2900 Participants Needed

Targeted Therapy for Solid Tumors

Recruiting at 477 trial locations
Age: Any Age
Sex: Any
Trial Phase: Phase 2
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is binimetinib safe for humans?

Binimetinib has been studied in various clinical trials and has shown an acceptable safety profile in patients with certain types of cancer, such as melanoma and non-small-cell lung cancer. It has been tested alone and in combination with other drugs, and the studies have helped determine safe dosage levels for humans.12345

What makes the drug combination of Binimetinib, Fulvestrant, Ipatasertib, Leucovorin, Nilotinib, Olaparib, Palbociclib, Selumetinib, and Sotorasib unique for treating solid tumors?

This drug combination is unique because it targets specific genetic and immunological changes in solid tumors, potentially improving survival by using multiple agents that affect different pathways. This approach is part of a new wave of targeted therapies that aim to personalize treatment based on the tumor's characteristics, offering hope for better outcomes in cancers that have limited treatment options.678910

What data supports the effectiveness of the drug Binimetinib for treating solid tumors?

Research shows that Binimetinib, when used with other drugs, has shown effectiveness in treating advanced solid tumors, especially in cases with specific genetic mutations like BRAF and NRAS in melanoma. It has also been studied in combination with other treatments for colorectal cancer and non-small cell lung cancer, showing potential benefits.1341011

Who Is on the Research Team?

JM

James M Ford

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have spread and are not responding to standard treatments or lack treatment options proven to extend life. Participants need available tumor tissue samples, must be in fair health (ECOG 0-2), and willing to undergo genetic testing of their tumors. It's not suitable for those who've had a good response to recent therapies.

Inclusion Criteria

My condition worsened after at least one standard treatment.
I am mostly active and can care for myself.
You need to have samples of your tumor preserved in a specific way.
See 14 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Registration

Patients undergo tumor mutational screening of previously-collected tumor samples for specific, pre-defined mutations, amplifications, or translocations of interest via tumor sequencing.

2-4 weeks
1 visit (in-person)

Treatment

Patients with mutations targeted to investigational combination therapies are assigned to 1 of 20 treatment subprotocols. Treatment includes various drug administrations and monitoring procedures.

28 days per cycle, up to 5 years
Multiple visits per cycle (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up includes CT or MRI scans and blood sample collections.

Up to 3 years
Every 3 months for 2 years, then every 6 months for 1 year

What Are the Treatments Tested in This Trial?

Interventions

  • Binimetinib
  • Biopsy
  • Biospecimen Collection
  • Bone Marrow Aspiration
  • Bone Scan
  • Computed Tomography
  • Echocardiography
  • Fluorouracil
  • Fulvestrant
  • Ipatasertib
  • Leucovorin
  • Magnetic Resonance Imaging
  • Multigated Acquisition Scan
  • Mutation Carrier Screening
  • Nilotinib Hydrochloride Monohydrate
  • Olaparib
  • Oxaliplatin
  • Paclitaxel
  • Palbociclib
  • Positron Emission Tomography
  • Selumetinib Sulfate
  • Sotorasib
Trial Overview The ComboMATCH trial tests targeted therapies based on genetic mutations in patients' tumors. Various drugs like Oxaliplatin, Ipatasertib, and Olaparib are matched with specific genetic changes identified through testing. The study aims to control the tumor growth by personalizing treatment plans.
How Is the Trial Designed?
20Treatment groups
Experimental Treatment
Active Control
Group I: EAY191-S3 (activating AKT mutation)Experimental Treatment6 Interventions
Group II: EAY191-N5 Arm II (neratinib maleate,palbociclib)Experimental Treatment8 Interventions
Group III: EAY191-N4 Arm I (RAS pathway mutations)Experimental Treatment9 Interventions
Group IV: EAY191-N2 Cohort II (NF1 mutations)Experimental Treatment9 Interventions
Group V: EAY191-N2 Cohort I (Arm II) (NF1 mutations)Experimental Treatment8 Interventions
Group VI: EAY191-N2 Cohort I (Arm I) (NF1 mutations)Experimental Treatment9 Interventions
Group VII: EAY191-E5 Cohort II (sotorasib)Experimental Treatment6 Interventions
Group VIII: EAY191-E5 Cohort I Arm A (sotorasib, panitumumab)Experimental Treatment6 Interventions
Group IX: EAY191-E4 (taxane therapy)Experimental Treatment6 Interventions
Group X: EAY191-A6 Arm II (RAS/RAF/MEK/ERK mutations)Experimental Treatment11 Interventions
Group XI: EAY191-A6 Arm I (RAS/RAF/MEK/ERK mutations)Experimental Treatment11 Interventions
Group XII: EAY191-A3 Monotherapy Cohort 1 (binimetinib)Experimental Treatment6 Interventions
Group XIII: EAY191-A3 Combo Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)Experimental Treatment6 Interventions
Group XIV: EAY191-A2 (Cohort 3, Arm D)Experimental Treatment7 Interventions
Group XV: EAY191-A2 (Cohort 2, Arm C)Experimental Treatment7 Interventions
Group XVI: EAY191-A2 (Cohort 2, Arm B)Experimental Treatment8 Interventions
Group XVII: EAY191-A2 (Cohort 1, Arm A)Experimental Treatment8 Interventions
Group XVIII: EAY191-N5 Arm I (neratinib maleate)Active Control7 Interventions
Group XIX: EAY191-E5 Cohort I Arm B (sotorasib)Active Control5 Interventions
Group XX: EAY191-N4 Arm II (RAS pathway mutations)Active Control8 Interventions

