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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

Phase 1
Recruiting
Conditions
Advanced Solid Tumors
Interventions
Registration Number
NCT06480552
Lead Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
240
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
TEV-56278 in Combination with Pembrolizumab; Dose EscalationTEV-56278-
TEV-56278 Monotherapy; Dose EscalationTEV-56278-
TEV-56278 Monotherapy; Dose ExpansionTEV-56278-
TEV-56278 in Combination with Pembrolizumab; Dose EscalationPembrolizumab-
Primary Outcome Measures
NameTimeMethod
Incidence of SAEs in the escalation phaseUp to 15 months after 1st infusion in the escalation phase
Incidence of AEs meeting protocol-defined DLT criteria in the escalation phaseUp to 28 days after 1st infusion in the escalation phase

DLT: dose-limiting toxicity

Incidence of AEs leading to discontinuation in the escalation phaseUp to 12 months after 1st infusion in the escalation phase
Duration of Response (DOR) in the expansion phaseUp to 24 months after the 1st dose in the expansion phase
Incidence of AEs with CTCAE Grade≥3 in the escalation phaseUp to 15 months after 1st infusion in the escalation phase

CTCAE: Common Terminology Criteria for Adverse Events

Incidence of dose modifications due to AEs in the escalation phaseUp to 12 months after 1st infusion in the escalation phase
Recommended Phase 2 dose as monotherapyUp to 24 months after 1st infusion
Objective Response Rate (ORR) based on RECIST criteria in the expansion phaseUp to 24 months after the 1st dose in the expansion phase

RECIST: Response Evaluation Criteria in Solid Tumors.

Recommended Phase 2 dose in combination with PembrolizumabUp to 24 months after 1st dose
Incidence of AEs with CTCAE Grade≥3 in the combination phaseUp to 15 months after 1st infusion in the combination phase
Incidence of SAEs in the combination phaseUp to 15 months after 1st infusion in the combination phase
Incidence of AEs meeting protocol-defined DLT criteria in the combination phaseUp to 28 days after 1st infusion in the combination phase
Incidence of AEs leading to discontinuation in the combination phaseUp to 12 months after 1st infusion in the combination phase
Incidence of dose modifications due to AEs in the combination phaseUp to 12 months after 1st infusion in the combination phase
Secondary Outcome Measures
NameTimeMethod
Incidence of AEs with CTCAE Grade≥3 in the expansion phaseUp to 24 months after 1st infusion in the expansion phase
Incidence of AEs leading to discontinuation in the expansion phaseUp to 12 months after 1st infusion in the expansion phase
Disease Control Rate (DCR) according to RECIST (v1.1) criteriaUp to 24 months after 1st infusion
Time to Respond (TTR) according to RECIST (v1.1) criteriaUp to 24 months after 1st infusion
AUC0-lastPredose up to Day 8

Area under the serum concentration-time curve from time 0 to last measurable drug concentration

tmaxPredose up to Day 8

Time to maximum observed drug concentration

Incidence of dose modifications due to AEs in the expansion phaseUp to 12 months after 1st infusion in the expansion phase
Objective Response Rate (ORR) based on RECIST criteria in the escalation phaseUp to 24 months after 1st infusion in the escalation phase
Incidence of SAEs in the expansion phaseUp to 15 months after 1st infusion in the expansion phase
Objective Response Rate (ORR) based on RECIST criteria in the combination phaseUp to 24 months after 1st infusion in the combination phase
CmaxPredose up to Day 8

Maximum observed concentration

Trial Locations

Locations (10)

Teva Investigational Site 12017

🇺🇸

Los Angeles, California, United States

Teva Investigational Site 12021

🇺🇸

Lake Mary, Florida, United States

Teva Investigational Site 12016

🇺🇸

Chicago, Illinois, United States

Teva Investigational Site 12015

🇺🇸

Detroit, Michigan, United States

Teva Investigational Site 12014

🇺🇸

Huntersville, North Carolina, United States

Teva Investigational Site 12058

🇺🇸

Pittsburgh, Pennsylvania, United States

Teva Investigational Site 12019

🇺🇸

Nashville, Tennessee, United States

Teva Investigational Site 12018

🇺🇸

Fairfax, Virginia, United States

Teva Investigational Site 11282

🇨🇦

Toronto, Ontario, Canada

Teva Investigational Site 12023

🇺🇸

Cincinnati, Ohio, United States

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