ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03270176
Recruitment Status : Recruiting
First Posted : September 1, 2017
Last Update Posted : October 24, 2018
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA

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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Neoplasms Drug: Debio 1143 Drug: Avelumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 10, 2017
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: 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 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.

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

Drug: Avelumab
Avelumab 10 mg/kg intravenous infusion every 2 weeks.




Primary Outcome Measures :
  1. Part A: Maximum Tolerated Dose (MTD) [ Time Frame: Baseline up to Cycle 1 (4 Weeks) ]
    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.

  2. Part B: Objective Response Rate (ORR) [ Time Frame: 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) ]
    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.


Secondary Outcome Measures :
  1. 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) ]
    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.

  2. 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) ]
    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.

  3. Part A and B: Objective Response Rate [ Time Frame: At the end of Cycle 6 (168 days) ]
    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.

  4. 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) ]
    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.

  5. Part A and B: Duration of Response [ Time Frame: Baseline up to 2 years or until disease progression/EOT ]
    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).

  6. 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) ]
    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.

  7. Part A and B: Progression Free Survival (PFS) [ Time Frame: Up to 6 months, 1 and 2 years of treatment initiation ]
    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).

  8. Part A and B: Overall Survival (OS) [ Time Frame: Up to 6 months, 1 and 2 years of treatment initiation ]
    OS is defined as the time elapsed between treatment initiation and death from any cause.

  9. Part A and B: Assessment of Pharmacokinetic Parameters [ Time Frame: up to Cycle 25 (700 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03270176


Contacts
Contact: Debiopharm International S.A +41 21 321 01 11 clinicaltrials@debiopharm.com

Locations
Canada, Alberta
Cross Cancer Center Dept Medicine Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Dr. Quincy Chu         
Canada, British Columbia
British Columbia Cancer Agency Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Dr. Daniel Renouf         
Canada, Ontario
Juravinski Cancer Centre Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Dr. Rosalyn Juergens         
The Ottawa Hospital Cancer Centre (TOHCC) Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Dr. Glennwood Goss         
Sponsors and Collaborators
Debiopharm International SA

Responsible Party: Debiopharm International SA
ClinicalTrials.gov Identifier: NCT03270176     History of Changes
Other Study ID Numbers: Debio 1143-NSCLC-105
First Posted: September 1, 2017    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs