Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143 (SMARTPLUS-106)

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: NCT04122625
Recruitment Status : Recruiting
First Posted : October 10, 2019
Last Update Posted : January 2, 2020
Sponsor:
Information provided by (Responsible Party):
Debiopharm International SA

Brief Summary:

Part A (dose-optimization)- to determine the recommended phase 2 dose (RP2D) taking into account dose-limiting toxicity (DLT/s) in Cycle 1, overall safety/tolerability and pharmacokinetic (PK), by optimizing doses of Debio 1143 when combined with the standard dose of nivolumab, as well as treatment compliance in participants with advanced solid malignancies who failed prior systemic standard treatments.

Part B (basket trial)- to evaluate the preliminary anti-tumor activity of Debio 1143 at the RP2D in combination with nivolumab at the standard dose, overall and in each participant cohort (Cohort 1: small cell lung cancer [SCLC]; Cohort 2: squamous cell carcinoma of the head and neck [SCCHN]; Cohort 3: gastrointestinal (GI) cancers with known microsatellite instability-high/mismatch repair deficiency (MSI-H/MMRd) or other deoxyribonucleic acid (DNA) damage repair (DDR) abnormalities, including homologous recombination deficiency (HRD); Cohort 4: platinum-resistant epithelial ovarian cancer [EOC], endometrial cancer, primary peritoneal cancer (PPC) or cervical cancer, with known MSIH/MMRd, hereditary/somatic mutations of the breast cancer 1 (BRCA1) and BRCA2 genes or other DNA DDR abnormalities (incl. HRD).


Condition or disease Intervention/treatment Phase
Solid Tumor Drug: Debio 1143 Drug: Nivolumab Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Dose-optimization, Exploratory Phase Ib/II Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143, When Given in Combination With the Anti-PD-1 Antibody Nivolumab in Patients With Specific Solid Tumors Who Have Progressed During or Immediately After Anti-PD-1/PD-L1 Treatment
Actual Study Start Date : April 8, 2019
Estimated Primary Completion Date : January 20, 2023
Estimated Study Completion Date : January 20, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Debio 1143 + Nivolumab
Part A: Participants will receive Debio 1143 at a starting dose of 150 milligrams (mg) orally once daily on Days 1-10 and Days 15-24 every 4 weeks (q4w) along with nivolumab at a flat dose of 240 mg intravenously (IV) on Days 1 and 15 of a 28-day cycle, participants may be switched to 480 mg IV on Day 1 q4w, exclusively upon investigator request with the sponsor agreement. Part B: Participants will receive Debio 1143 at RP2D established in Part A in combination with nivolumab as per standard care.
Drug: Debio 1143
Debio 1143 will be administered capsule orally once daily for 10 consecutive days every 2 weeks and Days 15-24 q4w. The dose of Debio 150 mg can be escalated to 200 in Part A and it is to be decided in Part B.

Drug: Nivolumab
Nivolumab will be administered as 240 mg IV infusion on Days 1 and 15 of a 28-day cycle.




Primary Outcome Measures :
  1. Part A: Recommended Phase 2 Dose (RP2D) of Debio1143 [ Time Frame: Up to 28 days (Cycle 1) ]
  2. Part B: Confirmed Objective Response Rate (ORR) [ Time Frame: From first occurrence of objective response until disease progression or death from any cause or end of study (Up to 17 months) ]

