Clinical trial NCT06480552: An Open-label Dose Escalation/Expansion Trial to Evaluate the Safety and Anti-tumor Activity of TEV-56278 Alone or in Combination With Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2024-06-28
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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
* 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.


Eligibility criteria: Inclusion Criteria:

* Have an established histological diagnosis of selected solid tumor and must have received and progressed on established standard therapies or have been intolerant to such therapy or have been considered by the Investigator as ineligible for approved standard therapy
* Have a life expectancy≥12 weeks at the time of the screening
* Women of childbearing potential must agree to use highly effective methods of contraception for the course of the trial through 120 days after the last dose of trial medication
* Males who are sexually active with women of childbearing potential must agree to use condoms and refrain from donating sperm for the course of the trial through 120 days after the last dose of trial medication

NOTE- Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

* Has a history of systemic treatment therapy for cancer (including chemotherapy, immunotherapy, radiotherapy, or other investigational drug) or surgery within 4 weeks prior to baseline
* Is currently receiving or has received hematopoietic colony-stimulating growth factors within 2 weeks before screening or transfusion support 4 weeks prior to screening
* Has a diagnosis of immunodeficiency
* Has active known autoimmune disease.
* Has a history of or known active brain metastases and/or carcinomatous meningitis and/or leptomeningeal metastasis
* Has active or uncontrolled serious infections requiring systemic therapy within 14 days prior to baseline
* Has a history of clinically significant cardiovascular or cerebrovascular disease in previous 6 months prior to screening
* Has evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis
* Has a seizure disorder requiring therapy (such as steroids or antiepileptics)

NOTE- Additional criteria apply, please contact the investigator for more information

Primary outcomes:
measure: Incidence of AEs with CTCAE Grade≥3 in the escalation phase
timeFrame: Up to 15 months after 1st infusion in the escalation phase
measure: Incidence of SAEs in the escalation phase
timeFrame: Up to 15 months after 1st infusion in the escalation phase
measure: Incidence of AEs meeting protocol-defined DLT criteria in the escalation phase
timeFrame: Up to 28 days after 1st infusion in the escalation phase
measure: Incidence of dose modifications due to AEs in the escalation phase
timeFrame: Up to 12 months after 1st infusion in the escalation phase
measure: Incidence of AEs leading to discontinuation in the escalation phase
timeFrame: Up to 12 months after 1st infusion in the escalation phase
measure: Recommended Phase 2 dose as monotherapy
timeFrame: Up to 24 months after 1st infusion
measure: Objective Response Rate (ORR) based on RECIST criteria in the expansion phase
timeFrame: Up to 24 months after the 1st dose in the expansion phase
measure: Duration of Response (DOR) in the expansion phase
timeFrame: Up to 24 months after the 1st dose in the expansion phase
measure: Recommended Phase 2 dose in combination with Pembrolizumab
timeFrame: Up to 24 months after 1st dose
measure: Incidence of AEs with CTCAE Grade≥3 in the combination phase
timeFrame: Up to 15 months after 1st infusion in the combination phase
measure: Incidence of SAEs in the combination phase
timeFrame: Up to 15 months after 1st infusion in the combination phase
measure: Incidence of AEs meeting protocol-defined DLT criteria in the combination phase
timeFrame: Up to 28 days after 1st infusion in the combination phase
measure: Incidence of dose modifications due to AEs in the combination phase
timeFrame: Up to 12 months after 1st infusion in the combination phase
measure: Incidence of AEs leading to discontinuation in the combination phase
timeFrame: Up to 12 months after 1st infusion in the combination phase
Secondary outcomes:
measure: AUC0-last
timeFrame: Predose up to Day 8
measure: Cmax
timeFrame: Predose up to Day 8
measure: tmax
timeFrame: Predose up to Day 8
measure: Objective Response Rate (ORR) based on RECIST criteria in the escalation phase
timeFrame: Up to 24 months after 1st infusion in the escalation phase
measure: Incidence of AEs with CTCAE Grade≥3 in the expansion phase
timeFrame: Up to 24 months after 1st infusion in the expansion phase
measure: Incidence of SAEs in the expansion phase
timeFrame: Up to 15 months after 1st infusion in the expansion phase
measure: Incidence of dose modifications due to AEs in the expansion phase
timeFrame: Up to 12 months after 1st infusion in the expansion phase
measure: Incidence of AEs leading to discontinuation in the expansion phase
timeFrame: Up to 12 months after 1st infusion in the expansion phase
measure: Disease Control Rate (DCR) according to RECIST (v1.1) criteria
timeFrame: Up to 24 months after 1st infusion
measure: Time to Respond (TTR) according to RECIST (v1.1) criteria
timeFrame: Up to 24 months after 1st infusion
measure: Objective Response Rate (ORR) based on RECIST criteria in the combination phase
timeFrame: Up to 24 months after 1st infusion in the combination phase
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Teva Investigational Site 12017
state: California
city: Lake Mary
country: United States
facility: Teva Investigational Site 12021
state: Florida
city: Chicago
country: United States
facility: Teva Investigational Site 12016
state: Illinois
city: Detroit
country: United States
facility: Teva Investigational Site 12015
state: Michigan
city: Huntersville
country: United States
facility: Teva Investigational Site 12014
state: North Carolina
city: Cincinnati
country: United States
facility: Teva Investigational Site 12023
state: Ohio
city: Pittsburgh
country: United States
facility: Teva Investigational Site 12058
state: Pennsylvania
city: Nashville
country: United States
facility: Teva Investigational Site 12019
state: Tennessee
city: Fairfax
country: United States
facility: Teva Investigational Site 12018
state: Virginia
city: Toronto
country: Canada
facility: Teva Investigational Site 11282
state: Ontario
Study officials:
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: