INCB 123667-101: A phase I, Open-Label, Multicenter Study of INCB123667 as Monotherapy in Participants With Selected Advanced Solid Tumors
Histologically or citologically confirmed advanced or metastatic solid tumors
Dose escalation and Dose expansion (2nd line)
INCB123667 (selective inhibitor of CDK2) 50 mg QD in 28-day continuous treatment cycles
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Primary objective :
To evaluate the safety and tolerability and determine the MTD and RDE(s) of INCB123667 as monotherapy in participants with selected advanced or metastatic solid tumors.
Inclusion criteria :
- Ability to comprehend and willingness to sign a written ICF for the study.
- Adults age 18 years or older and 20 years or older in Japan at the time of signing the ICF.
- Willing and able to conform to and comply with all Protocol requirements, including all scheduled visits and Protocol procedures.
- Life expectancy greater than 12 weeks.
- ECOG performance status score of 0 or 1.
- Disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, or no available treatment to improve the disease outcome.
- Availability of a baseline archival tumor specimen or willingness to undergo a pretreatment and an on-treatment tumor biopsy (core or excisional) as applicable to
obtain the specimen.
- Diagnoses as follows:
a. For participants in Part 1a (dose escalation): Histologically or cytologically confirmed advanced or metastatic solid tumors. Documented cyclin E1 overexpression or CCNE1 amplification from a qualified local laboratory test is preferred but not mandatory.
b. For participants in Part 1b (dose expansion): Tumor tissue with cyclin E1 overexpression or CCNE1 amplification as determined by a qualified local laboratory or central confirmation of cyclin E1 overexpression and with any of the following histologically or cytologically confirmed indications:
− Disease Group 1: Gynecologic malignancies
− Disease Group 2: Gastrointestinal malignancies
− Disease Group 3: Breast cancer
− Disease Group 4: Other tumor indications
- Measurable lesions by CT or MRI based on RECIST v1.1 criteria that are considered nonamenable to surgery or other curative treatments or procedures.
- Ability to swallow and retain oral medication.
- Willingness to avoid pregnancy or fathering children
Exclusion criteria :
- History of clinically significant or uncontrolled cardiac disease, including recent (within the last 12 months) unstable angina pectoris or acute myocardial infarction, or New York Heart Association Class III or IV cardiac disease, including preexisting clinically significant ventricular arrhythmia, congestive heart failure, cardiomyopathy not
controlled by medication, or other clinically significant heart disease (ie, ≥ uncontrolled Grade 3 hypertension). Participants with a pacemaker and well-controlled rhythm for at least 1 month before the first dose of study drug will be allowed.
- History or presence of an ECG abnormality that, in the investigator's opinion, is clinically meaningful. Screening QTcF interval > 450 milliseconds is excluded; in the event that a single QTc is > 450 milliseconds, the participant may enroll if the average QTc for the 3 ECGs is < 450 milliseconds.
- Presence of chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment. Participants with acute infection requiring antibiotic, antifungal, or antiviral treatment should delay screening/enrollment until the course of antibiotic, antifungal, or antiviral therapy has been completed and the infection is no longer active.
- Untreated brain or CNS metastases or brain or CNS metastases that have progressed (eg, evidence of new or enlarging brain metastasis or new neurological symptoms
attributable to brain or CNS metastases). Note: Participants who have previously treated and clinically stable brain or CNS metastases (without evidence of progression by imaging for at least 4 weeks before the first dose of study drug and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastasis or CNS edema, and have not required steroids for at least 7 days before study drug are eligible.
- Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of the first dose of study drug with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease-free for Lausanne> 1 year after treatment with curative intent.
- Participants with laboratory values at screening defined in Table 8.