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.
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
- SECONDARY ID:
2018-000494-71
- NCT ID:
NCT03270176
Conditions
- Carcinoma, Non-Small-Cell Lung
- Neoplasms
Interventions
Drug | Synonyms | Arms |
---|
Debio 1143 | | Debio 1143 and Avelumab |
Avelumab | | Debio 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
Name | Type | Description | Interventions |
---|
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). | |
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.
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 90 days after the last dose of study drug (up to 2.5 years) |
Safety Issue: | |
Description: | An AE is any untoward medical occurrence in a clinical investigation participant 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, 26 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, 26 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 Cycle 26 (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, 26 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 16 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: | Active, not recruiting |
Lead Sponsor: | Debiopharm International SA |
Last Updated
August 26, 2021