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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05732831
Recruitment Status : Not yet recruiting
First Posted : February 17, 2023
Last Update Posted : February 21, 2023
Sponsor:
Information provided by (Responsible Party):
Tango Therapeutics, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Locally Advanced Solid Tumor Drug: TNG462 Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 159 participants
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
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
Estimated Study Start Date : April 2023
Estimated Primary Completion Date : May 2026
Estimated Study Completion Date : September 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose Escalation
Participants with MTAP-deleted solid tumors will receive escalating doses of TNG462 to estimate the MTD
 Drug: TNG462
TNG462, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in NSCLC
Participants with MTAP-deleted NSCLC (squamous and non squamous) will receive TNG462 at the identified RP2D
 Drug: TNG462
TNG462, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in Mesothelioma
Participants with MTAP-deleted mesothelioma will receive TNG462 at the identified RP2D
 Drug: TNG462
TNG462, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in Cholangiocarcinoma
Participants with MTAP-deleted cholangiocarcinoma will receive TNG462 at the identified RP2D
 Drug: TNG462
TNG462, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in MPNST
Participants with MTAP-deleted malignant peripheral nerve sheath tumor (MPNST) will receive TNG462 at the identified RP2D
 Drug: TNG462
TNG462, a selective PRMT5 inhibitor, will be administered orally
Experimental: Dose Expansion in solid tumors
Participants with MTAP-deleted solid tumors will receive TNG462 at the identified RP2D
 Drug: TNG462
TNG462, a selective PRMT5 inhibitor, will be administered orally


Outcome Measures
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Primary Outcome Measures :
  1. Phase 1 Maximum Tolerated Dose [ Time Frame: 28 days ]
    To determine the maximum tolerated dose (MTD) of TNG462

  2. Phase 1 Dosing Schedule [ Time Frame: 28 days ]
    To determine the dosing schedule of TNG462

  3. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Phase 1 and 2 Concentration versus Time Curve [ Time Frame: 16 days ]
    Measure the area under the plasma concentration versus time curve (AUC)

  4. Phase 1 and 2 Time to Achieve Maximal Plasma Concentration [ Time Frame: 16 days ]
    Measure the time to achieve maximal plasma concentration (Tmax)

  5. Phase 1 and 2 Maximum Observed Plasma Concentration [ Time Frame: 16 days ]
    Measure the maximum observed plasma concentration (Cmax)

  6. Phase 1 and 2 Terminal Elimination Half-life [ Time Frame: 16 days ]
    Determine the terminal elimination half-life (t1/2)

  7. Phase 1 and 2 Total Plasma Clearance [ Time Frame: 16 days ]
    Determine the apparent total plasma clearance when dosed orally (CL/F)

  8. Phase 1 and 2 Volume of Distribution [ Time Frame: 16 days ]
    Determine the apparent volume of distribution when dosed orally (Vz/F)

  9. 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


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05732831


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

Sponsors and Collaborators
Tango Therapeutics, Inc.
Investigators
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Study Director: Ron Weitzman, MD Tango Therapeutics, Inc.
More Information
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Responsible Party: Tango Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05732831    
Other Study ID Numbers: TNG462-C101
First Posted: February 17, 2023    Key Record Dates
Last Update Posted: February 21, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tango Therapeutics, Inc.:
MTAP deletion
PRMT5
cholangiocarcinoma
NSCLC
 mesothelioma
MPNST
Tango
pancreatic
Additional relevant MeSH terms:
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Neoplasms