A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of TNG348 Single Agent and in Combination with a PARP Inhibitor in Patients with BRCA ½ Mutant or Other HRD+ Advanced or Metastatic Solid Tumors.

The goal of this interventional clinical trial is to learn about TNG348, a ubiquitin
specific peptidase 1 (USP1) inhibitor, alone and in combination with olaparib in patients
with BRCA 1/2 mutant or HRD+ solid tumors.

The main question[s] it aims to answer are:

- to evaluate the safety and tolerability of single agent and combination therapy

- to determine the recommended dose for Phase 2 of single agent and combination
therapy

- to determine the pharmacokinetics of TNG348 as a single agent and in combination
therapy

- to evaluate the initial antineoplastic activity as a single agent and in combination
therapy

Participants will receive study treatment until they experience an undesirable side
effect, their disease progresses or until they withdraw consent.

Inclusion Criteria:

- Is ≥18 years of age at the time of signature of the main study ICF.

- Has ECOG performance status of 0 or 1.

- Has advanced or metastatic solid tumor with measurable disease based on RECIST v1.1.

- All participants must have documented BRCA 1/2 mutant or other HRD+ in solid tumor,
which is identified through a validated sequencing test

- Adequate organ and bone marrow function per local labs

- Negative serum pregnancy test result at screening

- Written informed consent must be obtained according to local guidelines

Exclusion Criteria:

- Known allergies, hypersensitivity, or intolerance to TNG348, olaparib or its
excipients

- Uncontrolled intercurrent illness that will limit compliance with the study
requirements

- Currently participating in or has planned participation in a study of another
investigational agent or device

- Impairment of GI function or disease that may significantly alter the absorption of
study drug

- Active prior or concurrent malignancy.

- Central nervous system metastases associated with progressive neurological symptoms

- Participant with MDS

- Clinically relevant cardiovascular disease

- Participant with known active or chronic infection

- A female patient who is pregnant or lactating