Melanoma Clinical Trial
A Phase 1/2 Study of DCC-3116 as Monotherapy and Combination Therapy in Patients With MAPK Pathway Mutant Solid Tumors
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.
Male or female participants ≥18 years of age
Dose Escalation Phase (Part 1):
Participants must have a histologically confirmed diagnosis of an advanced or metastatic solid tumor with a documented RAS, NF1, or RAF mutations.
Progressed despite standard therapies, and received at least 1 prior line of anticancer therapy.
Participants with a documented mutation in BRAF V600E or V600K must have received approved treatments known to provide clinical benefit prior to study entry.
Participants enrolled in the DCC-3116 and sotorasib cohort (Cohort D) must have a KRAS G12C mutation.
Dose Expansion Phase (Part 2):
Cohort 1: Patients with Pancreatic Ductal Adenocarcinoma (PDAC).
Histologically confirmed PDAC with a documented mutation in KRAS.
Received only 1 prior line of systemic therapy in the advanced or metastatic setting.
Cohort 2: Patients with Non-Small Cell Lung Cancer (NSCLC)
Histologically confirmed NSCLC with a documented mutation in KRAS, NRAS, NF1, or BRAF.
Received at least 2 prior lines but no more than 4 prior lines of systemic therapy in the advanced or metastatic setting.
Cohort 3: Patients with Colorectal Cancer (CRC)
Histologically confirmed CRC with a documented mutation in KRAS, NRAS, NF1, or BRAF.
Received 2-3 prior lines of systemic therapy in the advanced or metastatic setting.
Cohort 4: Patients with Melanoma
Histologically confirmed melanoma with a documented mutation in NRAS.
Received 1-2 prior lines of systemic therapy in the advanced or metastatic setting that included T-cell checkpoint inhibitor-based therapy.
Have not received prior MEK inhibitor therapy.
Cohort 5: Patients with KRAS G12C mutant NSCLC
Histologically confirmed NSCLC with a documented mutation in KRAS G12C.
Received at least 1 prior line but no more than 3 prior lines of systemic therapy in the advanced or metastatic setting.
Have not received prior sotorasib or other KRAS G12C inhibitor therapy.
Must be able to provide tumor tissue sample
Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 (Dose Escalation) or 0 to 1 (Dose Expansion) at Screening
Adequate organ function and bone marrow function.
If a female of childbearing potential must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
Male participants must agree to follow contraception requirements.
Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.
Must not have received the following within the specified time periods prior to the first dose of study drug:
Prior therapies (anticancer or therapies given for other reasons) that are known strong or moderate inhibitors or inducers of CYP3A4 or P-gp including certain herbal medications (eg, St. John's Wort): 14 days or 5× the half-life of the medication (whichever is longer)
All other prior anticancer therapies or any therapy that is investigational for the participant's condition with a known safety and PK profile: 14 days or 5× the half-life of the medication (whichever is shorter)
Investigational therapies with unknown safety and PK profile: 28 days. If there is enough data on the investigational therapy to assess the risk for drug.-drug interactions and late toxicities of prior therapy as low, the Sponsor's Medical Monitor may approve a shorter washout of 14 days
Grapefruit or grapefruit juice: 14 days
Have not recovered from all toxicities from prior therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
Symptomatic central nervous system (CNS) metastases or presence of leptomeningeal disease Note: A participant with previously treated brain metastases may participate provided that they are stable.
New York Heart Association Class III or IV heart disease, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, congestive heart failure, or myocardial infarction within 6 months prior to the first dose of study drug.
Prolongation of the QT interval corrected by Fridericia's formula (QTcF) based on repeated demonstration of QTcF >450 ms in males or >470 ms in females at screening, or history of long QT syndrome.
Left ventricular ejection fraction (LVEF) <50% at Screening
Systemic arterial thrombotic or embolic events
Systemic venous thrombotic events
Bone disease that requires treatment.
Major surgery within 4 weeks of the first dose of study drug. All surgical wounds must be healed and free of infection or dehiscence before the first dose of the study drug.
Any other clinically significant comorbidities.
For participants receiving DCC-3116 and trametinib combination or DCC-3116 and binimetinib combination: previous treatment with trametinib or binimetinib that resulted in treatment discontinuation due to intolerability as a result of an adverse event (AE) that was considered related to trametinib or binimetinib.
For participants receiving DCC-3116 and sotorasib combination in Dose Escalation Part 1: previous treatment with sotorasib that resulted in treatment discontinuation due to intolerability as a result of an adverse event (AE) that was considered related to sotorasib.
For participants receiving DCC-3116 and sotorasib combination: Use of proton pump inhibitors (PPIs) and H2 receptor antagonists that cannot be discontinued 3 days prior to the start of study drug administration.
Known allergy or hypersensitivity to any component of the investigational drug products.
Known human immunodeficiency virus or hepatitis C infection only if the participant is taking medications that are excluded per protocol, active hepatitis B, or active hepatitis C infection.
If female, the participant is pregnant or lactating.
Ongoing participation in an interventional study.
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