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

• Sponsor: Kinnate Biopharma (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04913285
• Collaborator: (none)
• Enrollment: 155
• Locations: 18
• Arms: 3
• Anticipated Duration (Months): 33.9
• Patients Per Site: 8.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor, Adult; Non-small Cell Lung Cancer; Melanoma	Drug: KIN-2787; Drug: KIN-2787 and binimetinib	Phase 1

Detailed 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 II or III mutations, including lung cancer, melanoma, and other selected solid tumors.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 155 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/1b Open-label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of KIN-2787 in Participants With BRAF and/or NRAS Mutation-positive Solid Tumors.
• Actual Study Start Date: Aug 4, 2021
• Anticipated Primary Completion Date: Mar 1, 2024
• Anticipated Study Completion Date: Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation Monotherapy (Part A1) Dose escalation of KIN-2787	Drug: KIN-2787; KIN-2787 will be administered orally twice daily in 28-day cycles
Experimental: Dose Escalation Combination therapy (Part A2) Dose escalation of KIN-2787 and binimetinib	Drug: KIN-2787 and binimetinib; KIN-2787 and binimetinib will be administered orally twice daily in 28-day cycles
Experimental: Dose Expansion (Part B) Dose expansion evaluating the recommended phase 2 dose (RP2D) of KIN-2787	Drug: KIN-2787; KIN-2787 will be administered orally twice daily in 28-day cycles

Outcome Measures

Primary Outcome Measures

1. Part A1 Dose escalation monotherapy: [Initiation of study drug through 28 days after last dose (up to approximately 18 months)]

   To determine the safety and tolerability of oral administration of KIN-2787 including dose-limiting toxicities (DLTs), and to identify the maximum tolerated dose (MTD) and/or the appropriate dose for further clinical investigation in Part B Dose Expansion.

2. Part A2 Dose Escalation: KIN-2787 + Binimetinib Combination [Initiation of study drug through 28 days after last dose (up to approximately 18 months)]

   To determine the safety and tolerability of oral administration of KIN-2787 + binimetinib including DLTs, and to identify the MTD and/or the appropriate dose for further clinical investigation.

3. In Part B (Dose Expansion) - objective response rate (ORR) using RECIST v1.1. [Initiation of study drug until disease progression (up to approximately 36 months)]

   To assess preliminary evidence of the anti-cancer activity of KIN-2787

4. In Part B (Dose Expansion) - disease control rate (DCR). [Initiation of study drug until disease progression (up to approximately 36 months)]

5. In Part B (Dose Expansion) - duration of overall response (DOR). [Initiation of study drug until disease progression (up to approximately 36 months)]

   Measure of clinical benefit, defined as the time from initial tumor response to documented tumor progression

6. In Part B (Dose Expansion) - duration of stable disease. [Initiation of study drug until disease progression (up to approximately 36 months)]

Secondary Outcome Measures

1. Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to tmax. [Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)]

2. Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to AUC. [Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)]

3. Part A1 Dose Escalation: Characterization of PK properties and effect of food on PK of KIN-2787 including, but not limited to Cmax. [Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)]

4. Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to Cmax. [Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)]

5. Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to AUC. [Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)]

6. Part A2 Dose Escalation: characterization of PK properties of KIN-2787 and binimetinib in combination including, but not limited to tmax. [Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)]

7. Part B Dose Expansion: characterization of PK properties of KIN-2787 including, but not limited to AUC. [Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)]

8. Part B Dose Expansion: characterization of PK properties of KIN-2787 including, but not limited to Cmax. [Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)]

9. Part B Dose Expansion: characterization of PK properties of KIN-2787 including, but not limited to tmax. [Initiation of study drug through Cycle 5, where each cycle is 28 days (up to approximately 4 months)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 or evaluable disease by RECIST v1.1.

• ECOG performance status 0, 1, or 2.

• Adequate organ function, as measured by laboratory values (criteria listed in protocol).

• Able to swallow, retain, and absorb oral medications.

Exclusion Criteria:

• Known clinically-active or clinically-progressive brain metastases from non-brain tumors.

• 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.

• In Part B Dose Expansion, patients with BRAF Class I mutations are excluded.

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	UCSD Moores Cancer Center	La Jolla	California	United States	92093
3	University of Southern California	Los Angeles	California	United States	90033
4	UCLA	Los Angeles	California	United States	90095
5	Stanford Cancer Center	Stanford	California	United States	94305
6	Sarah Cannon Research Institute - Lake Nona	Orlando	Florida	United States	32827
7	Moffitt Cancer Ceter	Tampa	Florida	United States	33612
8	Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
9	NYU Langone	New York	New York	United States	10016
10	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
11	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
12	Linear Clinical Research	Perth	Western Australia	Australia	6009
13	Institut Bergonie	Bordeaux		France
14	Centre Leon Berard	Lyon		France
15	CHU Nantes-Hotel Dieu	Nantes		France
16	Hospital Quiron Dexeus	Barcelona		Spain
17	Hospital Universitario Insular de Gran Canaria	Las Palmas De Gran Canaria		Spain
18	INCLIVA (Hospital Clinico de Valencia)	Valencia		Spain

Sponsors and Collaborators

• Kinnate Biopharma

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kinnate Biopharma
• ClinicalTrials.gov Identifier: NCT04913285
• Other Study ID Numbers: KN-8701
• First Posted: Jun 4, 2021
• Last Update Posted: Aug 5, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Kinnate Biopharma: BRAF inhibitor; BRAF; pan-RAF; pan-RAF inhibitor; RAF1; ARAF; BRAF alteration; BRAF Class II; BRAF Class III; V600; tumor growth inhibitor (TGI); melanoma; NSCLC; solid tumor; targeted therapy; BRAF Class I; NRAS; Metastatic; Unresectable; CRC; ATC; Colon; Thyroid; Advanced
• Additional relevant MeSH terms: Melanoma

Study Results

No Results Posted as of Aug 5, 2022