Binimetinib is already approved in United States, European Union, Canada, Japan for the following indications:

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Approved in United States as Mektovi for:
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Approved in European Union as Mektovi for:
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Approved in Canada as Mektovi for:
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Approved in Japan as Mektovi for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

Binimetinib, an uncompetitive inhibitor of MEK1/2, has shown significant efficacy in treating metastatic melanoma, particularly in combination with encorafenib, resulting in a progression-free survival (PFS) of 14.9 months compared to 7.3 months with vemurafenib alone in Phase 3 trials.
While binimetinib has a tolerable safety profile, there is currently no long-term data on durable responses or overall survival benefits compared to other treatments, highlighting the need for individualized treatment plans for patients with BRAF-mutated metastatic melanoma.
The discovery and development of binimetinib for the treatment of melanoma.Tran, B., Cohen, MS.[2021]
In a phase 1 study involving 93 patients with advanced solid tumors, binimetinib was found to have a maximum tolerated dose (MTD) of 60 mg twice daily, but the recommended dose for further studies was adjusted to 45 mg due to ocular toxicity.
Binimetinib showed a manageable safety profile with common side effects including rash and nausea, and demonstrated preliminary anti-tumor activity with three patients with biliary cancer achieving objective responses, indicating potential for further investigation in this group.
A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor.Bendell, JC., Javle, M., Bekaii-Saab, TS., et al.[2022]
In a phase Ib study involving 89 patients with advanced solid tumors, the combination of binimetinib (a MEK inhibitor) and buparlisib (a PI3K inhibitor) showed some efficacy, particularly in RAS/BRAF-mutant ovarian cancer, where 12% of patients achieved a partial response.
However, the treatment was associated with significant toxicities, leading to a lower than expected dose intensity, suggesting that alternative dosing strategies, like pulsatile dosing, may be necessary to improve safety and tolerability in future trials.
Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations.Bardia, A., Gounder, M., Rodon, J., et al.[2023]

Citations

The discovery and development of binimetinib for the treatment of melanoma. [2021]
A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. [2022]
Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations. [2023]
A phase I clinical trial of binimetinib in combination with FOLFOX in patients with advanced metastatic colorectal cancer who failed prior standard therapy. [2022]
A phase I study of binimetinib (MEK 162), a MEK inhibitor, plus carboplatin and pemetrexed chemotherapy in non-squamous non-small cell lung cancer. [2021]
Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. [2023]
Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. [2023]
Response and safety of sunitinib in a heavily pre-treated metastatic non-small cell lung carcinoma patient. [2018]
[Pharmacotherapy of solid tumors. New hopes and frustrations]. [2021]
Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC). [2022]
A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours. [2021]
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