INCB099280 + Adagrasib for Solid Tumors

No longer recruiting at 48 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Incyte Corporation

Must not be taking: Probiotics, Systemic antibiotics

Disqualifiers: Active malignancy, CNS metastases, Autoimmune, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments, INCB099280 (an experimental treatment) and adagrasib (a targeted therapy), to determine their safety and tolerability in people with certain advanced solid tumors. It focuses on patients whose cancer has a specific genetic change called KRASG12C. The trial consists of two parts: one to find the right dose and another to test it on specific cancers like non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). People previously treated for these cancers but still have the disease may be suitable candidates for this trial. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain conditions like active infections requiring treatment or recent use of systemic antibiotics may affect eligibility. It's best to discuss your specific medications with the trial team.

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

Research has shown that adagrasib, a drug targeting a specific mutation in cancer cells, has been safe in clinical studies. Patients with advanced non-small cell lung cancer (NSCLC) and colorectal cancer have tolerated adagrasib well. Since adagrasib is already approved for some cancer patients, there is some confidence in its safety.

In contrast, less information is available about the safety of INCB099280. This study is in an early phase, focusing primarily on assessing the safety of the drug combination. Early-phase trials closely monitor safety.

In summary, while adagrasib has a good safety record, INCB099280 is still under evaluation to ensure its safety when used with adagrasib. Participants in the trial will be closely monitored for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining INCB099280 and adagrasib for KRASG12C-mutated cancers because these treatments offer a fresh approach to targeting tumors. Unlike standard chemotherapy, which attacks all rapidly dividing cells, adagrasib specifically targets the KRASG12C mutation, a common driver in certain lung and colorectal cancers. INCB099280 is designed to work in tandem with adagrasib by enhancing its effects, potentially leading to more effective and precise cancer treatment. This combination has the potential to provide a more tailored treatment with fewer side effects compared to traditional options.

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

Research shows that adagrasib may effectively treat cancers with the KRASG12C mutation, such as non-small cell lung cancer (NSCLC) and colorectal cancer. Studies have found that it can help shrink tumors in these cancer types. Adagrasib targets and blocks the KRASG12C mutation, which often drives cancer growth. This trial tests INCB099280 in combination with adagrasib to determine if the combination can improve treatment outcomes for solid tumors with the KRASG12C mutation. While the effectiveness of INCB099280 alone is still under investigation, the combination is being studied in both the dose-finding and dose-expansion phases of this trial. ^{3 4 5 6 7}

Who Is on the Research Team?

Incyte Medical Monitor

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have a specific mutation called KRASG12C. Participants must have certain types of cancer like NSCLC or CRC, depending on the study part they're in, and should have tried some treatments already without success. They need to be relatively healthy otherwise, with an expected lifespan over 3 months and no serious recent infections or other cancers.

Inclusion Criteria

You are not planning to have a baby during the study.

Estimated life expectancy > 3 months

I have NSCLC and was treated with both anti-PD-(L)1 and platinum-based chemotherapy.

Exclusion Criteria

Laboratory values outside the Protocol-defined ranges

I have had chest radiation of more than 30 Gy in the last 6 months.

I haven't taken antibiotics in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

INCB099280 administered in combination with adagrasib to identify dose(s) for further evaluation

4 weeks

Dose Expansion

Up to 80 participants enrolled in disease-specific cohorts to evaluate selected doses

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years and 90 days

What Are the Treatments Tested in This Trial?

Interventions

• adagrasib
• INCB099280

Trial Overview The trial is testing how safe it is to use INCB099280 together with adagrasib on patients and figuring out the right doses. Researchers want to see if this combo can help people whose tumors haven't responded well to previous treatments.

How Is the Trial Designed?

Group I: Part 2: Dose Expansion Experimental Treatment 2 Interventions

Up to 80 participants will be enrolled in 1 of 2 disease-specific cohorts: Cohort A: previously treated KRASG12C mutated non-small cell lung cancer (NSCLC) Cohort B: previously treated KRASG12C-mutated colorectal cancer (CRC). Up to 3 doses may be selected from Part 1: Dose Finding for the Part 2: Dose Expansion.

Group II: Part 1: Dose Finding Experimental Treatment 2 Interventions

INCB099280 administered in combination with adagrasib in participants with previously treated KRAS glutamine to cysteine mutation at codon 12 (KRASG12C) mutant advanced solid tumors, will be evaluated to identify dose(s) for further evaluation in the dose expansion phase of the study.

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Mirati Therapeutics Inc.

Industry 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

Published Research Related to This Trial

In a phase II study involving 33 patients with recurrent glioblastoma, dovitinib did not show efficacy in prolonging progression-free survival (PFS) at 6 months, with only 12% in the anti-angiogenic naïve group achieving this compared to 0% in the pretreated group.

