Advanced Solid Tumors
Conditions
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 (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).
Interventions
DRUGTEV-56278
Administered intravenously
DRUGPembrolizumab
Administered intravenously
Sponsors
Teva Branded Pharmaceutical Products R&D LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of AEs with CTCAE Grade≥3 in the escalation phase | Up to 15 months after 1st infusion in the escalation phase | CTCAE: Common Terminology Criteria for Adverse Events |
| Incidence of SAEs in the escalation phase | Up to 15 months after 1st infusion in the escalation phase | — |
| Incidence of AEs meeting protocol-defined DLT criteria in the escalation phase | Up to 28 days after 1st infusion in the escalation phase | DLT: dose-limiting toxicity |
| Incidence of dose modifications due to AEs in the escalation phase | Up to 12 months after 1st infusion in the escalation phase | — |
| Incidence of AEs leading to discontinuation in the escalation phase | Up to 12 months after 1st infusion in the escalation phase | — |
| Recommended Phase 2 dose as monotherapy | Up to 24 months after 1st infusion | — |
| Objective Response Rate (ORR) based on RECIST (v 1.1) criteria in the expansion phase | Up to 24 months after the 1st dose in the expansion phase | RECIST: Response Evaluation Criteria in Solid Tumors. |
| Duration of Response (DOR) in the expansion phase | Up to 24 months after the 1st dose in the expansion phase | — |
| Recommended Phase 2 dose in combination with Pembrolizumab | Up to 24 months after 1st dose | — |
| Incidence of AEs with CTCAE Grade≥3 in the combination phase | Up to 15 months after 1st infusion in the combination phase | — |
| Incidence of SAEs in the combination phase | Up to 15 months after 1st infusion in the combination phase | — |
| Incidence of AEs meeting protocol-defined DLT criteria in the combination phase | Up to 28 days after 1st infusion in the combination phase | — |
| Incidence of dose modifications due to AEs in the combination phase | Up to 12 months after 1st infusion in the combination phase | — |
| Incidence of AEs leading to discontinuation in the combination phase | Up to 12 months after 1st infusion in the combination phase | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-last | Predose up to Day 8 | Area under the serum concentration-time curve from time 0 to last measurable drug concentration |
| Cmax | Predose up to Day 8 | Maximum observed concentration |
| tmax | Predose up to Day 8 | Time to maximum observed drug concentration |
| Objective Response Rate (ORR) based on RECIST (v1.1) criteria in the escalation phase | Up to 24 months after 1st infusion in the escalation phase | — |
| Incidence of AEs with CTCAE (v5.0) Grade≥3 in the expansion phase | Up to 24 months after 1st infusion in the expansion phase | — |
| Incidence of SAEs in the expansion phase | Up to 15 months after 1st infusion in the expansion phase | — |
| Incidence of dose modifications due to AEs in the expansion phase | Up to 12 months after 1st infusion in the expansion phase | — |
| Incidence of AEs leading to discontinuation in the expansion phase | Up to 12 months after 1st infusion in the expansion phase | — |
| Disease Control Rate (DCR) according to RECIST (v1.1) criteria | Up to 24 months after 1st infusion | — |
| Time to Respond (TTR) according to RECIST (v1.1) criteria | Up to 24 months after 1st infusion | — |
| Objective Response Rate (ORR) based on RECIST criteria in the combination phase | Up to 24 months after 1st infusion in the combination phase | — |
Countries
Canada, United States
Contacts
CONTACTTeva U.S. Medical Information
STUDY_DIRECTORTeva Medical Expert, MD
Teva Branded Pharmaceutical Products R&D LLC
Outcome results
None listed