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

NCT03270176 | Completed Phase 1

• 2 other identifiers: Debio 1143-NSCLC-1052018-000494-71
• Study Type: interventional
• Target: 54
• Locations: 3 countries
• Sites: 9

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

Outcome Measures

Primary Outcomes (2)

• Part A: Maximum Tolerated Dose (MTD)

  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.

  Baseline up to Cycle 1 (4 Weeks)

• Part B: Objective Response Rate (ORR)

  Objective response is defined as any partial response (PR) or complete response (CR) recorded from the start of study treatment until disease progression/recurrence is documented, a new systemic therapy is started or analysis cut-off, whichever occurs first. It is assessed by using Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1. RECIST v1.1 criteria- CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to \<10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

  From first occurrence of objective response until disease progression or death from any cause or switch to a new systemic therapy or end of study (Up to 2 years)

Secondary Outcomes (9)

• Part A and B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Baseline up to 90 days after the last dose of study drug (up to 2.5 years)

• Part A and B: Change in Tumor Size

  Day 1 of cycle 3 up to 6 months; Day 1 of cycle 9, 12, 15, 18, 21, 24, 26 or until disease progression/EOT (up to 2 years)

• Part A and B: Objective Response Rate

  At the end of Cycle 6 (168 days)

• Part A and B: Best Overall Response (BOR)

  Day 1 of cycle 3 up to 6 months; Day 1 of cycle 9, 12, 15, 18, 21, 24, 26 or until disease progression/EOT (up to 2 years)

• Part A and B: Duration of Response

  Baseline up to Cycle 26 (2 years) or until disease progression/EOT

Study Arms (1)

Debio 1143 and Avelumab

EXPERIMENTAL

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).

Drug: Debio 1143; Drug: Avelumab

Interventions

Debio 1143 DRUG

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

Debio 1143 and Avelumab

Avelumab DRUG

Avelumab 10 mg/kg intravenous infusion every 2 weeks.

Debio 1143 and Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (9)

Cross Cancer Center Dept Medicine

Edmonton, Alberta, T6G 1Z2, Canada

Location

British Columbia Cancer Agency

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

The Ottawa Hospital Cancer Centre (TOHCC)

Ottawa, Ontario, K1H 8L6, Canada

Location

Instytut Medyczny Santa Familia Sp. z o. o.

Lodz, 90-320, Poland

Location

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

Poznan, 60-693, Poland

Location

Wojewódzki Szpital Zespolony im. Ludwika Rydygiera

Torun, 87-100, Poland

Location

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

Cluj-Napoca, 400015, Romania

Location

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

Craiova, 200347, Romania

Location

Related Publications (1)

• 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.

  PMID: 40351326 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

N-benzhydryl-5-(2-(methylamino)propanamido)-3-(3-methylbutanoyl)-6-oxodecahydropyrrolo(1,2-a)(1,5)diazocine-8-carboxamide; avelumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: September 1, 2017
• Study Start: October 10, 2017
• Primary Completion: March 22, 2022
• Study Completion: March 22, 2022
• Last Updated: June 1, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

RO (2); CA (4); PL (3)