Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors

• ClinicalTrials.gov Identifier: NCT05732831
• Recruitment Status: Recruiting
• First Posted: February 17, 2023
• Last Update Posted: April 5, 2024
• Sponsor: Tango Therapeutics, Inc.
• Information provided by (Responsible Party): Tango Therapeutics, Inc.

Tracking Information

• First Submitted Date: January 30, 2023
• First Posted Date: February 17, 2023
• Last Update Posted Date: April 5, 2024
• Actual Study Start Date: May 26, 2023
• Estimated Primary Completion Date: May 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 2, 2024)

• Phase 1 Maximum Tolerated Dose [ Time Frame: 28 days ]
  To determine the maximum tolerated dose (MTD) of TNG462
• Phase 1 Dosing Schedule [ Time Frame: 28 days ]
  To determine the dosing schedule of TNG462
• Phase 2 Anti-neoplastic Activity [ Time Frame: 16 weeks ]
  To assess anti-neoplastic activity of TNG462 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1 or mRECIST v1.1

Original Primary Outcome Measures (submitted: February 7, 2023)

• Phase 1 Maximum Tolerated Dose [ Time Frame: 28 days ]
  To determine the maximum tolerated dose (MTD) of TNG462
• Phase 1 Dosing Schedule [ Time Frame: 28 days ]
  To determine the dosing schedule of TNG462
• Phase 2 Anti-neoplastic Activity [ Time Frame: 16 weeks ]
  To assess anti-neoplastic activity of TNG462 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1

Current Secondary Outcome Measures (submitted: January 2, 2024)

• Phase 1 Anti-neoplastic Activity [ Time Frame: 16 weeks ]
  To assess preliminary evidence of anti-neoplastic activity of TNG462 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1 or mRECIST v1.1
• Phase 1 and 2 Adverse Event Profile [ Time Frame: 28 days ]
  To describe the safety and tolerability profile of TNG462 by frequency and severity of AEs
• Phase 1 and 2 Concentration versus Time Curve [ Time Frame: 16 days ]
  Measure the area under the plasma concentration versus time curve (AUC)
• Phase 1 and 2 Time to Achieve Maximal Plasma Concentration [ Time Frame: 16 days ]
  Measure the time to achieve maximal plasma concentration (Tmax)
• Phase 1 and 2 Maximum Observed Plasma Concentration [ Time Frame: 16 days ]
  Measure the maximum observed plasma concentration (Cmax)
• Phase 1 and 2 Terminal Elimination Half-life [ Time Frame: 16 days ]
  Determine the terminal elimination half-life (t1/2)
• Phase 1 and 2 Total Plasma Clearance [ Time Frame: 16 days ]
  Determine the apparent total plasma clearance when dosed orally (CL/F)
• Phase 1 and 2 Volume of Distribution [ Time Frame: 16 days ]
  Determine the apparent volume of distribution when dosed orally (Vz/F)
• Phase 1 and 2 SDMA Levels [ Time Frame: 28 days ]
  SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG462

Original Secondary Outcome Measures (submitted: February 7, 2023)

• Phase 1 Anti-neoplastic Activity [ Time Frame: 16 weeks ]
  To assess preliminary evidence of anti-neoplastic activity of TNG462 in patients with MTAP-deleted advanced solid tumors by RECIST v1.1
• Phase 1 and 2 Safety and Tolerability [ Time Frame: 28 days ]
  To describe the safety and tolerability profile of TNG462 by frequency and severity of AEs
• Phase 1 and 2 Concentration versus Time Curve [ Time Frame: 16 days ]
  Measure the area under the plasma concentration versus time curve (AUC)
• Phase 1 and 2 Time to Achieve Maximal Plasma Concentration [ Time Frame: 16 days ]
  Measure the time to achieve maximal plasma concentration (Tmax)
• Phase 1 and 2 Maximum Observed Plasma Concentration [ Time Frame: 16 days ]
  Measure the maximum observed plasma concentration (Cmax)
• Phase 1 and 2 Terminal Elimination Half-life [ Time Frame: 16 days ]
  Determine the terminal elimination half-life (t1/2)
• Phase 1 and 2 Total Plasma Clearance [ Time Frame: 16 days ]
  Determine the apparent total plasma clearance when dosed orally (CL/F)
• Phase 1 and 2 Volume of Distribution [ Time Frame: 16 days ]
  Determine the apparent volume of distribution when dosed orally (Vz/F)
• Phase 1 and 2 SDMA Levels [ Time Frame: 28 days ]
  SDMA levels in tumor tissue will be assessed pre-treatment and post treatment with TNG462

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Tolerability of TNG462 in Patients With MTAP-deleted Solid Tumors
• Official Title: A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Anti-tumor Activity of TNG462 in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors
• Brief Summary: 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 159 participants.
• 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 in patients with confirmed MTAP-deleted solid tumors. In Phase 2, 5 expansion arms defined by confirmed MTAP-deleted tumor types will enroll in parallel at the RP2D of TNG462. In both parts of the study participants who tolerate the drug may continue treatment until disease progression.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

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)

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Locally Advanced Solid Tumor

Intervention

Drug: TNG462

TNG462, a selective PRMT5 inhibitor, will be administered orally

Study Arms

• Experimental: Dose Escalation
  Participants with MTAP-deleted solid tumors (excluding primary CNS) will receive escalating doses of TNG462 to estimate the MTD
  Intervention: Drug: TNG462
• Experimental: Dose Expansion in NSCLC
  Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D
  Intervention: Drug: TNG462
• Experimental: Dose Expansion in Mesothelioma
  Participants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D
  Intervention: Drug: TNG462
• Experimental: Dose Expansion in Pancreatic Ductal Adenocarcinoma
  Participants with MTAP-deleted pancreatic ductal adenocarcinoma will receive TNG462 at the identified RP2D
  Intervention: Drug: TNG462
• Experimental: Dose Expansion in Sarcoma
  Participants with MTAP-deleted sarcoma (soft tissue or bone) will receive TNG462 at the identified RP2D
  Intervention: Drug: TNG462
• Experimental: Dose Expansion in Solid Tumors
  Participants with other MTAP-deleted solid tumors will receive TNG462 at the identified RP2D
  Intervention: Drug: TNG462

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 7, 2023): 159
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2026
• Estimated Primary Completion Date: May 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. 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:

1. Known allergies, hypersensitivity, or intolerance to TNG462 or its excipients
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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Tango Clinical Trials; (857) 320-4899; clinicaltrials@tangotx.com

• Listed Location Countries: France, Spain, United States

Administrative Information

• NCT Number: NCT05732831
• Other Study ID Numbers: TNG462-C101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Tango Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Tango Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Ellen Hooper, MD; Tango Therapeutics, Inc.

• PRS Account: Tango Therapeutics, Inc.
• Verification Date: April 2024