Clinical trial NCT03270176: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Neoplasms
Lead sponsor: Debiopharm International SA
Sponsor class: INDUSTRY
First posted: 2017-09-01
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Part A: Maximum Tolerated Dose (MTD)
timeFrame: Baseline up to Cycle 1 (4 Weeks)
measure: Part B: Objective Response Rate (ORR)
timeFrame: 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:
measure: Part A and B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to 90 days after the last dose of study drug (up to 2.5 years)
measure: Part A and B: Change in Tumor Size
timeFrame: 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)
measure: Part A and B: Objective Response Rate
timeFrame: At the end of Cycle 6 (168 days)
measure: Part A and B: Best Overall Response (BOR)
timeFrame: 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)
measure: Part A and B: Duration of Response
timeFrame: Baseline up to Cycle 26 (2 years) or until disease progression/EOT
measure: Part A and B: Disease Control Rate
timeFrame: 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)
measure: Part A and B: Progression Free Survival (PFS)
timeFrame: Up to 6 months, 1 and 2 years of treatment initiation
measure: Part A and B: Overall Survival (OS)
timeFrame: Up to 6 months, 1 and 2 years of treatment initiation
measure: Part A and B: Assessment of Pharmacokinetic Parameters
timeFrame: Up to Cycle 25 (700 days)
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Cross Cancer Center Dept Medicine
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre (TOHCC)
state: Ontario
city: Poznań
country: Poland
facility: Med-Polonia Sp. z o.o., Ulica Obornicka
city: Toruń
country: Poland
facility: Wojewódzki Szpital Zespolony im. Ludwika Rydygiera
city: Łódź
country: Poland
facility: Instytut Medyczny Santa Familia Sp. z o. o.
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic "Prof. Dr. Ion Chiricuţă" Cluj Napoca
city: Craiova
country: Romania
facility: Centrul de Oncologie, S.C. Centrul de Oncologie Sf. Nectarie S.R.L, Oncologie Medicala
Study officials:
References: