First-in-human, Phase 1/2, open-label, multicenter, dose-escalation and expansion study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tango Therapeutics Inc., Tango Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Aug 2023 → ongoing

Decision date (initial)

2023-06-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2022-502645-99-00

ClinicalTrials.gov

NCT05732831

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy, Therapy, Dose response, Pharmacodynamic

Phase 1: To determine the MTD and RP2D(s) of TNG462 when administered as single agent and in combination with pembrolizumab
Phase 2: To assess antineoplastic activity of TNG462 in participants with MTAP-deleted advanced solid tumors when administered as a single agent and in combination with pembrolizumab

Secondary objectives 2

1. Phase 1: To assess preliminary evidence of antineoplastic activity of TNG462 when administered as single agent and in combination with pembrolizumab in participants with MTAP-deleted advanced solid tumors
2. Phase 1 and 2: - To describe the safety and tolerability profile of TNG462 as a single agent and when administered in combination with pembrolizumab - To characterize the PK profile of TNG462 as a single agent and when administered in combination with pembrolizumab - To characterize the PK profile of pembrolizumab when administered in combination with TNG462 - To assess the PD of TNG462 in participants with MTAP-deleted solid tumors

Conditions and MedDRA coding

MTAP-deleted Advanced or Metastatic Solid Tumors

Study design 6 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Age: ≥18 years-of-age at the time of signature of the main study ICF
2. 2. Performance status: ECOG Performance Score of 0 to 1
3. 3. Confirmed histologic or cytologic diagnosis of a locally advanced, metastatic, and/or unresectable solid tumor
4. 4. Prior standard therapy, as available
5. 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. 6. Adequate organ function/reserve per local labs
7. 7. Adequate liver function per local labs
8. 8. Adequate renal function per local labs
9. 9. Negative serum pregnancy test result at screening
10. 10. Written informed consent must be obtained according to local guidelines

Exclusion criteria 13

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. Adequate liver function per local labs
8. Current active liver disease from any cause
9. Known to be HIV positive, unless all of the following criteria are met: a. CD4+ count ≥300/μL b. Undetectable viral load c. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Phase 1: • Incidence of DLTs within the first 28 days of treatment with TNG462 as a single agent • Incidence of DLTs within the first 21 days of treatment with TNG462 plus pembrolizumab Phase 2: • ORR (CR + PR) as determined by RECIST v1.1, mRECIST v1.1, or iRECIST per investigator assessment • DOR as determined by RECIST v1.1, mRECIST v1.1 or iRECIST per investigator assessment • PFS by investigator assessment • CBR (CR + PR + stable disease) at 16 weeks

Secondary endpoints 2

1. Phase 1: • ORR (CR + PR) as determined by RECIST v1.1, mRECIST v1.1 or iRECIST, per investigator assessment • DOR as determined by RECIST v1.1, mRECIST v1.1 or iRECIST,per investigator assessment • PFS by investigator assessment • CBR (CR + PR + stable disease) at 16 weeks for patients treated with single agent or at 18 weeks for patients treated with the pembrolizumab combination
2. Phase 1 and 2: Type, frequency, severity, timing, and relationship to study treatment of any AEs, SAEs, and changes in vital signs, ECGs, and safety laboratory tests PK parameters of TNG462 Pre-treatment and trough pembrolizumab concentrations Changes in SDMA levels in tumor after dosing with TNG462

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tango Therapeutics Inc.

Sponsor organisation

Tango Therapeutics Inc.

Address

100 Binney Street Ste 700

City

Cambridge

Postcode

02142-1096

Country

United States

Scientific contact point

Organisation

Tango Therapeutics Inc.

Contact name

Kirsten Overoye-Chan

Public contact point

Organisation

Tango Therapeutics Inc.

Contact name

Kirsten Overoye-Chan

Tango Therapeutics Inc.

Sponsor organisation

Tango Therapeutics Inc.

Address

201 Brookline Avenue Suite 901

City

Boston

Postcode

02215-4159

Country

United States

Scientific contact point

Organisation

Tango Therapeutics Inc.

Contact name

Kirsten Overoye-Chan

Public contact point

Organisation

Tango Therapeutics Inc.

Contact name

Kirsten Overoye-Chan

Third parties 14

Locations

2 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

17 submissions — initial application plus substantial / non-substantial modifications