RMC-4630-02: A Phase 1b/2, Open-Label, Multicenter Dose-Escalation and Dose-Expansion Study of the Combination of RMC-4630 and Cobimetinib in Adult Participants with Relapsed/Refractory Solid Tumors with Specific Genomic Aberrations

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and
pharmacodynamic (PD) profiles of RMC-4630 and cobimetinib in adult participants with
relapsed/refractory solid tumors with specific genomic aberrations and to identify the
recommended Phase 2 dose (RP2D); and to evaluate the safety, tolerability, pharmacokinetic
(PK), and pharmacodynamic (PD) profiles of RMC-4630 and osimertinib in adult participants with
EGFR mutation-positive locally advanced or metastatic NSCLC.

Inclusion Criteria:

- Age ≥18 years

- For RMC-4630 + Cobimetinib only - Participants who have advanced solid tumors that
have failed, are intolerant to, or are considered ineligible for standard of care
anti-cancer treatments including approved drugs for oncogenic drivers in their tumor
type.

- For RMC-4630 + Osimertinib only - Locally advanced or metastatic EGFR mutant NSCLC not
amenable to curative surgery or radiotherapy

- For RMC-4630 + Cobimetinib only - Participants must have one of the following
genotypic aberrations: KRAS mutations and amplifications, BRAF Class 3 mutations, or
NF1 LOF mutations

- For RMC-4630 + Osimertinib only - Evidence of radiological documentation of
progression with osimertinib monotherapy or an osimertinib containing regimen.
Participants should not be considered a current candidate for 1st generation EGFR
TKI's by the investigator.

- Eastern Cooperative Oncology Group (ECOG) performance status of ≤1

- Adequate hematological, hepatic, and renal function

- Capable of giving signed informed consent form (ICF). Willing and able to compile with
study requirements and restrictions

- Life expectancy >12 weeks

- Female of childbearing potential and males with partners of childbearing potential
must comply with effective contraception criteria .

Exclusion Criteria:

- Primary central nervous system (CNS) tumors.

- Known or suspected leptomeningeal or brain metastases or spinal cord compression.

- For RMC-4630 + osimertinib arm only - Known or suspected Small cell, squamous, or
pleomorphic lung transformations

- Clinically significant cardiac disease

- Active, clinically significant interstitial lung disease or pneumonitis

- History or current evidence of retinal pigment epithelial detachment (RPED), central
serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or
RVO

- Known HIV infection or active/chronic hepatitis B or C infection.

- Any other unstable or clinically significant concurrent medical condition that would,
in the opinion of the investigator, jeopardize the safety of a participant, impact
their expected survival through the end of the study participation, and/or impact
their ability to comply with the protocol prior/concomitant therapy

- Females who are pregnant or breastfeeding