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Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions

ConditionsMetastatic Uveal MelanomaCutaneous MelanomaColorectal CancerOther Solid Tumors
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorIDEAYA Biosciences

About this trial

This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid tumors.

Phase 1 (dose escalation - monotherapy) will assess safety, tolerability and pharmacokinetics of IDE196 via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.

Phase 1 (dose escalation - binimetib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and binimetinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.

Phase 1 (dose escalation - crizotinib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and crizotinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Evaluation of safety and efficacy across multiple doses may be explored in the dose optimization part of the study.

Crizotinib monotherapy with crossover to combination cohort may be assessed for safety and to show the contribution of each study drug to anti-tumor activity.

As of Protocol Amendment 10, Phase 1, Phase 2 dose expansion in IDE196 monotherapy, and Phase 2 dose expansion of IDE196 in combination with binimetinib have been fully enrolled. There were no patients enrolled in the crizotinib monotherapy cohorts.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patient must be ≥18 years of age and able to provide written informed consent

Measurable disease per RECIST v1.1

Eastern Cooperative Oncology Group ≤1 and expected life expectancy of > 3 months

Adequate organ function at screening

Disqualifiers

Previous treatment with a PKC inhibitor

Known MSI-H/dMMR tumors who have not previously received immune checkpoint inhibitors

Known symptomatic brain metastases

Adverse events from prior anti-cancer therapy that have not resolved

Trial design

Design model

Sequential

Treatments tested in this trial

  • IDE196

    Drug

    IDE196 dosed orally, twice daily for each 28-day cycle

  • Binimetinib

    Drug

    Binimetinib dosed orally, twice daily for each 28-day cycle

  • Crizotinib

    Drug

    Crizotinib dosed orally, twice daily for each 28-day cycle

Treatment groups

336 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: Dose Escalation Monotherapy (Enrollment Complete)Experimental treatment 1 intervention
Group B: Dose Expansion Monotherapy (Enrollment Complete)Experimental treatment 1 intervention
Group C: Dose Escalation Binimetinib Combination (Enrollment Complete)Experimental treatment 2 interventions
Group D: Dose Expansion Binimetinib Combination (Enrollment Complete)Experimental treatment 2 interventions
Group E: Dose Escalation Crizotinib Combination (Enrollment Complete)Experimental treatment 2 interventions
Group F: Dose Expansion Crizotinib Combination (Enrolling)Experimental treatment 2 interventions
Group G: Dose Optimization Crizotinib Combination (Enrollment Complete)Experimental treatment 2 interventions
Group H: Crizotinib Monotherapy with Crossover to Combination (Enrollment Complete)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Dose-limiting Toxicity (DLT)

Determine DLT of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

Time frame
28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
2

Incidence of Adverse Events

Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

Time frame
Approx. 8 months
3

Maximum Tolerated Dose (MTD)

Determine MTD of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

Time frame
28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
4

Recommended Phase 2 Dose (RP2D) as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

Determine RP2D of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

Time frame
Approx. 6 months

Secondary outcomes

1

Progression Free Survival (PFS) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment

RECIST v1.1

Time frame
Approx. 18 months
2

Overall Response Rate (ORR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts and by prior treatment status (pretreated or treatment naive) by Investigator response assessment

Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria

Time frame
Approx. 18 months
3

Duration of Response (DOR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by prior treatment status (pretreated or treatment naive) by Investigator response assessment

RECIST v1.1

Time frame
Approx. 18 months
4

Disease Control Rate (DCR) by Investigator

RECIST v1.1

Time frame
Approx. 18 months

Other outcomes

1

Overall Survival

From date of First Dose to End of Follow-up

Time frame
Approx. 18 months
2

Anti-tumor activity (ORR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Blinded Independent Review Committee (BICR)

RECIST v1.1

Time frame
Approx. 18 months
3

Anti-tumor activity (DOR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Blinded Independent Review Committee (BICR)

RECIST v1.1

Time frame
Approx. 18 months
4

Anti-tumor activity (PFS) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Blinded Independent Review Committee (BICR)

RECIST v1.1

Time frame
Approx. 18 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

IDEAYA Biosciences

Lead sponsor

Source ClinicalTrials.gov
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