Protocol Summary

Protocol No.: OCR23042

Sponsor Protocol No.: SMARTPLUS-106; Debio 1143-106

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

Principal Investigator: Jones, Dennie

Objective: 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).

Phase: Phase II

Age Group: Adult

Age: 18 Years - N/A

Gender: All

Scope: National

Treatment:

Experimental: Debio 1143 + Nivolumab
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.

Detailed Eligibility:

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

Applicable Conditions:

  • Gynecologic Cancer
  • Head & Neck Cancer
  • Lung Cancer
  • Participation Institution:

  • No UF Health MRN : Marlene Sarmiento
  • UF Gainesville : Marlene Sarmiento
  • Contact:
    Marlene Sarmiento
    Phone: +1 352-265-0680 ext. 50704
    Email: msarmien@ufl.edu

    More Information: View study listing on ClinicialTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT04122625