What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies like KRAS G12C inhibitors (e.g., Adagrasib) and PARP inhibitors (e.g., Olaparib). The known side effects of KRAS G12C inhibitors often include gastrointestinal issues such as nausea and diarrhea, as well as fatigue and liver enzyme abnormalities. PARP inhibitors are associated with side effects like nausea, fatigue, vomiting, anemia, and increased risk of infections. Both types of treatments can also cause more serious adverse effects, which should be monitored by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of Non-Small Cell Lung Cancer (NSCLC). For KRAS G12C mutations, sotorasib has been approved as a targeted therapy. Adagrasib, another KRAS G12C inhibitor, is currently under investigation. For patients with NSCLC harboring BRCA mutations or other homologous recombination repair (HRR) deficiencies, PARP inhibitors like Olaparib have shown efficacy in clinical trials. These treatments represent a shift towards personalized, genotype-directed therapy in NSCLC, aiming to improve outcomes by targeting specific genetic alterations.

What other types of research exist?

Promising novel alternatives for KRAS G12C mutated NSCLC include the MEK inhibitor selumetinib, which has shown increased median overall survival and improved progression-free survival when combined with docetaxel. Additionally, immunotherapy options such as pembrolizumab combined with chemotherapy have shown efficacy in NSCLC patients without specific driver mutations.

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KRAS G12C Inhibitor

Adagrasib + Olaparib for Solid Tumors

Phase 1

Recruiting

Led By Timothy Yap, MD

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Women and men, who are sexually active and of childbearing potential, must agree to use two highly effective forms of contraception prior to study entry, for the duration of study participation, and for 6 months following termination of the study treatment

Histologically confirmed diagnosis of a solid tumor malignancy with a KRAS G12C mutation

Must not have

Participants with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML

Concomitant use of known strong or moderate CYP3A inducers

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of two drugs, adagrasib and olaparib, in patients with advanced solid tumors that have specific genetic mutations. The goal is to find a safe dose and see if the combination can effectively block cancer growth and prevent cancer cells from repairing themselves. Olaparib has shown activity in various cancers, particularly those with certain genetic mutations.

Who is the study for?

Adults with advanced solid tumors that have specific mutations (KRAS G12C or KEAP1) can join this trial. They should be in good physical condition, not have major health issues that could affect the study, and agree to use effective contraception. People with certain gastrointestinal conditions, uncontrolled infections, recent significant bleeding or surgery, or those on strong CYP3A inhibitors/inducers are excluded.

What is being tested?

The trial is testing a combination of two drugs: Adagrasib and Olaparib for patients with certain genetic mutations in their tumors. The goal is to find the safest dose level. Participants will receive both medications and be monitored for how well they tolerate them and any signs of tumor response.

What are the potential side effects?

Possible side effects include nausea, fatigue, blood count changes leading to increased infection risk or bruising, shortness of breath, allergic reactions to medication components, liver function changes which may cause yellowing skin or eyesight problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I agree to use two effective birth control methods during and 6 months after the study.

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My cancer has a specific KRAS G12C mutation.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

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I am not taking any strong or moderate drugs that affect liver enzymes.

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

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I do not have severe heart, seizure, spinal, lung, or major blood vessel conditions.

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I have had a bone marrow or cord blood transplant.

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I have a history of HIV or Hepatitis B/C.

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I am not taking strong or moderate CYP3A inhibitors.

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I have cancer cells in the fluid around my brain and spinal cord.

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I have heart problems.

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I have recovered from side effects of previous cancer treatments, except for hair loss.

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I have active cancer spread to my brain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Adagrasib+OlaparibExperimental Treatment2 Interventions

Participants will take adagrasib and olaparib by mouth 2 times each day. Each dose should be taken at about 12 hours apart (1 dose in the morning, 1 dose in the evening). The study drugs should be swallowed whole with water. Do not chew, crush, dissolve, or divide the study drugs. If forget a dose and less than 2 hours have passed since the usual time participants take the study drug, take the dose as soon as participants remember. If more than 2 hours have passed, do not take the dose. Wait and take the next dose as scheduled

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Adagrasib

2023

Completed Phase 1

~20

Olaparib

2007

Completed Phase 4

~2190

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) often involve targeted therapies that focus on specific genetic mutations within the cancer cells. Adagrasib, a KRAS G12C inhibitor, works by specifically targeting and inhibiting the KRAS G12C mutation, which is a common driver of cancer cell growth in NSCLC. This inhibition prevents the cancer cells from proliferating. Olaparib, a PARP inhibitor, impedes the cancer cells' ability to repair DNA damage, leading to cell death, particularly in cells with existing DNA repair deficiencies. These targeted treatments are crucial for NSCLC patients as they offer a more personalized approach, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Tailoring tyrosine kinase inhibitors to fit the lung cancer genome.