A Study to Evaluate KIN-2787 in Participants With BRAF and/or NRAS Mutation Positive Solid Tumors

Pierre Fabre

Status and phase: Enrolling; Phase 1

Conditions: Melanoma; Solid Tumor, Adult; Non-small Cell Lung Cancer

Treatments: Drug: KIN-2787 and binimetinib; Drug: KIN-2787

Study type: Interventional

Funder types: Industry

Identifiers

NCT04913285

KIN 2787CI101 (Other Identifier)

KN-8701

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of KIN-2787 in adults with BRAF/NRAS-mutated advanced or metastatic solid tumors.

Full description

This is a two-part, open-label, multi-center, dose escalation and dose expansion study in participants with BRAF mutation-positive and/or NRAS mutation-positive tumors designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of KIN-2787, a RAF small molecule kinase inhibitor, to determine a recommended Phase 2 dose (RP2D) of KIN-2787, and to assess the objective response to KIN-2787 therapy alone and in combination with binimetinib, a mitogen-activated protein kinase (MEK) inhibitor.

The dose expansion phase (Part B) will assess the safety and efficacy of KIN-2787 at the recommended dose and schedule in patients with cancers that contain BRAF Class I, II or III mutations, including lung cancer, melanoma, and other selected solid tumors.

Enrollment: 400 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Provide written informed consent prior to initiation of any study-specific procedures.
• Metastatic or advanced stage solid tumor
• Known BRAF Class I, Class II, or Class III alteration or melanoma with an NRAS mutation as confirmed by previous genomic analysis of tumor tissue or ctDNA.
• Measurable (Part A and B) or evaluable (Part A only) disease by RECIST v1.1.
• ECOG performance status 0-1
• Adequate organ function, as measured by laboratory values (criteria listed in protocol).
• Able to swallow, retain, and absorb oral medications.

Exclusion criteria

• Known participants who have received local therapy with either surgery and/or radiation therapy (participants with asymptomatic untreated brain metastasis may be eligible if met with certain criteria)
• In Part B Dose Expansion, previous treatment with any approved or in-development small molecule BRAF-, MEK-, or MAPK-directed inhibitor therapy.
• GI tract disease causing an inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, or uncontrolled inflammatory GI disease.
• Active, uncontrolled bacterial, fungal, or viral infection.
• Participant with a positive test result for SARS-CoV2 infection, is known to have asymptomatic infection or is suspected of having SARS-CoV2, is excluded
• Women who are lactating or breastfeeding, or pregnant.
• Participants with any other active treated malignancy within 3 years prior to enrollment

Complete inclusion and exclusion criteria are listed in the clinical study protocol.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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400 participants in 4 patient groups

Dose Escalation Monotherapy (Part A1)

Experimental group

Description:

Dose escalation of KIN-2787

Treatment:

Drug: KIN-2787

Dose Escalation Combination therapy (Part A2)

Experimental group

Description:

Dose escalation of KIN-2787 and binimetinib

Treatment:

Drug: KIN-2787 and binimetinib

Dose Expansion Monotherapy (Part B1)

Experimental group

Description:

Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787

Treatment:

Drug: KIN-2787

Dose Escalation Combination therapy (Part B2)

Experimental group

Description:

Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787 and binimetinib

Treatment:

Drug: KIN-2787 and binimetinib