A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of RMC-4630 Monotherapy in Adult Participants with Relapsed/Refractory Solid Tumors
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).
* To characterize the safety and tolerability of RMC-4630 monotherapy in participants with relapsed/refractory solid tumors
* To define the MTD, RP2D, and schedule for RMC-4630 monotherapy in participants with relapsed or refractory solid tumors
* To characterize the plasma PK of RMC-4630 after single- and repeat-dose
* To characterize the relationship between plasma PK of RMC-4630 and PD
* To assess PD markers of drug activity, including biochemical markers of SHP2 inhibition in blood or tumor tissue
* To estimate the antitumor effects of RMC-4630 monotherapy at the RP2D in
participants with relapsed/refractory solid tumors harboring specific genotypic
aberrations in the RAS-MAPK pathway
Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Participants in the Dose-Expansion Component (below RP2DS) must have one of the following genotypic aberrations: KRAS amplification, KRASG12C (NSCLC), BRAF Class 3, or NF1 LOF (NSCLC and gynecologic cancers) mutations. For the Dose-Expansion Cohort at the RP2DS, only participants with relapsed or refractory ovarian or endometrial/uterine cancer (or carcinosarcomas) and an NF1 LOF mutation will be allowed. Participants in the QTc substudy may include any genotype and any histotype except pancreatic or colorectal cancer.
Adequate hematologic, hepatic and renal function
Participant able to understand and voluntarily sign the informed consent form (ICF) and able to comply with the study visit schedule and other protocol requirements.
Participants willing to agree to not father a child/become pregnant and comply with effective contraception criteria
Known or suspected leptomeningeal or brain metastases or spinal cord compression
Participants previously treated for these conditions that have had stable central nervous system (CNS) disease, are asymptomatic and off corticosteroids, or are on stable dose of corticosteroids for at least 4 weeks, and have no evidence of clinical or radiographic disease progression over 4-weeks prior to study day 1 are eligible.
Primary central nervous system (CNS) tumors
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
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
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