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
- Trial ID
- 2022-501474-19-00
- Protocol
- DCC-3116-01-001
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **objective response rate (ORR)** of combination therapy at the recommended phase 2 dose (RP2D) in each expansion cohort using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. This is clinically relevant as it aims to determine the efficacy of the combination therapy in treating patients with advanced or metastatic solid tumors harboring RAS/MAPK pathway mutations, which include conditions such as pancreatic ductal adenocarcinoma, colorectal cancer, melanoma, non-small cell lung cancer, and other advanced solid tumors.
Secondary objectives include:
- To further characterize the efficacy of **DCC-3116** at the RP2D in combination with trametinib, binimetinib, and sotorasib in the expansion cohorts.
- To further characterize the pharmacokinetics (PK) of DCC-3116 when administered in combination with trametinib, binimetinib, and sotorasib.
- To evaluate the safety and tolerability of DCC-3116 in combination with trametinib, binimetinib, and sotorasib.
Participants
The clinical trial involves a total of **73 participants** diagnosed with various conditions, including **Pancreatic Ductal Adenocarcinoma**, **Colorectal Cancer**, **Melanoma**, **Metastatic Solid Tumor**, **Advanced Solid Tumor**, and **Non-Small Cell Lung Cancer**. The study population comprises both male and female subjects, aged 18 years and older, who have progressed despite standard therapies or for whom conventional therapy is not considered effective or tolerable. Participants were selected based on their ability to provide a fresh tumor biopsy or an archival tumor tissue sample, and they must have at least one measurable lesion according to RECIST v1.1. The general health status of participants is assessed with an **Eastern Cooperative Oncology Group (ECOG) performance status** of 0 to 1 at screening. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection criteria.
Plans and Procedures
The clinical trial is designed as a **Phase 1/2**, first-in-human study to evaluate the safety, efficacy, and pharmacokinetics 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. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The estimated duration of the trial is from January 2024 to January 2028, with participant involvement expected to last until the end of the study or until early termination criteria are met.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, progression despite standard therapies, and the ability to provide a fresh tumor biopsy. The screening visit will also evaluate the Eastern Cooperative Oncology Group (ECOG) performance status. Following successful screening, participants will be enrolled in the study and will attend regular follow-up visits to monitor treatment response and safety. These visits will include assessments of the objective response rate (ORR) using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as well as evaluations of secondary endpoints such as duration of response, disease control rate, and overall survival.
The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to gather comprehensive data on the efficacy and safety of the treatment. Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. The trial aims to provide valuable insights into the potential benefits of **DCC-3116** in combination with other agents for treating various solid tumors, including **pancreatic ductal adenocarcinoma**, **colorectal cancer**, **melanoma**, **metastatic solid tumor**, **advanced solid tumor**, and **non-small cell lung cancer**.
Treatment
The clinical trial involves the administration of several experimental medications, each with specific characteristics. **LUMYKRAS** 120 mg film-coated tablets, containing the active substance **sotorasib**, are administered orally. The pharmaceutical form is a film-coated tablet, and the medication is produced by Amgen Europe B.V. The administration frequency and dosage schedule are determined based on the trial protocol, ensuring participant compliance through regular monitoring.
**Mektovi** 15 mg film-coated tablets, containing **binimetinib**, are also administered orally. This medication is manufactured by Pierre Fabre Medicament. The film-coated tablet form facilitates oral administration, and the dosing schedule is aligned with the trial's objectives, with compliance monitored throughout the study.
**Mekinist** is available in two dosages: 2 mg and 0.5 mg film-coated tablets, both containing the active substance **trametinib**. These tablets are produced by Novartis Europharm Limited and are administered orally. The trial protocol specifies the dosage and frequency, with adherence monitored to ensure accurate data collection.
**DCC-3116** is provided in a gastro-resistant tablet form, designed to withstand stomach acid and release the active substance in the intestine. This medication is produced by Deciphera Pharmaceuticals, LLC, and is administered orally. The trial protocol outlines the dosing schedule, and participant compliance is closely monitored to maintain the integrity of the study data.
All medications in this trial are chemically derived and are administered orally. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments. The study's main objective is to evaluate the objective response rate of combination therapy in patients with advanced or metastatic solid tumors with RAS/MAPK pathway mutations, using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Compliance with the dosing schedule is critical and is monitored throughout the trial to ensure the reliability of the results.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the **Objective Response Rate (ORR)**, which is defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. This primary efficacy endpoint will be evaluated during the Dose Expansion Phase (Part 2) of the trial based on Investigator Assessment.
Secondary efficacy endpoints will include the Duration of Response, Disease Control Rate at 16, 24, and 32 weeks, Time to Response, Progression-Free Survival, and Overall Survival, which is defined as the time from initiation of treatment until death. These parameters will provide a comprehensive evaluation of the treatment's efficacy over time.
Pharmacokinetic (PK) endpoints will also be assessed for DCC-3116 in combination with trametinib, binimetinib, and sotorasib. The PK parameters will include, but are not limited to, tmax, Cmax, Cmin, and AUC, providing insights into the drug's absorption, distribution, metabolism, and excretion when used in combination therapies.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female participant at least 18 years of age
- Have progressed despite standard therapies, or for whom conventional therapy is not considered effective or tolerable, as judged by the Investigator
- Must provide a fresh tumor biopsy from a primary or metastatic cancer lesion if it can be biopsied with acceptable risk as determined by the Investigator during the Screening Period
- Must have at least 1 measurable lesion according to RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) performance status at Screening of 0 to 1
Exclusion Criteria
- Must not have received the following within the specified time periods prior to the first dose of study drug: a. Prior therapies (anticancer or therapies given for other reasons) that are known strong or moderate inhibitors or inducers of CYP3A4 or P-gp (refer to Section 9.8.3) including certain herbal medications (eg, St. John’s Wort): 14 days or 5× the half-life of the medication (whichever is longer) b. 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) c. 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 d. Grapefruit or grapefruit juice: 14 days
- Has a prior or concurrent malignancy that requires treatment or is expected to require treatment for active cancer during this study. Hormonal maintenance after treatment is allowed
- Have not recovered from all toxicities from prior therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0 to Grade ≤1 or participant baseline prior to first dose of study drug (excluding alopecia). Participant baseline is defined as no change in severity grade within 28 days prior to signed informed consent
- Presence or history of central nervous system (CNS) metastases or leptomeningeal disease, with the following exceptions: • If there is a history of brain metastases, they must be stable for at least 6 months (no new metastases and no evidence of progression of known metastases at Screening compared to historical scans) • If there is a history of leptomeningeal disease, it must have cleared at least 6 months prior to Screening • If there are neurologic symptoms consistent with CNS disease, they must not be new or increasing in severity over at least 6 months prior to Screening • If there is a history of CNS metastasis or leptomeningeal disease, it must not require continued therapy
- 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
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 01 Sept 2025 | 18 |
 Germany | Not Recruiting | 01 Sept 2025 | 8 |
 Italy | Not Recruiting | 01 Sept 2025 | 30 |
 Spain | Not Recruiting | 01 Sept 2025 | 20 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
LUMYKRAS 120 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | — | — | PRD9412069 |
LUMYKRAS 240 mg film-coated tablets | Test | FILM-COATED TABLETS | ORAL | — | — | PRD11341702 |