A Study of IMM-6-415 in RAS/RAF Mutant Solid Tumors

Brief summary public domain (ClinicalTrials.gov)

This is a FIH, ascending dose study to characterize the safety, tolerability, optimal dose and preliminary anti-tumor activity of IMM-6-415 in participants with advanced or metastatic solid tumors harboring RAS or RAF oncogenic mutations.

Detailed description public domain (ClinicalTrials.gov)

The dose exploration will identify the candidate recommended Phase 2 dose (RP2D) of IMM-6-415 to further explore the anti-tumor activity of IMM-6-415 as monotherapy in Phase 2a tumor-specific cohorts. Patients will be self-administering IMM-6-415 on a daily basis for up to 16 cycles (21-day cycles). During the first 2 cycles, PK and PD will be assessed. Solid tumor types with RAS/RAF mutations are eligible.

Intervention public domain (ClinicalTrials.gov)

Drug: IMM-6-415. Twice daily, oral tablet administered in 21-day cycles until treatment discontinuation criteria are met.

Arm public domain (ClinicalTrials.gov)

IMM-6-415 (experimental): Dose Escalation and Dose Expansion

Primary outcome public domain (ClinicalTrials.gov)

Phase 1/2a: Adverse Events. Number of participants with adverse events Time frame: From treatment initiation through 30 days following the last IMM-6-415 dose.

Primary outcome public domain (ClinicalTrials.gov)

Phase 1: Dose-Limiting Toxicities (DLT). Number of participants with dose-limiting toxicities Time frame: The first 21 days of study treatment.

Primary outcome public domain (ClinicalTrials.gov)

Phase 1: Recommended Phase 2 Dose (RP2D) candidate. Selection of candidate RP2D to take forward into Ph2a Time frame: Initiation of study treatment through 21 days (up to approximately 18 months).

Primary outcome public domain (ClinicalTrials.gov)

Phase 1: Maximum Observed Plasma Concentration of IMM-6-415. Cmax Time frame: After 9 weeks (3 Cycles) of study treatment.

Primary outcome public domain (ClinicalTrials.gov)

Phase 1: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415. Tmax Time frame: After 9 weeks (3 Cycles) of study treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 2a: Maximum Observed Plasma Concentration of IMM-6-415. Time frame: After 9 weeks (3 Cycles) of study treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 2a: Time to Reach Maximum Observed Plasma Concentration of IMM-6-415. Time frame: After 9 weeks (3 Cycles) of study treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 2a: Area Under Plasma Concentration (AUC) Time Curve of IMM-6-415. Time frame: After 9 weeks (3 Cycles) of study treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 2a: Disease Control Rate (DCR). Time frame: After 12 weeks (4 Cycles) of study treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 2a: Progression Free Survival (PFS). Time frame: Up to approximately 2 years.

Secondary outcome public domain (ClinicalTrials.gov)

Phase 2a: Duration of Response (DOR). Time frame: Up to approximately 2 years.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Age ≥18 years * Life expectancy \>16 weeks * Part 1: Histologically or cytologically confirmed diagnosis of a locally advanced unresectable or metastatic solid tumor malignancy harboring RAS (NRAS, KRAS, or HRAS)- or RAF- (ARAF, BRAF, RAF1) activating mutations, as documented by genomic analysis. Results of mutation analysis must be available prior to participant enrollment. A prior genomics report from archival tissues or liquid biopsy demonstrating mutation is acceptable * Part 2: Histologically or cytologically confirmed diagnosis of one of the following locally advanced unresectable or metastatic solid tumor malignancies: pancreatic adenocarcinoma, RASmut melanoma, Class I BRAFmut melanoma, RASmut NSCLC, other RASmut GI cancers (aside from CRC) or any other RAFmut solid tumor as documented by genomic analysis. Results of mutation analysis must be available prior to participant enrollment. A prior genomics report from archival tissues or liquid biopsy demonstrating mutation is acceptable * Participants must have received at least 1 line of systemic standard-of-care treatment for their advanced or metastatic disease and in the assessment of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from other treatment options * Participants previously treated with codon-specific inhibitors of KRAS (including investigational agents) are eligible * KRASG12C mutant participants must have received prior treatment with a KRASG12C inhibitor for any approved indication * Radiologic evidence of measurable disease (i.e., at least 1 target lesion) according to RECIST 1.1 criteria * ECOG performance status 0 or 1. * Participant has adequate organ function Exclusion Criteria: * Inability to swallow oral medications. * Symptomatic, untreated, or actively progressing known central nervous system metastases. * Uncontrolled pleural or pericardial effusion or ascites requiring repeated drainage more than once every 28 days. In dwelling catheters are allowed. * History of severe COVID-19 infection resulting in current need of supplemental O2 therapy to maintain resting oxygen saturations ≥90%. * Presence of ongoing toxicities related to prior anticancer therapy that have not resolved to Grade ≤1 and are not otherwise allowed * Impaired cardiac function or clinically significant cardiac disease * Uncontrolled intercurrent illness including but not limited to poorly controlled diabetes or any medical condition determined …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 30 participants (actual).