Study of INCB123667 in Subjects With Advanced Solid Tumors
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| ClinicalTrials.gov Identifier: NCT05238922 |
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Recruitment Status :
Recruiting
First Posted : February 14, 2022
Last Update Posted : December 13, 2022
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Sponsor:
Incyte Corporation
Information provided by (Responsible Party):
Incyte Corporation
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Brief Summary:
This is an open-label, dose-escalation and dose-expansion study to determine the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy of INCB123667 when administered as monotherapy at the RDE(s) in participants with selected advanced or metastatic solid tumors. Part 1A (dose escalation) will determine the recommended dose of INCB123667 for expansion (RDE) and the maximum tolerated dose (MTD). Part 1B (cohort dose expansion phase) will further explore antitumor activity of INCB123667 as a monotherapy in 4 tumor-specific cohorts at the RDE(s) defined in Part 1A.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Solid Tumors | Drug: INCB0123667 | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 155 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | Part 1a will be dose escalation using a statistical hybrid design to identify the RDE(s), and the starting dose of INCB123667 will be 50mg QD. Part 1B will be dose expansion portion will administer the RDE(s) defined in Part 1A to 4 Disease Groups: 1) Gynecological Tumors, 2) GI Tumors, 3) Breast Cancer, and 4) Tumor Agnostic. |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1, Open-Label, Multicenter Study of INCB123667 as Monotherapy in Participants With Selected Advanced Solid Tumors |
| Actual Study Start Date : | July 5, 2022 |
| Estimated Primary Completion Date : | April 27, 2024 |
| Estimated Study Completion Date : | July 30, 2026 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Phase 1a Dose Escalation
INCB123667 will be administered at a protocol defined starting regimen once daily (QD) orally in 28-day cycles. Subsequent dose regimens will be determined during study conduct. |
Drug: INCB0123667
25 mg tablets |
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Experimental: Phase 1b: Dose Expansion Cohort Disease Group 1 Gynecological Tumors
INCB123667 will be administered at the recommended dose or doses for expansion (RDE[s]) for advanced or metastatic solid tumors. Participants in this group will have gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma or clear cell ovarian cancer, or endometrial adenocarcinoma, uterine carcinosarcoma, or uterine papillary serous carcinoma).
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Drug: INCB0123667
25 mg tablets |
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Experimental: Phase 1b: Dose Expansion Cohort Disease Group 2 GI Tumors
INCB123667 will be administered at the recommended dose or doses for expansion (RDE[s]) for advanced or metastatic solid tumors. Participants in this group will have gastrointestinal tumors (gastric, GEJ, and esophageal adenocarcinomas).
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Drug: INCB0123667
25 mg tablets |
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Experimental: Phase 1b: Dose Expansion Cohort Disease Group 3 Breast Cancer
INCB123667 will be administered at the recommended dose or doses for expansion (RDE[s]) for advanced or metastatic solid tumors. Participants in this group will have breast cancer (participants with HR-positive/HER2-negative breast cancer who have had disease progression on or been intolerant of therapies known to confer clinical benefit, including a CDK4/6 inhibitor).
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Drug: INCB0123667
25 mg tablets |
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Experimental: Phase 1b: Dose Expansion Cohort Disease Group 4 Tumor Agnostic
at the recommended dose or doses for expansion (RDE[s]) for advanced or metastatic solid tumors. This group will include participants who have had disease progression on prior standard treatment or are intolerant to or ineligible for standard treatment or there is no available treatment to improve the participant's disease outcome.
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Drug: INCB0123667
25 mg tablets |
Primary Outcome Measures :
- Part 1A : Occurrence of Dose Limiting Toxicities (DLTs) [ Time Frame: Up to Day 28 ]Toxicities occurring during the first treatment cycle, Part 1a, will define tolerability. DLTs will be assessed for severity by the investigator using CTCAE v5.0 criteria.
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Up to 12 months ]TEAE is any Adverse Event (AE) either reported for the first time or worsening of a pre-existing event after first dose of study drug.
- Number of Participants with Dose Interruptions due to TEAE [ Time Frame: Up to 12 months ]Participants will receive dose reductions of INCB123667 according to lab guidelines. Treatment may be delayed for up to 2 weeks to allow for resolution of toxicity.
- Number of Participants who Undergo Dose Reductions due to TEAE [ Time Frame: Up to 12 months ]Participants will receive dose reductions according to lab guidelines. Treatment may be delayed for up to 2 weeks to allow for resolution of toxicity.
- Number of Participants Discontinue study due to TEAE [ Time Frame: Up to 12 months ]TEAE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Secondary Outcome Measures :
- PK parameters: Cmax [ Time Frame: Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days) ]Defines as the maximum (peak) plasma drug concentration
- PK parameters: tmax [ Time Frame: Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days) ]Defined as the time to reach maximum (peak) plasma concentration following drug administration
- PK parameters: Ctau [ Time Frame: Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days) ]Ctau is defined as concentration at the end of the dosing interval
- PK Parameters: AUC [ Time Frame: Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days) ]Defined as the area under the plasma concentration-time curve
- PK Parameters: CL (or CL/F) [ Time Frame: Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days) ]Defined as the apparent total body clearance of the drug from plasma
- PK Parameters: Vz (or Vz/F) [ Time Frame: Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days) ]Defined as apparent volume of distribution during terminal phase
- PK Parameters: t1/2 [ Time Frame: Cycle 1 Days 1, 8, and 15; Cycle 2 Days 1 and 8 (each cycle is 28 days) ]Defined as Elimination half-life (to be used in one-or noncompartmental model)
- Objective Response Rate (ORR) [ Time Frame: Up to 12 months ]Defined as having Complete Response (CR) or Partial Response (PR), as determined by the investigator by radiographic disease assessment according to RECIST v1.1.
- Disease Control Response (DCR) [ Time Frame: Up to 12 months ]Defined as having CR, PR, or Stable Disease (SD) as determined by the investigator by radiographic disease assessment according to RECIST v1.1.
- Duration of Response (DOR) [ Time Frame: Up to 12 months ]Defined as the time from earliest date of disease response (Completed Rresponse or Partial Response) until earliest date of disease progression as determined by the investigator by radiographic disease assessment according to RECIST v1.1 or death due to any cause if occurring sooner than progression.
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| Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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.
Participants in Part 1B:
- 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.
- 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).
- 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.
- Untreated brain or central nervous system (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).
- 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 > 1 year after treatment with curative intent.
- Specific Lab values
- Significant concurrent, uncontrolled medical conditions, such as liver disease and gastrointestinal disorders.
- Has not recovered to ≤ Grade 1 from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study drug.
- Prior treatment with any CDK2 inhibitor.
- Any change in endocrine therapy within 5 half-lives or 28 days (whichever is shorter) before the first dose of study drug or any administration of targeted therapy, antibody, or hypomethylating agent to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study drug.
- Any major surgery within 28 days before the first dose of study drug.
- Any prior radiation therapy within 28 days before the first dose of study drug.
- Undergoing treatment with another investigational medication or having been treated with an investigational medication within 5 half-lives or 28 days (whichever is shorter) before the first dose of study drug.
- Undergoing treatment with any potent CYP3A4/CYP3A5 inhibitor or inducer (University of Washington School of Pharmacy 2020) or having been treated with a potent CYP3A4/CYP3A5 inhibitor or inducer within 5 half-lives or 28 days (whichever is shorter) before the first dose of study drug.
- Known or suspected SARS-CoV-2 infection at the time of enrollment.
- Active HBV or HCV infection that requires treatment. HBV DNA and HCV RNA must be undetectable. Participants who have cleared a prior HBV infection (defined as HBsAg negative, HBsAg antibody positive, and anti-HBc antibody positive) are eligible for the study.
- Known history of HIV (HIV 1/2 antibodies).
- Known hypersensitivity or severe reaction to any component of study drug(s) or formulation components.
- Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
- Current use of certain prohibited medications.
- Women who are pregnant or breastfeeding.
- For studies conducted in France, the following participants are excluded: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05238922
Contacts
| Contact: Incyte Corporation Call Center (US) | 1.855.463.3463 | medinfo@incyte.com | |
| Contact: Incyte Corporation Call Center (ex-US) | +800 00027423 | eumedinfo@incyte.com |
Locations
Show 35 study locations
Sponsors and Collaborators
Incyte Corporation
Investigators
| Study Director: | Liz Croft Richards | Incyte Corporation |
| Responsible Party: | Incyte Corporation |
| ClinicalTrials.gov Identifier: | NCT05238922 |
| Other Study ID Numbers: |
INCB 123667-101 |
| First Posted: | February 14, 2022 Key Record Dates |
| Last Update Posted: | December 13, 2022 |
| Last Verified: | December 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Incyte Corporation:
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advanced solid tumors metastatic solid tumors Gynecological Tumors, GI Tumors, Breast Cancer, Tumor Agnostic cyclin E1 gene epithelial ovarian carcinoma fallopian carcinoma |
primary peritoneal carcinoma clear cell ovarian cancer endometrial adenocarcinoma uterine carcinosarcoma uterine papillary serous carcinoma gastrointestinal tumors gastric adenocarcinomas GEJ adenocarcinomas esophageal adenocarcinomas |
Additional relevant MeSH terms:
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Neoplasms |