRIME

The Bronx, New York, United States

UC Health, LLC.

Cincinnati, Ohio, United States

St. Luke's University Health Network

Bethlehem, Pennsylvania, United States

Methodist Hospital, Houston Methodist Cancer Center

Houston, Texas, United States

Georgetown University - Lombardi Comprehensive Cancer Center

Northwest, Washington, United States

Centre Leon Berard

Lyon, , France

Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Hospital Vall d'Hebron

Barcelona, , Spain

START Madrid, Fundacion Jimenez Diaz

Madrid, , Spain

START Madrid, H.U. Sanchinarro

Madrid, , Spain

Countries

United States; France; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-003546-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Debio 1143-106

Identifier Type: -

Identifier Source: org_study_id