Secondary Outcome Measures :
  1. Part A and B: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Laboratory Abnormalities [ Time Frame: Up to 17 months ]
  2. Part A and B: Number of Participants with Change in Weight [ Time Frame: Up to 17 months ]
  3. Part A and B: Number of Participants with Change in Vital Signs [ Time Frame: Up to 17 months ]
  4. Part A and B: Number of Participants with Change in Temperature [ Time Frame: Up to 17 months ]
  5. Part A and B: Number of Participants with Change in Electrocardiogram (ECG) [ Time Frame: Up to 17 months ]
  6. Part A and B: Number of Participants with Change in Eastern Cooperative Oncology Group performance status (ECOG-PS) [ Time Frame: Up to 17 months ]
  7. Part A and B: Number of Participants Leading to Treatment Discontinuations and Treatment Modifications due to AEs and Laboratory Abnormalities [ Time Frame: Up to 17 months ]
  8. Part A: Confirmed Objective Response Rate (ORR) [ Time Frame: From first occurrence of objective response until disease progression or death from any cause or end of study (Up to 17 months) ]
  9. Part A and B: Unconfirmed Objective Response Rate (ORR) [ Time Frame: From first occurrence of objective response until disease progression or death from any cause or end of study (Up to 17 months) ]
  10. Part A and B: Disease Control Rate (DCR) [ Time Frame: From the start of study treatment until disease progression/recurrence or analysis cut-off, whichever occurs first (Up to 17 months) ]
  11. Part A and B: Time to Response (TTR) [ Time Frame: From the date of first dose to the date of the first documented evidence of response (Up to 17 months) ]
  12. Part A and B: Duration of Response (DOR) [ Time Frame: From the time of documentation of response to disease progression or analysis cut-off date, which-ever occur first (Up to 17 months) ]
  13. Part A and B: Progression Free Survival (PFS) [ Time Frame: From the start of study treatment until disease progression/recurrence or death from any cause, whichever occurs first (Up to 17 months) ]
  14. Part A and B: Percentage of Participants with PFS at Month 6, 12 and 18 [ Time Frame: Month 6, 12 and 18 ]
  15. Part A and B: Overall Survival (OS) [ Time Frame: From the start of study treatment until death from any cause, whichever occurs first (Up to 17 months) ]
  16. Part A and B: OS Rate at Month 12 and 18 [ Time Frame: Month 12 and 18 ]
  17. Part A and B: Area Under the Curve (AUC) of Debio 1143 and Debio 1143-MET1 [ Time Frame: Part A: Day 1, 3, 8, 15, 17, 22 Cycle 1 (each cycle is 28 days); Day 1, 3, 15, 17 Cycle 3; Day 1 Cycle 6. Part B: Day 1, 8, 15, 22 Cycle 1; Day 1, 15, Cycle 3; Day 1 Cycle 6; End of Treatment (Up to 17 months) ]
  18. Part A and B: Maximum Observed Concentration (Cmax) of Debio 1143 and Debio 1143-MET1 [ Time Frame: Part A: Day 1, 3, 8, 15, 17, 22 Cycle 1 (each cycle is 28 days); Day 1, 3, 15, 17 Cycle 3; Day 1 Cycle 6. Part B: Day 1, 8, 15, 22 Cycle 1; Day 1, 15, Cycle 3; Day 1 Cycle 6; End of Treatment (Up to 17 months) ]
  19. Part A and B: Trough Concentration (Cmin) of Debio 1143 and Debio 1143-MET1 [ Time Frame: Part A: Day 1, 3, 8, 15, 17, 22 Cycle 1 (each cycle is 28 days); Day 1, 3, 15, 17 Cycle 3; Day 1 Cycle 6. Part B: Day 1, 8, 15, 22 Cycle 1; Day 1, 15, Cycle 3; Day 1 Cycle 6; End of Treatment (Up to 17 months) ]
  20. Part A and B: Serum Concentration of Nivolumab [ Time Frame: Part A: Day 1, 3, 8, 15, 17, 22 Cycle 1 (each cycle is 28 days); Day 1, 3, 15, 17 Cycle 3; Day 1 Cycle 6. Part B: Day 1, 8, 15, 22 Cycle 1; Day 1, 15, Cycle 3; Day 1 Cycle 6; End of Treatment (Up to 17 months) ]


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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have received at least one prior line of standard systemic chemotherapy in the advanced/unresectable cancer setting (standard adjuvant/neoadjuvant treatment is acceptable if relapse occurred within six months of treatment end)
  • Have progressed or relapsed during or after a prior anti-programmed cell death-1 (PD-1)/ programmed cell death-ligand 1 (PD-L1)-based treatment, given either as a single agent or in combination with standard/approved chemotherapy, tyrosine kinase inhibitors (TKIs), radiotherapy (RT) or other monoclonal antibodies (mAbs) that are not known to modulate/inhibit immune checkpoints (CPIs)
  • Measurable disease (Part B only) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or Gynecologic Cancer Intergroup (GCIG) criteria in Cohort #4 (if applicable) and documented PD during or after prior PD-1/PD-L1 based therapy

Exclusion Criteria:

  • Thoracic or head and neck radiation >30 gray (Gy) within the 3 months prior to Cycle 1 Day 1 (C1D1)
  • Have received, in total, more than 3 (i.e. Cohorts 1&2) or 4 (i.e. Cohorts 3&4) lines of prior systemic treatments (including adjuvant or neoadjuvant regimens if relapse within six months prior to C1D1)
  • Liver cirrhosis Child-Pugh score B or C

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): NCT04122625


Contacts
Layout table for location contacts
Contact: Debiopharm International S.A +41 21 321 01 11 clinicaltrials@debiopharm.com

Locations
Layout table for location information
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32611
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612-9497
United States, Michigan
University of Michigan Comprehensive Cancer Center Not yet recruiting
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Montefiore Medical Center PRIME Recruiting
Bronx, New York, United States, 10461
United States, Ohio
UC Health, LLC. Recruiting
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
St. Luke's University Health Network Recruiting
Bethlehem, Pennsylvania, United States, 18015
United States, Washington
Georgetown University - Lombardi Comprehensive Cancer Center Recruiting
Northwest, Washington, United States, 20007
France
Centre Leon Berard Recruiting
Lyon, France, 69008
Institut Universitaire du Cancer de Toulouse Oncopole Recruiting
Toulouse, France, 31100
Institut Gustave Roussy Recruiting
Villejuif, France, 94800
Spain
Hospital Vall d'Hebron Recruiting
Barcelona, Spain, 08035
START Madrid, Fundacion Jimenez Diaz Recruiting
Madrid, Spain, 28040
START Madrid, H.U. Sanchinarro Recruiting
Madrid, Spain, 28050
Sponsors and Collaborators
Debiopharm International SA

Layout table for additonal information
Responsible Party: Debiopharm International SA
ClinicalTrials.gov Identifier: NCT04122625    
Other Study ID Numbers: Debio 1143-106
2018-003546-16 ( EudraCT Number )
First Posted: October 10, 2019    Key Record Dates
Last Update Posted: January 2, 2020
Last Verified: December 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents