A Phase 1a/1b Open-Label, Multicenter, Dose Escalation, and Dose Expansion Trial to Evaluate the Safety and Activity of TEV-56278, as a Monotherapy and in Combination With Pembrolizumab in Participants With Selected Locally Advanced or Metastatic Solid Tumors
Summary
The primary objectives of this trial are to: * Characterize the safety and tolerability of TEV-56278 * Determine the Recommended Phase 2 Dose (RP2D) * Evaluate antitumor activity of TEV-56278 (Part 2 only) * Determine the safety and tolerability of TEV-56278 in combination with pembrolizumab * Determine a RP2D of TEV-56278 in combination with pembrolizumab The secondary objectives of this trial are to: * Characterize the serum pharmacokinetics of TEV-56278 * Evaluate the antitumor activity of TEV-56278 * Determine the safety and tolerability of TEV-56278 * Evaluate other measures of antitumor activity of TEV-56278 * Evaluate anti-tumor activity Participants will be treated up to 12 months with a follow-up period of up to 12 months after last infusion. The total duration of the trial will be up to 25 months for individual participants. Participants who exhibit a favorable benefit risk profile at the end of the 12 month trial treatment period may be offered an opportunity for an extended treatment period in which they can be treated for a maximum of 12 additional months (up to 26 additional cycles of TEV-56278).
Arms & interventions
- DrugTEV-56278
Administered intravenously
- DrugPembrolizumab
Administered intravenously
Outcome measures
Primary
Incidence of AEs with CTCAE Grade≥3 in the escalation phase
CTCAE: Common Terminology Criteria for Adverse Events
Time frame: Up to 15 months after 1st infusion in the escalation phase
Incidence of SAEs in the escalation phase
Time frame: Up to 15 months after 1st infusion in the escalation phase
Incidence of AEs meeting protocol-defined DLT criteria in the escalation phase
DLT: dose-limiting toxicity
Time frame: Up to 28 days after 1st infusion in the escalation phase
Incidence of dose modifications due to AEs in the escalation phase
Time frame: Up to 12 months after 1st infusion in the escalation phase
Incidence of AEs leading to discontinuation in the escalation phase
Time frame: Up to 12 months after 1st infusion in the escalation phase
Recommended Phase 2 dose as monotherapy
Time frame: Up to 24 months after 1st infusion
Objective Response Rate (ORR) based on RECIST (v 1.1) criteria in the expansion phase
RECIST: Response Evaluation Criteria in Solid Tumors.
Time frame: Up to 24 months after the 1st dose in the expansion phase
Duration of Response (DOR) in the expansion phase
Time frame: Up to 24 months after the 1st dose in the expansion phase
Recommended Phase 2 dose in combination with Pembrolizumab
Time frame: Up to 24 months after 1st dose
Incidence of AEs with CTCAE Grade≥3 in the combination phase
Time frame: Up to 15 months after 1st infusion in the combination phase
Incidence of SAEs in the combination phase
Time frame: Up to 15 months after 1st infusion in the combination phase
Incidence of AEs meeting protocol-defined DLT criteria in the combination phase
Time frame: Up to 28 days after 1st infusion in the combination phase
Incidence of dose modifications due to AEs in the combination phase
Time frame: Up to 12 months after 1st infusion in the combination phase
Incidence of AEs leading to discontinuation in the combination phase
Time frame: Up to 12 months after 1st infusion in the combination phase
Secondary
AUC0-last
Time frame: Predose up to Day 8
Cmax
Time frame: Predose up to Day 8
tmax
Time frame: Predose up to Day 8
Objective Response Rate (ORR) based on RECIST (v1.1) criteria in the escalation phase
Time frame: Up to 24 months after 1st infusion in the escalation phase
Incidence of AEs with CTCAE (v5.0) Grade≥3 in the expansion phase
Time frame: Up to 24 months after 1st infusion in the expansion phase
Incidence of SAEs in the expansion phase
Time frame: Up to 15 months after 1st infusion in the expansion phase
Incidence of dose modifications due to AEs in the expansion phase
Time frame: Up to 12 months after 1st infusion in the expansion phase
Incidence of AEs leading to discontinuation in the expansion phase
Time frame: Up to 12 months after 1st infusion in the expansion phase
Disease Control Rate (DCR) according to RECIST (v1.1) criteria
Time frame: Up to 24 months after 1st infusion
Time to Respond (TTR) according to RECIST (v1.1) criteria
Time frame: Up to 24 months after 1st infusion
Objective Response Rate (ORR) based on RECIST criteria in the combination phase
Time frame: Up to 24 months after 1st infusion in the combination phase
Eligibility criteria
Study locations (11)
Teva Investigational Site 12017
Los Angeles, California, 90025
Teva Investigational Site 12021
Lake Mary, Florida, 32746
Teva Investigational Site 12016
Chicago, Illinois, 60611
Teva Investigational Site 12015
Detroit, Michigan, 48201
Teva Investigational Site 12014
Huntersville, North Carolina, 28078
Teva Investigational Site 12023
Cincinnati, Ohio, 45219
Teva Investigational Site 12058
Pittsburgh, Pennsylvania, 15232
Teva Investigational Site 12019
Nashville, Tennessee, 37203
Teva Investigational Site 12024
Nashville, Tennessee, 37232
Teva Investigational Site 12018
Fairfax, Virginia, 22031
Teva Investigational Site 12025
Milwaukee, Wisconsin, 53226