Title
A Phase 1/2, First-in-Human Study of DCC-3116 as Monotherapy and in Combination with RAS/MAPK Pathway Inhibitors in Patients with Advanced or Metastatic Solid Tumors with RAS/MAPK Pathway Mutations

Description
This is a Phase 1/2, multicenter, open label, first in human (FIH) study of DCC-3116 as monotherapy, and in combination with trametinib, binimetinib, or sotorasib in patients with advanced or metastatic solid tumors with RAS/MAPK pathway mutation. The study consists of 2 parts, a dose-escalation phase, and an expansion phase.

Objective
Primary Objectives:

Dose Escalation Phase (Part 1):
-To evaluate the safety and tolerability of DCC-3116 as monotherapy, in combination with trametinib, in combination with binimetinib, and in combination with sotorasib
-To determine the recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of DCC-3116 as monotherapy
-To determine the RP2D and/or MTD of DCC-3116 in combination with trametinib
-To determine the RP2D and/or MTD of DCC-3116 in combination with binimetinib
-To determine the RP2D and/or MTD of DCC-3116 in combination with sotorasib

Dose Expansion Phase (Part 2):
-To evaluate the objective response rate (ORR) of combination therapy at the RP2D in each Expansion Cohort using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary Objectives:

Dose Escalation Phase (Part 1):
-To evaluate the antitumor activity of DCC-3116 as monotherapy, in combination with trametinib, in combination with binimetinib, and in combination with sotorasib using RECIST v1.1
-To characterize the pharmacokinetics (PK) of DCC-3116 as monotherapy
-To characterize the PK of DCC-3116 and trametinib when administered in combination
-To characterize the PK of DCC-3116 and binimetinib when administered in combination
-To characterize the PK of DCC-3116 and sotorasib when administered in combination

Dose Expansion Phase (Part 2):
-To further characterize the efficacy of DCC-3116 at the RP2D in combination with trametinib, in combination with binimetinib, and in combination with sotorasib in the expansion cohorts
-To further characterize the PK of DCC-3116 and trametinib when administered in combination
-To further characterize the PK of DCC-3116 and binimetinib when administered in combination
-To further characterize the PK of DCC-3116 and sotorasib when administered in combination
-To evaluate the safety and tolerability of DCC-3116 in combination with trametinib
-To evaluate the safety and tolerability of DCC-3116 in combination with binimetinib
-To evaluate the safety and tolerability of DCC-3116 in combination with sotorasib

Treatment Drug: DCC-3116
Drug: Trametinib
Drug: Binimetinib
Drug: Sotorasib

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Anal; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Hematologic cancers, other; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital