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A Phase 1 Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutatio

Phase 1
Recruiting
Conditions
Advanced Solid Tumors Harboring a KRASG12C Mutation
MedDRA version: 21.1Level: PTClassification code: 10029515Term: Non-small cell lung cancer recurrent Class: 100000004864
MedDRA version: 21.1Level: PTClassification code: 10059515Term: Non-small cell lung cancer metastatic Class: 100000004864
MedDRA version: 21.1Level: PTClassification code: 10029522Term: Non-small cell lung cancer stage IV Class: 100000004864
MedDRA version: 21.1Level: PTClassification code: 10061873Term: Non-small cell lung cancer Class: 100000004864
MedDRA version: 20.0Level: LLTClassification code: 10010036Term: Colorectal carcinoma Class: 10029104
Therapeutic area: Diseases [C] - Neoplasms [C04]
Registration Number
CTIS2023-503223-26-00
Lead Sponsor
Incyte Corp.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
125
Inclusion Criteria

Ability to comprehend the participant information and willingness to sign a written ICF for the study., ECOG performance status of 0 or 1., Estimated life expectancy > 3 months., Willingness to avoid pregnancy or fathering children based on the criteria below. a.Men must agree to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through 100 days after the last dose of study drug (or longer as appropriate based on country-specific requirements) and must refrain from donating sperm during this period. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. b.Women of childbearing potential must do the following: ?Have a negative serum pregnancy test at screening and must agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through 190 days after the last dose of study treatment. Permitted methods that are at least 99% effective in preventing pregnancy (see Appendix A) should be communicated to the participants and their understanding confirmed. ?Refrain from donating oocytes from 30 days before the first dose of study drug until 90 days after the last dose. c.Women of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR = 12 months of amenorrhea and at least 50 years of age) are eligible., Men and women 18 years of age or older at the time of signing the ICF., KRASG12C-mutated solid malignancy determined by a sponsor-approved assay using either tumor tissue or ctDNA., Histologically confirmed malignant solid tumor with locally advanced and/or metastatic disease. a.Only participants with NSCLC will be enrolled into Part 2 Cohort A. b.Only participants with CRC will be enrolled into Part 2 Cohort B., Part 1: Disease progression on or after at least 1 prior systemic treatment. Participants must have received all available local standard of care therapies., Part 2 (Cohort A): Received at least 1 platinum-containing chemotherapy regimen that may include an anti–PD-1 inhibitor., Part 2 (Cohort B): Received at least 1 line of systemic therapy., Measurable disease according to RECIST v1.1., Known PD-L1 expression level in tumor. The PD-L1 expression level may have been determined at any point in the disease course using a commercially available assay or can be tested locally during the screening process (using a commercially available assay) and the results reported to the sponsor. If PD-L1 expression is unknown or cannot be tested locally, participants must be willing to provide tumor tissue (fresh or archival).

Exclusion Criteria

Another malignancy that is progressing or has progressed within the past 3 years and/or that requires treatment. Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, early-stage endometrial cancer that has been definitively treated, superficial bladder cancer, Gleason 6/7 treated prostate cancer, and ductal carcinoma in situ or lobular carcinoma in situ of the breast., History or evidence of interstitial lung disease, including noninfectious pneumonitis., Presence of a GI condition that may affect drug absorption., Active autoimmune disease requiring systemic treatment, including corticosteroids exceeding a daily dose of 10 mg of prednisone or equivalent., A diagnosis of immunodeficiency or receiving chronic systemic steroid therapy exceeding a daily dose of 10 mg of prednisone or equivalent., HIV infection with a CD4+ T-cell count < 200 cells/µL and/or a detectable viral load per parameters of assay and/or on an ART regimen containing a moderate or potent CYP3A4/CYP3A5 inhibitor or inducer and/or on a new ART regimen for less than 28 days prior to the initiation of study treatment., Active infection, including tuberculosis, requiring systemic therapy, with the exception of HIV as noted in Exclusion Criterion 14., History of organ transplantation, including allogeneic stem cell transplantation., Known hypersensitivity or severe reaction to any component of study drug or formulation components., Major surgery within 4 weeks of the start of study therapy or postoperative complications preventing the participant from adhering to protocol assessments and procedures., Presence of GI conditions that may affect drug absorption, as well as those that interfere with GI transit, including gastric bypass surgery, gastric sleeve, or gastric band., CNS metastases requiring treatment and/or leptomeningeal disease. a.Participants with untreated CNS metastases that are symptomatic, who require increasing doses of steroids and/or a steroid dose of more than 1 mg of dexamethasone daily (or equivalent), or with lesions with a significant amount of surrounding edema. b.Participants with previously treated CNS metastases that are progressing, who are not clinically stable within 2 weeks of the initiation of study treatment, or who require increasing doses of steroids and/or a steroid dose of more than 1 mg of dexamethasone daily (or equivalent)., Inability to swallow tablets., Receipt of systemic antibiotics within 28 days of the first dose of study treatment., Probiotic usage during screening and throughout the study treatment period., Receipt of a live-attenuated vaccine (such as measles, mumps, and rubella; chickenpox; some zoster; yellow fever; rabies; BCG; and typhoid vaccines) within 28 days of the planned start of study drug. Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live-attenuated vaccines and are not allowed. Note: If enrolled, participants should not receive live-attenuated vaccines during the study and up to 90 days after the last dose of study treatment (see Section 6.7.3)., Medication with any of the following characteristics that cannot be discontinued prior to the start of study treatment: moderate and potent CYP3A4/CYP3A5 inhibitors or inducers (see Appendix B), CYP3A substrates with a narrow therapeutic index, P-gp substrates with a narrow therapeutic index, inhibitors o

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
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