Description:
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).
Title
- Brief Title: Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
Debio 1143-106
- SECONDARY ID:
2018-003546-16
- NCT ID:
NCT04122625
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Debio 1143 | | Debio 1143 + Nivolumab |
Nivolumab | | Debio 1143 + Nivolumab |
Purpose
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 Arms
Name | Type | Description | Interventions |
---|
Debio 1143 + Nivolumab | Experimental | Part A: Participants will receive Debio 1143 at a starting dose of 150 milligrams (mg) orally once daily on Days 1-10 and Days 15-24 every 4 weeks (q4w) along with nivolumab at a flat dose of 240 mg intravenously (IV) on Days 1 and 15 of a 28-day cycle, participants may be switched to 480 mg IV on Day 1 q4w, exclusively upon investigator request with the sponsor agreement. Part B: Participants will receive Debio 1143 at RP2D established in Part A in combination with nivolumab as per standard care. | |
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 (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 (including adjuvant or neoadjuvant regimens if relapse
within six months prior to C1D1)
- Liver cirrhosis Child-Pugh score B or C
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Part A: Recommended Phase 2 Dose (RP2D) of Debio1143 |
Time Frame: | Up to 28 days (Cycle 1) |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Part A and B: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Laboratory Abnormalities |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Number of Participants with Change in Weight |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Number of Participants with Change in Vital Signs |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Number of Participants with Change in Temperature |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Number of Participants with Change in Electrocardiogram (ECG) |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Number of Participants with Change in Eastern Cooperative Oncology Group performance status (ECOG-PS) |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Number of Participants Leading to Treatment Discontinuations and Treatment Modifications due to AEs and Laboratory Abnormalities |
Time Frame: | Up to 17 months |
Safety Issue: | |
Description: | |
Measure: | Part A: Confirmed Objective Response Rate (ORR) |
Time Frame: | From first occurrence of objective response until disease progression or death from any cause or end of study (Up to 17 months) |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Unconfirmed Objective Response Rate (ORR) |
Time Frame: | From first occurrence of objective response until disease progression or death from any cause or end of study (Up to 17 months) |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Disease Control Rate (DCR) |
Time Frame: | From the start of study treatment until disease progression/recurrence or analysis cut-off, whichever occurs first (Up to 17 months) |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Time to Response (TTR) |
Time Frame: | From the date of first dose to the date of the first documented evidence of response (Up to 17 months) |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Duration of Response (DOR) |
Time Frame: | From the time of documentation of response to disease progression or analysis cut-off date, which-ever occur first (Up to 17 months) |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Progression Free Survival (PFS) |
Time Frame: | From the start of study treatment until disease progression/recurrence or death from any cause, whichever occurs first (Up to 17 months) |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Percentage of Participants with PFS at Month 6, 12 and 18 |
Time Frame: | Month 6, 12 and 18 |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Overall Survival (OS) |
Time Frame: | From the start of study treatment until death from any cause, whichever occurs first (Up to 17 months) |
Safety Issue: | |
Description: | |
Measure: | Part A and B: OS Rate at Month 12 and 18 |
Time Frame: | Month 12 and 18 |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Area Under the Curve (AUC) of Debio 1143 and Debio 1143-MET1 |
Time Frame: | Part A: Day 1, 3, 8, 15, 17, 22 Cycle 1 (each cycle is 28 days); Day 1, 3, 15, 17 Cycle 3; Day 1 Cycle 6. Part B: Day 1, 8, 15, 22 Cycle 1; Day 1, 15, Cycle 3; Day 1 Cycle 6; End of Treatment (Up to 17 months) |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Maximum Observed Concentration (Cmax) of Debio 1143 and Debio 1143-MET1 |
Time Frame: | Part A: Day 1, 3, 8, 15, 17, 22 Cycle 1 (each cycle is 28 days); Day 1, 3, 15, 17 Cycle 3; Day 1 Cycle 6. Part B: Day 1, 8, 15, 22 Cycle 1; Day 1, 15, Cycle 3; Day 1 Cycle 6; End of Treatment (Up to 17 months) |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Trough Concentration (Cmin) of Debio 1143 and Debio 1143-MET1 |
Time Frame: | Part A: Day 1, 3, 8, 15, 17, 22 Cycle 1 (each cycle is 28 days); Day 1, 3, 15, 17 Cycle 3; Day 1 Cycle 6. Part B: Day 1, 8, 15, 22 Cycle 1; Day 1, 15, Cycle 3; Day 1 Cycle 6; End of Treatment (Up to 17 months) |
Safety Issue: | |
Description: | |
Measure: | Part A and B: Serum Concentration of Nivolumab |
Time Frame: | Part A: Day 1, 3, 8, 15, 17, 22 Cycle 1 (each cycle is 28 days); Day 1, 3, 15, 17 Cycle 3; Day 1 Cycle 6. Part B: Day 1, 8, 15, 22 Cycle 1; Day 1, 15, Cycle 3; Day 1 Cycle 6; End of Treatment (Up to 17 months) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Debiopharm International SA |
Last Updated
August 26, 2021