Clinical trial · Interventional
A Dose-Finding Study of the Second Mitochondrial Activator of Caspases (SMAC) Mimetic Debio 1143 When Given in Combination With Avelumab to Participants With Advanced Solid Malignancies and to Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Platinum-Based Therapy
A Phase-Ib Dose-Finding Study of the SMAC Mimetic Debio 1143 When Given in Combination With the Anti-PD-L1 Antibody Avelumab to Patients With Advanced Solid Malignancies and, in an Expansion Cohort, to Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Platinum-Based Therapy
NCT03270176CI-TRIAL-00058854completedPhase 1ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The study is primarily designed to assess the safety and tolerability of escalating oral doses of Debio 1143 and preliminary anti-tumour activity when combined with the standard dose of avelumab in participants with advanced solid malignancies.
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Carcinoma, Non-Small-Cell Lung | Lung Non-Small Cell Carcinoma | ALIAS | 0.90 |
| Neoplasms | Neoplasm | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Avelumab | Drug | Avelumab | ALIAS |
| Debio 1143 | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Debio 1143 and Avelumab
- description
- Part A: Participants will receive Debio 1143 100 to 250 milligram (mg) capsule orally at an escalating dose levels for 10 days every 2 weeks along with avelumab 10 milligrams per kilogram (mg/kg) as an intravenous (IV) infusion every 2 weeks. Part B: Participants will receive Debio 1143 capsules orally at a recommended phase 2 dose (RP2D) of 200 mg/day (days 1-10 and 15-24 every 28 days (\[q4w\]) in combination with avelumab IV infusion at the standard dose unless disease progression or unacceptable toxicity occurs, as judged by investigators up to 26 cycles (each cycle is of 28 days).
- interventionNames
- Drug: Debio 1143
- Drug: Avelumab
Primary outcomes (2)
- measure
- Part A: Maximum Tolerated Dose (MTD)
- timeFrame
- Baseline up to Cycle 1 (4 Weeks)
- description
- MTD:dose with estimated probability of dose limited toxicity(DLT) below 30%.DLT:any of following adverse events(AEs) during 1st treatment cycle if deemed related to treatment:grade (gr) 3/4 febrile neutropenia/any gr 4 neutropenia of \>5 days duration;gr 4 thrombocytopenia\[\<25000 per cubic millimetre(/mm\^3)\]/gr 3(\<50000/mm\^3),associated with medically concerning bleeding;gr ≥3 non-hematologic laboratory value;non-hematologic toxicity of gr 3/4,gr ≥2 uveitis/eye pain that does neither respond to topical therapy nor abate to gr 1within the avelumab re-treatment period/that required systemic treatment;gr ≥2 pneumonitis/interstitial lung disease that not resolve with dose delay and systemic steroids;toxicity related to study drug that requires dosing delay of \>2weeks,dose reduction,premature discontinuation of any of two;other drug related AE in the opinion of investigator is of potential clinical significance so that further dose-escalation would expose participants to unacceptable risk.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: Part A • With advanced solid malignancies who are not eligible for standard therapy or for whom standard therapy has failed Part B • With histologically or cytologically confirmed NSCLC of stage IIIB or IV (per 7th International Association for the Study of Lung Cancer classification) that has progressed after one line of platinum containing doublet chemotherapy Part A and B * Willingness and feasibility to provide a tumor biopsy sample both at screening and during treatment (If archived tumor material not older than 1 year is available, then the screening biopsy will not be performed). * Participants with prior radiation therapy must have measurable disease in non-irradiated sites or documented evidence of progression within the radiation field. * With known central nervous system (CNS) must have completed primary brain therapy (such as whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection) and must have remained clinically stable, asymptomatic, and without steroid treatment for at least 21 days. Exclusion Criteria: * Not recovered (i.e. toxicity grade \>1) from prior investigational drug and/or anti-cancer therapy (chemo- or palliative radiotherapy). * Symptomatic and/or progressive brain metastasis or carcinomatous meningitis. * Immunosuppressive agents (such as steroids) for any reason should be tapered off before initiation of study treatment (except low-dose prednisone at a total dose of up to 10 mg/day). Part B only * Tumor activating epidermal growth factor receptor (EGFR) mutation(s) or anaplastic lymphoma kinase (ALK)/ROS1 translocation/rearrangement (testing required in non-squamous participants if status is unknown). * More than one prior line of chemotherapy and one line of anti-PD1/PDL1 therapy.
References
Publications (1)
- DERIVEDGoss G, Ciuleanu T, Ramlau R, Renouf DJ, Chu Q, Kalinka E, Sawrycki P, Bramson J, Nelson BH, Crabbe R, LaCasse E, Lo B, Sahlender DA, Crompton P, Brichory F, Piggott L, Schenker M, Juergens R. Xevinapant plus avelumab in advanced solid tumours, with a dose expansion in advanced non-small-cell lung cancer: exploratory biomarker, safety and efficacy analyses from an open-label, nonrandomised phase Ib study. Ther Adv Med Oncol. 2025 May 8;17:17588359251332154. doi: 10.1177/17588359251332154. eCollection 2025. PMID 40351326