INCB099280 + Adagrasib for Solid Tumors

Recruiting at 47 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

6 Participants Needed

Trial Summary

What is the purpose of this trial?

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) for the combination of INCB099280 and adagrasib.

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.

What data supports the effectiveness of the drug combination INCB099280 + Adagrasib for solid tumors?

The LEAP program shows that combining drugs that block certain signals in tumors can enhance immune response and reduce tumor growth in various solid tumors, suggesting that similar combinations like INCB099280 + Adagrasib might also be effective. ^{1 2 3 4 5}

What makes the drug combination of INCB099280 and adagrasib unique for treating solid tumors?

The combination of INCB099280 and adagrasib is unique because it targets specific pathways involved in cancer growth, potentially offering a novel approach compared to standard treatments. This combination may provide a new option for patients with solid tumors, especially if existing treatments are limited or ineffective. ^{6 7 8 9 10}

Research Team

Incyte Medical Monitor

Principal Investigator

Incyte Corporation

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer. [2021]

3. England 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. [2022]

4. United States 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. [2022]

5. United States 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

ICON 9-an international phase III randomized study to evaluate the efficacy of maintenance therapy with olaparib and cediranib or olaparib alone in patients with relapsed platinum-sensitive ovarian cancer following a response to platinum-based chemotherapy. [2021]

7. England pubmed.ncbi.nlm.nih.gov

A review of iniparib in ovarian cancer. [2014]

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy, safety, pharmacokinetics, and biomarkers of cediranib monotherapy in advanced hepatocellular carcinoma: a phase II study. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Phase II study of Dovitinib in recurrent glioblastoma. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

The Poly (ADP-ribose) polymerase inhibitor olaparib and pan-ErbB inhibitor neratinib are highly synergistic in HER2 overexpressing epithelial ovarian carcinoma in vitro and in vivo. [2023]