IDE196 Combinations for Solid Tumors

Recruiting at 9 trial locations

Overseen By IDEAYA Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: IDEAYA Biosciences

Must not be taking: Statins, ALK inhibitors

Disqualifiers: Symptomatic brain metastases, AIDS, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

341 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IDE196 (also known as Darovasertib or LXS196), either alone or with other drugs, for individuals with specific solid tumors, such as certain types of melanoma and colorectal cancer. The goal is to determine if IDE196 is safe and effective in shrinking tumors with specific genetic mutations. The trial will evaluate the treatment's effectiveness and side effects to identify the best dose for future studies. Individuals with solid tumors featuring GNAQ or GNA11 mutations or PRKC fusions, who have experienced tumor growth after treatment, might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that treatment with prohibited medications that cannot be discontinued prior to study entry is an exclusion criterion. It would be best to discuss your current medications with the trial team to determine if any need to be stopped.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that IDE196 is under investigation for treating certain solid tumors, particularly those with GNAQ or GNA11 mutations. Early studies suggest that IDE196 alone is generally safe for patients, with manageable side effects.

When combined with crizotinib, early research also appears promising. The combination seems safe, as most participants did not experience severe side effects.

Similarly, studies of IDE196 with binimetinib indicate that this combination is well-tolerated, with no severe side effects reported.

These treatments remain in the testing phase. The trial is in its early stages, focusing on determining safe dosage levels to ensure the treatment can be safely administered to more people in future studies. Prospective participants can find reassurance in the positive initial safety results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for solid tumors, which often include chemotherapy or immunotherapy, IDE196 targets specific genetic mutations like GNAQ/11 and PRKC fusions found in certain tumors. Researchers are excited because IDE196 potentially offers a more personalized approach, aiming directly at the genetic drivers of the cancer. Moreover, when combined with other drugs like crizotinib or binimetinib, IDE196 may enhance treatment effectiveness by tackling multiple pathways that cancer cells use to grow. This combination strategy could lead to more robust responses and possibly improve outcomes for patients with these hard-to-treat tumors.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that IDE196, also known as darovasertib, may help treat certain solid tumors, such as metastatic uveal melanoma. This trial studies IDE196 in various treatment arms. Some participants will receive IDE196 alone, while others will receive it with crizotinib or binimetinib. Studies have found that IDE196 can shrink tumors in patients with specific genetic changes. When combined with crizotinib, IDE196 showed early positive results and proved generally safe for patients. Additionally, when paired with binimetinib, IDE196 led to better response rates and more tumor shrinkage compared to past data for similar conditions. These findings suggest that IDE196 could be effective for patients with tumors that have GNAQ/11 mutations or PRKC fusions. ^{1 3 5 6 7}

Who Is on the Research Team?

George Cole Jr., MD

Principal Investigator

[e-mail]

Are You a Good Fit for This Trial?

This trial is for adults with certain solid tumors, including metastatic uveal melanoma, skin cancer, and colorectal cancer that have specific genetic mutations or fusions. Participants must have had prior treatment with a MEK inhibitor (except for Binimetinib Combination), measurable disease, good performance status (ECOG ≤1), life expectancy over 3 months, adequate organ function and cardiac function (for Binimetinib Combination), and agree to use contraception. Exclusions include symptomatic brain metastases, pregnancy/breastfeeding women, recent thromboembolic events or surgeries.

Inclusion Criteria

I have a history of fainting.

My organs are working well.

I have spinal cord compression.

Exclusion Criteria

I have previously been treated with a MEK inhibitor.

I have a muscle disorder that increases my CPK levels.

I have a history of fainting.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Dose Escalation

Assessment of safety, tolerability, and pharmacokinetics of IDE196, alone and in combination with binimetinib or crizotinib, to determine the recommended Phase 2 dose

28 days per cycle

Phase 2 Dose Expansion

Evaluation of safety and anti-tumor activity of IDE196, alone and in combination with binimetinib or crizotinib, at the recommended Phase 2 dose

Approx. 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approx. 48 months

What Are the Treatments Tested in This Trial?

Interventions

• Binimetinib
• Crizotinib
• IDE196

Trial Overview The study tests the safety and effectiveness of IDE196 alone or in combination with Crizotinib or Binimetinib in patients whose tumors have GNAQ/11 mutations or PRKC fusions. It includes dose escalation to find the right amount of drug and then expands to more patients at this dose. The effects of food on IDE196's absorption are also studied.

How Is the Trial Designed?

Group I: PK Substudy with Pravastatin (OBTP1B1 Substrate) Experimental Treatment 1 Intervention

A PK substudy with approximately 18 patients will be nested within the IDE196 and crizotinib combination expansion cohort to evaluate the impact on the pravastatin PK profile by the steady state exposures of IDE196.

Group II: Dose Optimization Crizotinib Combination Experimental Treatment 2 Interventions

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle

Group III: Dose Expansion Monotherapy Experimental Treatment 1 Intervention

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)

Group IV: Dose Expansion Crizotinib Combination Experimental Treatment 2 Interventions

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors) Previously treated MUM, Treatment naïve MUM, MUM patients with human leukocyte antigen (HLA)-A\*02:01 positive status

Group V: Dose Expansion Binimetinib Combination Experimental Treatment 2 Interventions

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)

Group VI: Dose Escalation Monotherapy Experimental Treatment 1 Intervention

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

Group VII: Dose Escalation Crizotinib Combination Experimental Treatment 2 Interventions

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle

Group VIII: Dose Escalation Binimetinib Combination Experimental Treatment 2 Interventions

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle

Group IX: Crizotinib Monotherapy with Crossover to Combination Experimental Treatment 2 Interventions

Crizotinib dosed orally, twice daily (BID) for each 28-day cycle until disease progression then IDE196 added and dosed orally, twice daily (BID) for each 28-day cycle

Who Is Running the Clinical Trial?

IDEAYA Biosciences

Lead Sponsor

Trials

6

Recruited

1,300+

Published Research Related to This Trial

In a phase II trial involving 150 patients with metastatic castration-resistant prostate cancer (mCRPC), the addition of capivasertib to standard chemotherapy did not significantly prolong composite progression-free survival (cPFS) compared to placebo, with median cPFS of 7.03 months for capivasertib versus 6.70 months for placebo.

However, capivasertib was associated with a significant improvement in overall survival (OS), with a median OS of 31.15 months for the capivasertib group compared to 20.27 months for the placebo group, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID). Crabb, SJ., Griffiths, G., Marwood, E., et al.[2022]

In a phase 1 trial involving 30 pediatric patients with recurrent or refractory solid and CNS tumors, prexasertib was administered safely with no dose-limiting toxicities observed, establishing a recommended phase 2 dose of 150 mg/m2.

While the treatment did not result in objective responses, it did lead to stable disease in three patients, indicating some potential for disease control, particularly in specific tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of prexasertib (LY2606368), a CHK1/2 inhibitor, in pediatric patients with recurrent or refractory solid tumors, including CNS tumors: A report from the Children's Oncology Group Pediatric Early Phase Clinical Trials Network (ADVL1515). Cash, T., Fox, E., Liu, X., et al.[2022]

A high-throughput drug screen identified olaparib, a PARP inhibitor, as the most effective drug to combine with selinexor in ovarian cancer, showing significant antitumor effects in both in vitro and in vivo models.

The combination treatment resulted in lower tumor weights and fewer tumor nodules in mouse models, with mechanisms indicating reduced DNA damage repair protein expression and increased tumor suppressor protein expression, suggesting a promising strategy for enhancing the efficacy of PARP inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rational Combination of CRM1 Inhibitor Selinexor and Olaparib Shows Synergy in Ovarian Cancer Cell Lines and Mouse Models. Handley, KF., Rodriguez-Aguayo, C., Ma, S., et al.[2022]

In a study involving 20 children and young adults with recurrent/refractory cancers, the combination of the WEE1 inhibitor adavosertib and carboplatin showed significant hematologic toxicity, including prolonged neutropenia and thrombocytopenia, leading to dose adjustments.

Despite the toxicity, the treatment demonstrated some efficacy, with an overall response rate of 11%, particularly in patients with specific molecular alterations related to DNA repair and replication stress, suggesting potential biomarkers for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II study of the WEE1 inhibitor adavosertib (AZD1775) in combination with carboplatin in children with advanced malignancies: Arm C of the AcSé-ESMART trial. Gatz, SA., Harttrampf, AC., Brard, C., et al.[2023]

SGN-B6A is an antibody-drug conjugate specifically targeting integrin beta-6, which is overexpressed in various solid tumors and associated with poor prognosis, showing promising preclinical efficacy in models of non-small cell lung, pancreatic, pharyngeal, and bladder cancers.

In nonclinical studies, SGN-B6A was well-tolerated in cynomolgus monkeys at doses up to 6 mg/kg, with dose-limiting hematologic toxicities but no significant target-mediated toxicity, paving the way for a phase I clinical trial to assess its safety and effectiveness in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SGN-B6A: A New Vedotin Antibody-Drug Conjugate Directed to Integrin Beta-6 for Multiple Carcinoma Indications. Lyon, RP., Jonas, M., Frantz, C., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03947385

Study of IDE196 in Patients with Solid Tumors Harboring ... 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.

2. cancer.gov cancer.gov/clinicaltrials/NCI-2019-04523

Study of IDE196 in Patients with Solid Tumors Harboring ... 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 ...

3. ir.ideayabio.com ir.ideayabio.com/2019-11-20-Phase-1-2-Clinical-Trial-Data-for-IDE196-Presented-at-Society-for-Melanoma-Research-Congress

Phase 1/2 Clinical Trial Data for IDE196 Presented at ... This clinical trial is evaluating the tolerability and preliminary clinical activity of IDE196 for the treatment of Metastatic Uveal Melanoma ( ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10419210/

Darovasertib, a novel treatment for metastatic uveal ... Data suggests that darovasertib may be used to treat diseases other than melanoma and solid tumors. A recent in vitro study was conducted to ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT03947385

Study of IDE196 in Patients with Solid Tumors Harboring ... "The presentation will include data from over 40 patients in the trial, including the first reported median overall survival (OS) data for the combination of ...

6. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/phase-1-2-study-ide196-patients-solid-tumors-harboring-gnaq-11-mutations-or-prkc-fusions

A Phase 1/2 study of IDE196 in patients with solid tumors ... The purpose of this study is to evaluate the safety profile of IDE196 (an “investigational” drug), in enrolled subjects to find out if it is safe and ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03947385/

Clinical Trial: NCT03947385 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.