Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors
Purpose
This is a first in human study in patients with advanced or metastatic solid tumors known to have an MTAP deletion. The first part of the study is an open-label, dose escalation and the second part is an open label dose expansion in specific MTAP-deleted tumor types. The study drug, TNG462, is a selective PRMT5 inhibitor administered orally. The study is planned to treat up to 225 participants.
Condition
- Locally Advanced Solid Tumor
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Age: ≥18 years-of-age at the time of signature of the main study ICF 2. Performance status: ECOG Performance Score of 0 to 1 3. Confirmed histologic or cytologic diagnosis of a locally advanced, metastatic, and/or unresectable solid tumor 4. Prior standard therapy, as available 5. Documented bi-allelic (homozygous) deletion of MTAP in a tumor detected by next- generation sequencing or absence of MTAP protein in a tumor detected by IHC. 6. Adequate organ function/reserve per local labs 7. Adequate liver function per local labs 8. Adequate renal function per local labs 9. Negative serum pregnancy test result at screening 10. Written informed consent must be obtained according to local guidelines
Exclusion Criteria
- Known allergies, hypersensitivity, or intolerance to TNG462, or its excipients or to pembrolizumab in the combination treatment arms 2. Uncontrolled intercurrent illness that will limit compliance with the study requirements 3. Active infection requiring systemic therapy 4. Currently participating in or has planned participation in a study of another investigational agent or device 5. Impairment of GI function or disease that may significantly alter the absorption of oral TNG462 6. Active prior or concurrent malignancy. 7. Central nervous system metastases associated with progressive neurological symptoms 8. Current active liver disease from any cause 9. Known to be HIV positive, unless all of the following criteria are met: 1. CD4+ count ≥300/μL 2. Undetectable viral load 3. Receiving highly active antiretroviral therapy 10. Clinically relevant cardiovascular disease 11. A female patient who is pregnant or lactating 12. Patient is unwilling or unable to comply with the scheduled visits, drug administration plan, laboratory tests, biopsy, or other study procedures and study restrictions 13. Patient has a prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, may affect the safety of the patient or impair the assessment of study results
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Phase 1 dose escalation (sequential) followed by phase 2 dose expansion in 5 arms (parallel)
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Dose Escalation |
Participants with MTAP-deleted solid tumors (excluding primary CNS) will receive escalating doses of TNG462 single agent and in combination with pembrolizumab to estimate the MTD |
|
|
Experimental Dose Expansion in NSCLC |
Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D(s) |
|
|
Experimental Dose Expansion in Mesothelioma |
Participants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D(s) |
|
|
Experimental Dose Expansion in Pancreatic Ductal Adenocarcinoma |
Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D(s) |
|
|
Experimental Dose Expansion in Sarcoma |
Participants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D(s) |
|
|
Experimental Dose Expansion in Solid Tumors |
Participants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s) |
|
|
Experimental Dose Expansion in NSCLC in Combination with Pembrolizumab |
Participants NSCLC (squamous and non squamous) MTAP-deleted solid tumors will receive TNG462 at the identified RP2D(s) |
|
Recruiting Locations
Massachusetts General Hospital
Boston, Massachusetts 02214
Boston, Massachusetts 02214
Contact:
Ibiayi Dagogo-Jack, MD
Ibiayi Dagogo-Jack, MD
More Details
- Status
- Recruiting
- Sponsor
- Tango Therapeutics, Inc.
Detailed Description
This is a Phase 1/2 multi-center, open label study in solid tumor patients who have a confirmed homozygous MTAP deletion in their tumor. The Phase 1 portion is a dose escalation study of oral TNG462 administered as a single agent and in combination with pembrolizumab in patients with confirmed MTAP-deleted solid tumors. In Phase 2, 6 expansion arms defined by confirmed MTAP-deleted tumor types will enroll in parallel at the RP2D(s) of TNG462 and in combination. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.