A Phase 1/2 Study of DCC-3116 in Patients With MAPK Pathway Mutant Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Deciphera Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 30 Mar 2026

Decision date (initial)

2024-01-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Deciphera Pharmaceuticals, LLC

External identifiers

EU CT number

2022-501474-19-00

ClinicalTrials.gov

NCT04892017

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Dose response, Pharmacodynamic, Pharmacokinetic

The main objective of Part 2 is to evaluate the objective response rate (ORR) of combination therapy at the RP2D the Expansion Cohort(s) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary objectives 3

1. To further characterize the efficacy of DCC-3116 at the RP2D in combination with sotorasib in the expansion cohort(s)
2. To further characterize the PK of DCC-3116 and sotorasib when administered in combination
3. To evaluate the safety and tolerability of DCC-3116 in combination with sotorasib

Conditions and MedDRA coding

Non-Small Cell Lung Cancer

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female participant at least 18 years of age
2. Have progressed despite standard therapies, or for whom conventional therapy is not considered effective or tolerable, as judged by the Investigator
3. 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
4. Must have at least 1 measurable lesion according to RECIST v1.1
5. Eastern Cooperative Oncology Group (ECOG) performance status at Screening of 0 to 1

Exclusion criteria 6

1. 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
2. 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
3. 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
4. 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
5. 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
6. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint in the Dose Expansion Phase (Part 2) will be the Objective Response Rate (ORR) based on Investigator Assessment, defined as the proportion of participants who achieve confirmed complete response (CR) or partial response (PR) per RECIST v1.1.

Secondary endpoints 3

1. Efficacy: The following endpoints assessing efficacy of DCC-3116 will be evaluated: • Duration of Response • Disease Control Rate at 16, 24, and 32 weeks • Time to response • Progression-free-survival • Overall survival (defined as the time from initiation of treatment until death)
2. Pharmacokinetics (PK): PK endpoints will be evaluated for DCC-3116 and sotorasib when administered in combination. These PK parameters will include, but not be limited to: • tmax • Cmax • Cmin • AUC
3. Safety: Safety endpoints that will be evaluated include the following: • Treatment-emergent adverse event • Serious adverse events • Dose reduction, interruption, or discontinuation of study drugs due to toxicity

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Deciphera Pharmaceuticals Inc.

Sponsor organisation

Deciphera Pharmaceuticals Inc.

Address

200 Smith Street

City

Waltham

Postcode

02451-0099

Country

United States

Scientific contact point

Organisation

Deciphera Pharmaceuticals LLC

Contact name

Clinical trial information

Public contact point

Organisation

Deciphera Pharmaceuticals LLC

Contact name

Clinical trial information

Third parties 17

Locations

4 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 44 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications