A Safety, Tolerability and PK Study of DCC-3116 in Patients With RAS or RAF Mutant Advanced or Metastatic Solid Tumors.

• Status: Recruiting
• Trial end date: 2024-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1, multicenter, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, clinical activity, pharmacokinetics (PK), and pharmacodynamics (PD) of DCC-3116 as a single agent and in combination with trametinib in patients with advanced or metastatic solid tumors with RAS or RAF mutations. The study consists of 2 parts, a dose-escalation phase, and an expansion phase.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Deciphera Pharmaceuticals LLC
• Treatments: Trametinib

Criteria

Inclusion Criteria:

1. Male or female participants ≥18 years of age at the time of informed consent.

2. Dose Escalation Phase:

1. Participants must have a histologically confirmed diagnosis of an advanced or metastatic solid tumor with a documented RAS or RAF mutation.

2. 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.

3. Dose Expansion Phase:

1. Cohort 1: Pancreatic Ductal Adenocarcinoma.

• Histologically confirmed PDAC with a documented mutation in KRAS or BRAF.

• Received at least 1 prior line but no more than 3 prior lines of systemic therapy in the advanced or metastatic setting.

2. Cohort 2: Non-Small Cell Lung Cancer

• Histologically confirmed NSCLC with a documented mutation in KRAS, NRAS, or BRAF.

• Received at least 2 prior lines but no more than 4 prior lines of systemic therapy in the advanced or metastatic setting.

3. Cohort 3: Colorectal Cancer

• Histologically confirmed CRC with a documented mutation in KRAS, NRAS, or BRAF.

• Received at least 2 prior lines of systemic therapy in the advanced or metastatic setting.

4. Cohort 4: Melanoma

• Histologically confirmed melanoma with a documented mutation in NRAS or BRAF.

• Received at least 2 prior lines but no more than 4 prior lines of systemic therapy in the advanced or metastatic setting.

4. Must be able to provide tumor tissue sample

5. Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 at Screening

6. Adequate organ function and bone marrow function.

7. If a female of childbearing potential must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.

8. Male participants must agree to follow contraception requirements.

9. Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.

Exclusion Criteria:

1. Received prior anticancer therapy, including investigational therapy within 2 weeks or 5 × the half-life (whichever is shorter) prior to the first dose of study drug.

2. Have not recovered from all toxicities from prior therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).

3. 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.

4. 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.

5. 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.

6. Left ventricular ejection fraction (LVEF) <50% at Screening

7. Systemic arterial thrombotic or embolic events

8. Systemic venous thrombotic events

9. A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy including uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes.

10. Concurrent neuromuscular disorder that is associated with the potential of elevated creatine kinase.

11. Bone disease that requires treatment.

12. 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.

13. Any other clinically significant comorbidities.

14. For participants receiving DCC-3116 and trametinib combination: previous treatment with trametinib that resulted in treatment discontinuation due to intolerability as a result of an adverse event (AE) that was considered related to trametinib.

15. Known allergy or hypersensitivity to any component of the investigational drug product.

16. 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.

17. If female, the participant is pregnant or lactating.

18. Ongoing or prior participation in an investigational drug study within 30 days of screening.