Clinical Trials /

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

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: Debio 1143-NSCLC-105
  • NCT ID: NCT03270176

Conditions

  • Carcinoma, Non-Small-Cell Lung
  • Neoplasms

Interventions

DrugSynonymsArms
Debio 1143Debio 1143 and Avelumab
AvelumabDebio 1143 and Avelumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Debio 1143 and AvelumabExperimentalPart 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 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) established in Part A along with avelumab IV infusion at a RP2D dose established in Part A up to years unless disease progression or unacceptable toxicity occurs, as judged by investigators.
  • Debio 1143
  • Avelumab

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 anaphylactic
             lymphoma kinase (ALK) translocation/rearrangement (testing required if status is
             unknown).

          -  More than one line of treatment for metastatic or recurrent NSCLC.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: Maximum Tolerated Dose (MTD)
Time Frame:Baseline up to Cycle 1 (4 Weeks)
Safety Issue:
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.

Secondary Outcome Measures

Measure:Part A and B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:Baseline up to 30 days after the last dose of study drug (up to 2.3 years)
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03.
Measure:Part A and B: Change in Tumor Size
Time Frame:Day 1 of cycle 3 up to 6 months; Day 1 of cycle 9, 12, 15, 18, 21, 24 or until disease progression/EOT (up to 2 years)
Safety Issue:
Description:Change in tumor size is the maximum reduction or, in case of no reduction, the minimum increase in tumor size from the start of study treatment until disease progression/recurrence, the start of a new systemic therapy or analysis cut-off, whichever occurs first.
Measure:Part A and B: Objective Response Rate
Time Frame:At the end of Cycle 6 (168 days)
Safety Issue:
Description:Objective response is defined as any PR or 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 RECIST criteria. CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.
Measure:Part A and B: Best Overall Response (BOR)
Time Frame:Day 1 of cycle 3 up to 6 months; Day 1 of cycle 9, 12, 15, 18, 21, 24 or until disease progression/EOT (up to 2 years)
Safety Issue:
Description:Best overall response (BOR) is defined as the best response (CR, PR, stable disease or disease progression) 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 RECIST criteria version 1.1. 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. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Stable Disease: Neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for disease progression, taking as reference the smallest sum diameter while on study.
Measure:Part A and B: Duration of Response
Time Frame:Baseline up to 2 years or until disease progression/EOT
Safety Issue:
Description:Duration of response is the time from documentation of tumor response to disease progression was observed in participants with CR or PR. 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. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Measure:Part A and B: Disease Control Rate
Time Frame:Day 1 of cycle 3 up to 6 months; Day 1 of cycle 9, 12, 15, 18, 21, 24 or until disease progression/EOT (up to 2 years)
Safety Issue:
Description:Disease control is derived as CR, PR or stable disease lasting at least 12 weeks reported during the study. RECIST v1.1 criteria- CR: Disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.
Measure:Part A and B: Progression Free Survival (PFS)
Time Frame:Up to 6 months, 1 and 2 years of treatment initiation
Safety Issue:
Description:PFS duration is defined as the time elapsed between treatment initiation and tumor progression or death from any cause, whichever occurs first. RECIST v1.1 criteria- CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Measure:Part A and B: Overall Survival (OS)
Time Frame:Up to 6 months, 1 and 2 years of treatment initiation
Safety Issue:
Description:OS is defined as the time elapsed between treatment initiation and death from any cause.
Measure:Part A and B: Assessment of Pharmacokinetic Parameters
Time Frame:up to Cycle 25 (700 days)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Debiopharm International SA

Last Updated