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

Part of paid clinical trials in Gainesville, Florida.

Sponsor
Debiopharm International SA
Study ID
NCT04122625
Phase
PHASE1/PHASE2
Status
Completed

Conditions

  • Solid Tumor

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Debio 1143 — DRUG
    Administered as capsules.
  • Nivolumab — DRUG
    Administered as IV infusion.

Study Details

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).

Key Dates

Start date
Apr 26, 2019
Status verified
May 2023
Primary completion
Apr 6, 2022
Completion
Apr 6, 2022

Study Design

Enrollment
46 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.

Primary Outcome Measure

Part A: Number of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: Part A: Cycle 1 (28 days) ]

Locations (11)

FacilityCityStateZIPSite coordinators
University of FloridaGainesvilleFlorida32611-
H. Lee Moffitt Cancer Center and Research InstituteTampaFlorida33612-9497-
Rush University Medical CenterChicagoIllinois60612-
Beth Israel Deaconess Medical CenterBostonMassachusetts02215-
Dana-Farber/Partners Cancer CareBostonMassachusetts02215-
Washington UniversitySt LouisMissouri63110-
Montefiore Medical Center PRIMEThe BronxNew York10461-
UC Health, LLC.CincinnatiOhio45229-
St. Luke's University Health NetworkBethlehemPennsylvania18015-
Methodist Hospital, Houston Methodist Cancer CenterHoustonTexas77030-
Georgetown University - Lombardi Comprehensive Cancer CenterNorthwestWashington20007-

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By research site
University of Florida· Gainesville, FLH. Lee Moffitt Cancer Center and Research Institute· Tampa, FLRush University Medical Center· Chicago, ILBeth Israel Deaconess Medical Center· Boston, MADana-Farber/Partners Cancer Care· Boston, MAWashington University· St Louis, MO

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