Adagrasib + Palbociclib for Solid Tumors

No longer recruiting at 11 trial locations

Overseen By Mirati Therapeutics Study Locator Services

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mirati Therapeutics Inc.

Disqualifiers: Other active cancer, Cardiac abnormalities, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two drugs, MRTX849 (adagrasib) and palbociclib, to determine their safety and effectiveness when combined to treat advanced solid tumors with the KRAS G12C mutation. The researchers aim to establish the maximum safe dosage and assess whether the combination can combat these tumors. The study seeks participants with a solid tumor featuring the KRAS G12C mutation that is either inoperable or has metastasized. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the chance to be among the first to receive this potentially groundbreaking therapy.

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

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

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

Research shows that adagrasib, when used alone, has promising results in treating certain tumors with the KRAS G12C mutation. It is generally well-tolerated, meaning most people can manage the side effects. Ongoing research aims to understand the safety of using adagrasib with palbociclib, a drug often used to treat breast cancer.

Previous studies have examined the safety of this combination and how the body processes these drugs. As this trial is in an early stage, its goal is to determine the safest dose and monitor for side effects. Participants might experience some side effects, but these are closely monitored to ensure safety.

Overall, the combination of adagrasib and palbociclib is being tested for safety and potential benefits in treating certain cancers. The research remains in the early stages, with a focus on carefully studying the safety of this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Adagrasib combined with Palbociclib for solid tumors because these drugs target cancer in a novel way compared to standard treatments. Adagrasib (MRTX849) specifically targets the KRAS G12C mutation, a common driver in many cancers, offering a tailored approach where traditional chemotherapy might not. Palbociclib, on the other hand, inhibits CDK4/6, which helps control cell division, potentially enhancing the effectiveness of Adagrasib. Together, this combination aims to attack cancer cells more precisely while minimizing damage to healthy cells, which could lead to better outcomes with fewer side effects.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors with KRAS G12C mutation?

This trial will study the combination of adagrasib and palbociclib for treating solid tumors. Research has shown that adagrasib may help treat solid tumors with a specific change in the KRAS gene, known as the KRAS G12C mutation, which can cause cancer to grow. When combined with palbociclib, a drug that stops cancer cells from dividing, the treatment aims to block tumor growth more effectively. Early lab studies suggest that this combination might better prevent cancer from worsening. Initial research showed that this combo can shrink tumors, offering potential benefits for patients with this mutation. While more research is needed, the early results are promising for those with advanced solid tumors. ^{2 3 6 7 8}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have a specific mutation called KRAS G12C. Participants must not have any curative treatment options available and should have adequate organ function. They can't join if they have another active cancer, had severe side effects from similar treatments before, or conditions affecting drug absorption.

Inclusion Criteria

My cancer cannot be removed by surgery or has spread.

My cancer has a specific KRAS G12C mutation.

There are no treatments that can cure my condition.

Exclusion Criteria

I do not have any other active cancer.

I have heart problems.

I have a history of serious gut issues that could affect medication absorption.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation of MRTX849 and palbociclib to determine maximum tolerated dose in combination

24 months

Dose Expansion

Expansion cohorts to ensure sufficient safety experience, pharmacokinetic data, and early evidence of clinical activity

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MRTX849
• Palbociclib

Trial Overview The study tests the combination of two drugs: Adagrasib (MRTX849) and Palbociclib on patients with advanced solid tumors harboring the KRAS G12C mutation to assess safety and effectiveness.

How Is the Trial Designed?

Group I: Dose Expansion Experimental Treatment 2 Interventions

Expansion cohorts may be implemented to ensure sufficient safety experience, pharmacokinetic data and early evidence of clinical activity of MRTX in combination with palbociclib.

Group II: Dose Escalation Experimental Treatment 2 Interventions

Dose escalation of MRTX849 and palbociclib to determine maximum tolerated dose in combination.

MRTX849 is already approved in United States, European Union for the following indications:

Approved in United States as Krazati for:

• Locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutations
• Locally advanced or metastatic colorectal cancer with KRAS G12C mutations

Approved in European Union as Krazati for:

• Non-small cell lung cancer with KRAS G12C mutations

Who Is Running the Clinical Trial?

Mirati Therapeutics Inc.

Lead Sponsor

Trials

73

Recruited

8,900+

Dr. Charles M. Baum

Mirati Therapeutics Inc.

Chief Executive Officer since 2023

MD, PhD

Dr. Joseph Leveque

Mirati Therapeutics Inc.

Chief Medical Officer since 2021

MD

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/CT242/702743/Abstract-CT242-KRYSTAL-16-A-phase-I-Ib-trial-of

Abstract CT242: KRYSTAL-16: A phase I/Ib trial of adagrasib ... A multicenter phase I/Ib trial evaluating the safety, PK, pharmacodynamics, and preliminary clinical activity of adagrasib in combination with palbociclib.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12323406/

Adagrasib in the treatment of colorectal cancer - PMC When adagrasib is combined with cetuximab, a drug that blocks a protein called EGFR, the results were improved even more – the tumors shrank for ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03785249

NCT03785249 | Phase 1/2 Study of MRTX849 in Patients ... This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid ...

4. researchgate.net researchgate.net/publication/361338226_Abstract_CT242_KRYSTAL-16_A_phase_IIb_trial_of_adagrasib_MRTX849_in_combination_with_palbociclib_in_patients_with_advanced_solid_tumors_with_KRASG12C_mutation

KRYSTAL-16: A phase I/Ib trial of adagrasib (MRTX849) in ... Palbociclib, a CDK4/6 inhibitor, disrupts cancer cell proliferation by inducing cell cycle arrest by preventing the G1 to S phase transition. Preclinical data ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-00869

Adagrasib in Combination With Palbociclib in Patients ... This study will evaluate the safety and clinical activity of MRTX849 (adagrasib) in combination with palbociclib in patients with advanced solid tumor ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05178888?term=AREA%5BExpandedAccessNCTId%5DNCT05162443&rank=3

Adagrasib in Combination With Palbociclib in Patients ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

7. app.emergingmed.com app.emergingmed.com/emed/trial/315310

Adagrasib in Combination With Palbociclib in Patients ... This study will evaluate the pharmacokinetics and preliminary clinical activity of MRTX849 (adagrasib) in combination with palbociclib in patients with advanced ...

8. ctv.veeva.com ctv.veeva.com/study/adagrasib-in-combination-with-palbociclib-in-patients-with-advanced-solid-tumors-krystal16

Adagrasib in Combination With Palbociclib in Patients With ... This study will evaluate the safety and clinical activity of MRTX849 (adagrasib) in combination with palbociclib in patients with advanced solid ...