Phase 2
Completed N=11
Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143
Source: ClinicalTrials.gov NCT04122625 ↗Enrolled (actual)
11
Serious AEs
52.2%
Results posted
Jun 2023
Primary outcomePrimary: Part A: Number of Participants With Dose-limiting Toxicities (DLTs) — 0; 0 Participants
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Number of Participants With Dose-limiting Toxicities (DLTs) |
0; 0 | — |
| PRIMARY Part B: Confirmed Objective Response Rate (ORR) |
0.0; 0.0; 0.0; 9.1 | — |
| SECONDARY Parts A and B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Including Laboratory Abnormalities Reported as TEAEs, and Serious Adverse Events (SAEs) |
3; 8; 8; 8; 8; 11 | — |
| SECONDARY Parts A and B: Change From Baseline in Weight |
-5.57; -10.00; -4.33; -4.00; -0.80; -1.11 | — |
| SECONDARY Parts A and B: Number of Participants With Markedly Abnormal Change From Baseline in Vital Signs |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Parts A and B: Number of Participants With Change From Baseline in Temperature Reported as TEAEs |
0; 2; 1; 1; 0; 3 | — |
| SECONDARY Parts A and B: Number of Participants With Markedly Abnormal Change From Baseline in Electrocardiogram (ECG) Readings |
0; 3; 1; 1; 2; 0 | — |
| SECONDARY Parts A and B: Number of Participants With Shift From Baseline to Worst On-Treatment Value in Eastern Cooperative Oncology Group Performance Status (ECOG-PS) |
1; 3; 0; 2; 1; 1 | — |
| SECONDARY Parts A and B: Number of Participants With TEAEs Including Laboratory Abnormalities Leading to Treatment Discontinuations and Dose Modifications |
1; 1; 0; 3; 1; 2 | — |
| SECONDARY Part A: Confirmed Objective Response Rate (ORR) |
0.0; 12.5 | — |
| SECONDARY Parts A and B: Unconfirmed Objective Response Rate (uORR) |
0.0; 25.0; 0.0; 0.0; 0.0; 9.1 | — |
| SECONDARY Parts A and B: Disease Control Rate (DCR) |
66.7; 50.0; 25.0; 75.0; 37.5; 45.5 | — |
| SECONDARY Parts A and B: Median Duration of Response (DOR) |
NA; NA | — |
| SECONDARY Parts A and B: Progression Free Survival (PFS) |
2.3; 2.3; 1.8; 1.9; 1.2; 1.8 | — |
| SECONDARY Parts A and B: PFS Rate at Months 6 and 12 |
0.0; 0.2; 0.1; 0.0; 0.1; 0.2 | — |
| SECONDARY Parts A and B: Overall Survival (OS) |
13.8; NA; 17.5; 4.7; 5.2; 11.7 | — |
| SECONDARY Parts A and B: OS Rate at Months 12 and 18 |
1.0; 0.5; 0.9; 0.3; 0.4; 0.4 | — |
| SECONDARY Part A: Area Under the Curve From Time 0 to 4 Hours (AUC0-4H) of Debio 1143 and Debio 1143-MET1 |
6200.28; 4907.15; 4321.40; 5861.53; 5081.21; 5114.03 | — |
| SECONDARY Part B: AUC0-4H of Debio 1143 and Debio 1143-MET1 |
6842.88; 5552.70; 5149.10; 7619.75; 7167.67; 5668.59 | — |
| SECONDARY Part A: Area Under the Curve From Time 0 to 8 Hours (AUC0-8H) of Debio 1143 and Debio 1143-MET1 |
8954.45; 8497.84; 6699.18; 9437.55; 7280.65; 8024.00 | — |
| SECONDARY Part A: Maximum Observed Concentration (Cmax) of Debio 1143 and Debio 1143-MET1 |
3063.33; 2020.63; 1656.67; 2132.71; 2426.67; 1956.29 | — |
| SECONDARY Part B: Cmax of Debio 1143 and Debio 1143-MET1 |
2839.5; 2266.1; 2331.3; 2850.0; 2786.3; 2065.8 | — |
| SECONDARY Part A: Trough Concentration (Cmin) of Debio 1143 and Debio 1143-MET1 |
113.10; 169.50; 118.27; 173.35; 7.34; 5.22 | — |
| SECONDARY Part B: Trough Concentration (Cmin) of Debio 1143 and Debio 1143-MET1 |
198.05; 167.20; 192.86; 143.39; 150.29; 221.60 | — |
| SECONDARY Part A: Serum Trough Concentration of Nivolumab |
21366.67; 22271.43; 43500.00; 32700.00; 27100.00 | — |
| SECONDARY Part B: Serum Trough Concentration of Nivolumab |
21312.5; 25414.3; 33725.0; 22332.0; 34100.0; 40600.0 | — |
| SECONDARY Parts A and B: Time to Response (TTR) |
82; 52 | — |
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
Data sourced from ClinicalTrials.gov (NCT04122625). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.