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

NCT ID: NCT03270176

Last Updated: 2022-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-10
• Study Completion Date: 2022-03-22

Brief Summary

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

Carcinoma, Non-Small-Cell Lung; Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Debio 1143 and Avelumab

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).

Group Type: EXPERIMENTAL

Debio 1143

Intervention Type: DRUG

Debio 1143 100 to 250 mg, capsule orally for 10 days every 2 weeks.

Avelumab

Intervention Type: DRUG

Avelumab 10 mg/kg intravenous infusion every 2 weeks.

Interventions

Debio 1143

Debio 1143 100 to 250 mg, capsule orally for 10 days every 2 weeks.

Intervention Type: DRUG

Avelumab

Avelumab 10 mg/kg intravenous infusion every 2 weeks.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Debiopharm International SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cross Cancer Center Dept Medicine

Edmonton, Alberta, Canada

British Columbia Cancer Agency

Vancouver, British Columbia, Canada

Juravinski Cancer Centre

Hamilton, Ontario, Canada

The Ottawa Hospital Cancer Centre (TOHCC)

Ottawa, Ontario, Canada

Instytut Medyczny Santa Familia Sp. z o. o.

Lodz, , Poland

Med-Polonia Sp. z o.o., Ulica Obornicka

Poznan, , Poland

Wojewódzki Szpital Zespolony im. Ludwika Rydygiera

Torun, , Poland

Institutul Oncologic "Prof. Dr. Ion Chiricuţă" Cluj Napoca

Cluj-Napoca, , Romania

Centrul de Oncologie, S.C. Centrul de Oncologie Sf. Nectarie S.R.L, Oncologie Medicala

Craiova, , Romania

Countries

Canada; Poland; Romania

References

Goss 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.

Reference Type: DERIVED

PMID: 40351326 (View on PubMed)

Other Identifiers

2018-000494-71

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Debio 1143-NSCLC-105

Identifier Type: -

Identifier Source: org_study_id