dose escalation of rmc-4630 monotherapy in relapsed/refractory solid tumors

Conditions: Solid Tumors

Summary: 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).

this is an open-label, multicenter, phase 1 study of oral rmc-4630 monotherapy in participants with advanced relapsed or refractory solid tumors. the study will include 2 components: 1) a dose-escalation component for participants with relapsed or refractory solid tumors and 2) a dose-expansion component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the ras-mapk pathway. participants will be treated until disease progression per recist v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

Eligibility criteria:
inclusion criteria: * participant (male or female) ≥18 years of age * 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 must have one of the following genotypic aberrations: kras amplifications, krasg12c (nsclc), braf class 3, or nf1 lof (nsclc and gynecological cancers) mutations * 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 exclusion criteria: * known or suspected leptomeningeal or brain metastases or spinal cord compression * 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 * females who are pregnant or breastfeeding

Keywords: shp2 ptpn11 nsclc egfr kras g12 braf class 3 nf1 lof advanced solid tumor advanced solid malignancies melanoma skin cancer ovarian cancer endometrium/uterus cancer bladder cancer cervical cancer carcinoma, non-small-cell lung neoplasms, squamous cell carcinoma, squamous cell esophageal neoplasms carcinoma, bronchogenic bronchial neoplasms lung neoplasms respiratory tract neoplasms thoracic neoplasms neoplasms by site neoplasms lung diseases respiratory tract diseases neoplasms, glandular and epithelial gastrointestinal neoplasms digestive system neoplasms head and neck neoplasms digestive system diseases esophageal diseases gastrointestinal diseases