NCT04122625|CompletedPhase 1ResultsDMCFDA Drug

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

SMARTPLUS-106

A Dose-optimization, Exploratory Phase Ib/II Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143, When Given in Combination With the Anti-PD-1 Antibody Nivolumab in Patients With Specific Solid Tumors Who Have Progressed During or Immediately After Anti-PD-1/PD-L1 Treatment

Debiopharm International SA ClinicalTrials.gov

Compare

2 other identifiers

Debio 1143-1062018-003546-16

Study Type

interventional

Target

Locations

3 countries

Sites

Timeline

RegisteredOct 2019

StartedApr 2019

CompletionApr 2022

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).

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P50-P75 for phase_1

Timeline

Completed

Started Apr 2019

Typical duration for phase_1

Geographic Reach

3 countries

17 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

2.9 years study duration

Study Start

First participant enrolled

April 26, 2019

Completed

4 months until next milestone

First Submitted

Initial submission to the registry

August 30, 2019

Completed

1 month until next milestone

First Posted

Study publicly available on registry

October 10, 2019

Completed

2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 6, 2022

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 6, 2022

Completed

1.2 years until next milestone

Results Posted

Study results publicly available

June 12, 2023

Completed

Last Updated

June 12, 2023

Status Verified

May 1, 2023

Enrollment Period

2.9 years

First QC Date

August 30, 2019

Results QC Date

April 5, 2023

Last Update Submit

May 17, 2023

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

Part A: Number of Participants With Dose-limiting Toxicities (DLTs)
DLT: any of following treatment-emergent adverse events (TEAEs) as per NCI CTCAE Grade V5.0 Criteria (Grades 1=mild, 2=moderate, 3=severe and 4 or 5= life-threatening/fatal outcomes) which are possibly, probably or definitely related to combination treatment and occurring in Cycle 1 (1 Cycle=28 days): Any Grade 4 or 5 hematologic toxicity, clinical or laboratory non-hematologic toxicity; febrile neutropenia any grade, Grade 3 thrombocytopenia if associated with bleeding or requiring platelet transfusion; Grade 2; Grade 3 and any other Grade 3 non-hematologic, treatment-related clinical toxicity lasting ≥3 days; delay of \>2 weeks due to drug-related toxicity in initiating Cycle 2; unable to complete at least 70% of the scheduled treatment (\>six Debio 1143 skipped doses in Cycle 1) due to treatment-related toxicity; required dose reduction in Cycle 1 or on Cycle 2 Day 1 or requirement for treatment withdrawal due to treatment-related toxicity (even if not meeting other DLT criteria).
Part A: Cycle 1 (28 days)
Part B: Confirmed Objective Response Rate (ORR)
ORR was determined per response evaluation criteria in solid tumors (RECIST) v1.1 and/or gynecologic cancer intergroup (GCIG) criteria (for Cohort 4). ORR was calculated as the percentage of participants with a confirmed objective response. A confirmed objective response is a confirmed best overall response of partial response (PR) or complete response (CR) recorded after the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first. CR is defined by the disappearance of all target lesions and reduction of any pathological lymph nodes in short axis to \<10 millimeters (mm). PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.
Part B: From the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first (up to approximately 2.05 years)

Secondary Outcomes (25)

Parts A and B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Including Laboratory Abnormalities Reported as TEAEs, and Serious Adverse Events (SAEs)
From the first study drug administration and up to 5 months after last nivolumab infusion, or the earliest date of new anticancer therapy -1 day, whichever occurs first (up to approximately 2.08 years in Part A and 2.05 years in Part B)
Parts A and B: Change From Baseline in Weight
From Baseline up to end of treatment (up to approximately 1.53 years in Part A and up to 1 year in Part B)
Parts A and B: Number of Participants With Markedly Abnormal Change From Baseline in Vital Signs
From Baseline up to end of treatment (up to approximately 1.53 years in Part A and up to 1 year in Part B)
Parts A and B: Number of Participants With Change From Baseline in Temperature Reported as TEAEs
From Baseline up to end of treatment (up to approximately 1.53 years in Part A and up to 1 year in Part B)
Parts A and B: Number of Participants With Markedly Abnormal Change From Baseline in Electrocardiogram (ECG) Readings
From Baseline up to end of treatment (up to approximately 1.53 years in Part A and up to 1 year in Part B)
+20 more secondary outcomes

Study Arms (6)

Part A - Debio 1143 150 mg + Nivolumab

EXPERIMENTAL

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.