A Phase 1/2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Antitumor Activity of TNG462 in Combination with Other Agents in Patients with Pancreatic Cancer with MTAP Loss; and Pancreatic or Non-Small Cell Lung Cancer with MTAP Loss and RAS Mutation

TNG462-C102 is a Phase 1/2, open-label, multicenter study designed to determine the
safety, tolerability, PK, PD, and preliminary antineoplastic activity of oral TNG462 in
combination with RMC-6236, RMC-9805, mFOLFIRINOX or gemcitabine/nab-paclitaxel. The study
comprises a dose escalation phase and a dose expansion phase.

Inclusion Criteria:

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

2. Has an ECOG PS of 0 or 1.

3. Has a tumor with loss of MTAP protein or bi-allelic deletion of the MTAP gene

4. Arms A and B only: Has a tumor with a RAS mutation

5. Pathologically documented metastatic PDAC or locally advanced, recurrent or
metastatic NSCLC

6. Has received prior standard therapy

7. Arms A and B only: Must not have received prior RAS-targeted therapy

8. Has evidence of measurable disease based on RECIST v1.1.

9. Adequate organ function

10. Must be able to swallow tablets.

11. Negative pregnancy test at screening

12. Written informed consent must be obtained according to local guidelines

Exclusion Criteria:

1. Has received prior treatment with a PRMT5 inhibitor, or MAT2A inhibitor

2. Arms A and B only: Prior enrollment in any phase 3 clinical trial of RMC-6236 or
RMC-9805

3. Known allergy, hypersensitivity or intolerance to TNG462 (all arms), RMC-6236 Arm
A), RMC-9805 (Arm B), mFOLFIRINOX (Arm C), gemcitabine/nab-paclitaxel (Arm D) or
their excipients

4. Has uncontrolled intercurrent illness that will limit compliance with the study
requirements.

5. Has an active infection requiring systemic therapy.

6. Is currently participating in or has planned concurrent participation in a study of
another investigational agent or device.

7. Has impairment of GI function or disease that may significantly alter the absorption
of the oral medications

8. Has known or suspected active or untreated CNS metastases associated with
progressive neurological symptoms

9. Has current active liver disease from any cause

10. Is known to be HIV positive, unless all the following criteria are met:

1. CD4+ count ≥300/µL.

2. Undetectable viral load.

3. Receiving highly active antiretroviral therapy

11. Has clinically relevant cardiovascular disease

12. History of or presence of active interstitial lung disease

13. Is a female patient who is pregnant or lactating

14. Is unwilling or unable to comply with the scheduled visits, study treatment
administration plan, laboratory tests or other study procedures and study
restrictions.

15. 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 ability to assess study
results