The study revealed significant toxicity, with 67% of patients experiencing grade 3 toxicities and 15% experiencing grade 4 toxicities, indicating that while dovitinib was not effective, it did pose safety concerns for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of Dovitinib in recurrent glioblastoma. Sharma, M., Schilero, C., Peereboom, DM., et al.[2020]

In a pilot study involving 13 patients with advanced melanoma, breast cancer, and colon cancer, the drug PD-0325901 showed significant tolerability issues, particularly at doses of 15 mg twice daily or higher, leading to early termination of the study due to adverse effects like gait disturbance and memory impairment.

Despite the safety concerns, one patient achieved a complete response and five had stable disease, suggesting that PD-0325901 may have preliminary antitumor activity, warranting further investigation at lower doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer. Boasberg, PD., Redfern, CH., Daniels, GA., et al.[2021]

Adavosertib, when combined with carboplatin, showed a high overall response rate of 66.7% in patients with platinum-resistant ovarian cancer, indicating promising efficacy for this treatment combination.

However, the combination therapy resulted in significant hematologic toxicities, such as neutropenia and anemia, suggesting that while adavosertib is effective, careful monitoring and further optimization of treatment protocols are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adavosertib with Chemotherapy in Patients with Primary Platinum-Resistant Ovarian, Fallopian Tube, or Peritoneal Cancer: An Open-Label, Four-Arm, Phase II Study. Moore, KN., Chambers, SK., Hamilton, EP., et al.[2022]

In the ADAURA study, adjuvant osimertinib significantly improved disease-free survival in patients with resected stage IB to IIIA EGFR-mutated non-small cell lung cancer (NSCLC) compared to placebo, with a median treatment duration of 35.8 months for osimertinib versus 25.1 months for placebo.

After three years of treatment, osimertinib showed no new safety concerns, and patients maintained their health-related quality of life, indicating that osimertinib is both effective and tolerable for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Safety, Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial. John, T., Grohé, C., Goldman, JW., et al.[2023]

In a clinical trial involving 55 patients with advanced solid tumors, the PD-1 inhibitor dostarlimab was found to be well tolerated in both doublet and triplet combination therapies, with no new safety concerns arising.

The triplet combinations showed higher disease control rates compared to doublets, with preliminary antitumor activity observed in various combinations, indicating potential for improved efficacy in treating advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin-paclitaxel, with or without bevacizumab in patients with advanced cancer. Yap, TA., Bessudo, A., Hamilton, E., et al.[2022]

The combination of lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, shows promising antitumor activity and durable responses in various solid tumors, as indicated by preliminary results from the LEAP clinical trial program.

This combination therapy has a manageable safety profile, suggesting it could be a valuable new treatment option for solid cancers that currently have limited therapeutic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Taylor, MH., Schmidt, EV., Dutcus, C., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06039384

NCT06039384 | A Study of INCB099280 in Combination ... The purpose of this study is to evaluate the safety and tolerability of INCB099280 in combination with adagrasib and to establish the MTD or identify RDE(s) ...

2. fightcolorectalcancer.org fightcolorectalcancer.org/clinical-trial/a-study-of-incb099280-in-combination-with-adagrasib-in-adults-with-advanced-solid-tumors-harboring-a-krasg12c-mutation/

A Study of INCB099280 in Combination With Adagrasib ... * KRASG12C-mutated solid malignancy determined by a sponsor-approved assay using either tumor tissue or ctDNA. * Histologically confirmed malignant solid tumor ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10852394/

Adagrasib in Advanced Solid Tumors Harboring a KRASG12C ... Adagrasib, a KRASG12C inhibitor, has demonstrated clinical activity in patients with KRASG12C-mutated non–small-cell lung cancer (NSCLC) and colorectal cancer ( ...

4. clinicaltrials.eu clinicaltrials.eu/inn/adagrasib/

Adagrasib – Application in Therapy and Current Clinical ... Adagrasib is an investigational drug being studied in clinical trials for the treatment of various cancers, particularly those with KRAS G12C mutations. This ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S104084282400297X

KRAS mutations in advanced non-small cell lung cancer Nowadays, sotarasib and adagrasib received the approval for the treatment of advanced NSCLC patients with KRASG12C mutation who progressed to chemotherapy and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06039384

NCT06039384 | A Study of INCB099280 in Combination ... The purpose of this study is to evaluate the safety and tolerability of INCB099280 in combination with adagrasib and to establish the MTD or identify RDE(s) ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT493874

Clinical outcomes and safety profile of adagrasib in KRAS ... However, Adagrasib, a selective KRAS G12C inhibitor, has demonstrated promising efficacy and safety in clinical studies. This single-arm meta-analysis ...