SMARTPLUS-106: Debio 1143 a SMAC Mimetic in Combination with Nivolumab in Patients Failing Prior PD-1/PD-L1 Treatment: A Basket Trial

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).

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