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Clinical Trial 20123

Cancer Type: Multiple
Study Type: Treatment
NCT#: NCT04122625

Phase: Phase I/II
Prinicipal Investigator:

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Overview

Study 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

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).

Objective

Primary Objectives Part A: The primary objective of the dose-optimization part of the study is to determine the RP2D taking into account DLT/s in Cycle 1, overall safety/tolerability and PK, by optimizing doses of Debio 1143 when combined with the standard dose of nivolumab, as well as treatment compliance in patients with advanced solid malignancies who failed prior systemic standard treatments. Part B: The primary objective of the basket trial is 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 patient cohort. Secondary Objectives: Part A: For the dose-optimization part, secondary objectives are to assess the: 1. PK disposition of Debio 1143 (including its metabolite Debio 1143-MET1) and nivolumab when administered in combination. 2. Anti-tumor activity of Debio 1143 in combination with nivolumab in patients with advanced solid malignancies. Part B: For the basket trial, secondary objectives are to assess the: 1. Safety and tolerability of the RP2D of Debio 1143 when given in combination with nivolumab in patients with advanced solid malignancies. 2. PK disposition of Debio 1143 (and its metabolite Debio 1143-MET1) and nivolumab when administered in combination.

Treatments

Therapies

Medications

BMS-936558 (Nivolumab); Debio 1143 (); Nivolumab ()

Inclusion 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

    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

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