The purpose of this study is to test the safety and tolerability of HFB200603 as a single agent and in combination with tislelizumab in patients with advanced cancers. There are two parts in this study. During the escalation part, groups of participants will receive increasing doses of HFB200603 as a monotherapy or in combination with tislelizumab until a safe and tolerable dose of HFB200603 as a single agent or combination therapy is determined. During the expansion part, participants will take the doses of HFB200603 as a monotherapy (optional arm) or in combination with tislelizumab that were determined from the escalation part of the study and will be assigned to a group based on the type of cancer the participants have.
This is a Phase 1a/b, first in human, open-label, dose escalation and expansion study in adults with advanced cancers. The study will comprise of 1. A Screening Period of up to 28 days 2. A Treatment Period during which participants will receive the study drug on the first day of each cycle where each cycle is 21 days. Number of cycles depends on how the disease responds to the study drug 3. A Follow-up Period which involves 2 visits
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
83
Participants will be administered HFB200603 as described in the experimental arm.
Participants will be administered tislelizumab as described in the experimental arm.
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
New Experimental Therapeutics of Virginia - NEXT Oncology
Fairfax, Virginia, United States
Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
Naples, Italy
UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
Rome, Italy
Centro Ricerche Cliniche di Verona s.r.l.
Verona, Italy
Clinica Universidad de Navarra - Madrid
Madrid, Spain
South Texas Accelerated Research Therapeutics (START) Madrid - Hospital Fundacion Jimenez Diaz
Madrid, Spain
South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC
Madrid, Spain
Clinica Universidad de Navarra - Pamplona
Pamplona, Spain
...and 1 more locations
Number of participants with adverse events (AEs) meeting protocol-defined Dose-Limiting Toxicity (DLT) criteria during Dose Escalation
Severity of adverse events will be based on common terminology criteria for adverse events (CTCAE) version 5.0
Time frame: The first cycle of treatment (Day 1 up to Day 21)
Number of participants with AEs
Severity of AEs will be assessed based on CTCAE version 5.0 (except for cytokine release syndrome which will be assessed by American Society for Transplantation and Cellular Therapy grading)
Time frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years
Number of participants with changes in laboratory values
Time frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years
Number of participants with changes in vital signs
Time frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years
Number of participants with changes in electrocardiogram (ECG)
Time frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years
Number of participants with changes in tolerability (dose interruptions and dose intensity)
Time frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years
To determine a Recommended Phase 2 Dose (RP2D) during Dose Expansion
Time frame: Cycle 1 Day 1 to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years
Objective Response Rate (ORR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-RECIST (iRECIST)
Time frame: Baseline to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years
Disease Control Rate (DCR) as determined by RECIST 1.1 and iRECIST
Time frame: Baseline to 90 days after the last dose of study drug(s) (each cycle is 21 days), assessed up to 3 years
Duration of Response (DOR) as determined by RECIST 1.1 and iRECIST
Time frame: Start of first response to first date of disease progression, clinical progression or death, whichever occurs first, assessed up to 3 years
Progression Free Survival (PFS) as determined by RECIST 1.1 and iRECIST
Time frame: Baseline to disease progression or death, whichever occurs first, assessed up to 3 years
Minimum serum concentration (Cmin)
Time frame: Cycle 1 Day 1 to day of the last dose of study drug(s) (each cycle is 21 days), through study completion, an average of 3 year
Maximum serum concentration (Cmax)
Time frame: Cycle 1 Day 1 to day of the last dose of study drug(s) (each cycle is 21 days), through study completion, an average of 3 year
Area under the concentration versus time curve (AUC)
Time frame: Cycle 1 Day 1 to day of the last dose of study drug(s) (each cycle is 21 days), through study completion, an average of 3 year
Terminal half-life (T1/2)
Time frame: Cycle 1 Day 1 to day of the last dose of study drug(s) (each cycle is 21 days), through study completion, an average of 3 year
Serum concentration for measurement of anti-HFB200603 antibodies
Time frame: Cycle 1 Day 1 to day of the last dose of study drug(s) (each cycle is 21 days), through study completion, an average of 3 year
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