Study of INCB123667 in Subjects With Advanced Solid Tumors

Incyte

Status and phase: Enrolling; Phase 1

Conditions: Solid Tumors

Treatments: Drug: Palbociclib; Drug: Olaparib; Drug: Fulvestrant; Drug: Bevacizumab; Drug: Ribociclib; Drug: Paclitaxel; Drug: INCB0123667

Study type: Interventional

Funder types: Industry

Identifiers

NCT05238922

INCB 123667-101

Details and patient eligibility

About

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 and in combination with anticancer therapies in participants with selected advanced or metastatic solid tumors. This study will consist of 2 parts. In Part 1, INCB123667 will be administered as monotherapy and in Part 2, INCB123667 will be administered in combination with anticancer therapies of interest. Each part will comprise a dose escalation portion (Parts 1a and 2a, respectively) and a dose-expansion portion (Parts 1b and 2b, respectively).

Enrollment: 604 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults aged 18 years or older at the time of the signing of the ICF.
• 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.

For Part 1:

Participants in Part 1A (dose escalation): Histologically or cytologically confirmed advanced or metastatic solid tumors.

Participants in Part 1B (dose expansion):

• Disease Group 1: Ovarian/Fallopian/Primary Peritoneal Cancer
• Disease Group 2: Endometrial/Uterine Cancer
• Disease Group 3: Gastric, GEJ, and esophageal carcinomas
• Disease Group 4: TNBC
• Disease Group 5: HR+/HER2- breast cancer
• Disease Group 6: Other tumor indications excluding bone cancers

For Part 2:

Participants in Part 2A (dose escalation): Histologically or cytologically confirmed advanced or metastatic solid tumors.

• TGA, TGC, TGE, TGF, and TGG: Participants with HR+/HER2- breast cancer or participants with a different tumor.
• TGB and TGD: Participants with HR+/HER2- breast cancer.

Participants in Part 2b (dose expansion):

• TGH and TGJ:

  • Participants with HR+/HER2- breast cancer.
  • Participants with any other advanced or metastatic solid tumor.

• TGI and TGK:

  • Participants with HR+/HER2- breast cancer.

• TGL, TGM and TGN:

  • Participants with advanced or metastatic epithelial ovarian/fallopian/primary peritoneal carcinoma.

• Measurable lesions by CT or MRI based on RECIST v1.1 criteria.

Exclusion criteria

• History of clinically significant or uncontrolled cardiac disease.
• History or presence of an ECG abnormality that, in the investigator's opinion, is clinically meaningful.
• 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.
• 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.
• Specific laboratory values.
• Significant concurrent, uncontrolled medical conditions, including but not limited to Hepatic and Gastrointestinal.
• 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.
• Active HBV or HCV infection that requires treatment.
• Known history of HIV.
• Known hypersensitivity or severe reaction to any component of study treatment or formulation components.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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604 participants in 21 patient groups

Phase 1a Dose Escalation

Experimental group

Description:

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.

Treatment:

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 1

Experimental group

Description:

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) will enroll in this group.

Treatment:

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 2

Experimental group

Description:

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with Endometrial/Uterine cancer will enroll in this group.

Treatment:

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 3

Experimental group

Description:

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with gastric, Gastro Esophageal Junction (GEJ), and esophageal adenocarcinomas will enroll in this group.

Treatment:

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 4

Experimental group

Description:

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with Triple Negative Breast Cancer(TNBC) will enroll in this group.

Treatment:

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 5

Experimental group

Description:

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors. Participants with HR+/HER2- breast cancer who have had disease progression on or been intolerant of a CDK4/6 inhibitor will enroll in this group.

Treatment:

Drug: INCB0123667

Phase 1b: Dose Expansion Cohort Disease Group 6

Experimental group

Description:

INCB123667 will be administered at the recommended dose or doses for expansion (RDE\[s\]) for advanced or metastatic solid tumors will enroll in this group.

Treatment:

Drug: INCB0123667

Phase 2a Dose Escalation Treatment Group A (TGA)

Experimental group

Description:

INCB123667 administered in combination with palbociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Treatment:

Drug: INCB0123667

Drug: Palbociclib

Phase 2a Dose Escalation Treatment Group B (TGB)

Experimental group

Description:

INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol.

Treatment:

Drug: INCB0123667

Drug: Fulvestrant

Drug: Palbociclib

Phase 2a Dose Escalation Treatment Group C (TGC)

Experimental group

Description:

INCB123667 administered in combination with ribociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Treatment:

Drug: INCB0123667

Drug: Ribociclib

Phase 2a Dose Escalation Treatment Group D (TGD)

Experimental group

Description:

INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol.

Treatment:

Drug: INCB0123667

Drug: Ribociclib

Drug: Fulvestrant

Phase 2a Dose Escalation Treatment Group E (TGE)

Experimental group

Description:

INCB123667 administered in combination with bevacizumab at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Treatment:

Drug: INCB0123667

Drug: Bevacizumab

Phase 2a Dose Escalation Treatment Group F (TGF)

Experimental group

Description:

INCB123667 administered in combination with olaparib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Treatment:

Drug: INCB0123667

Drug: Olaparib

Phase 2a Dose Escalation Treatment Group G (TGG)

Experimental group

Description:

INCB123667 administered in combination with paclitaxel at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Treatment:

Drug: INCB0123667

Drug: Paclitaxel

Phase 2b Dose Expansion Treatment Group H (TGH)

Experimental group

Description:

INCB123667 administered in combination with palbociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Treatment:

Drug: INCB0123667

Drug: Palbociclib

Phase 2b Dose Expansion Treatment Group I (TGI)

Experimental group

Description:

INCB123667 administered in combination with palbociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol

Treatment:

Drug: INCB0123667

Drug: Fulvestrant

Drug: Palbociclib

Phase 2b Dose Expansion Treatment Group J (TGJ)

Experimental group

Description:

INCB123667 administered in combination with ribociclib at the recommended doses in participants with HR+/HER2- breast cancer and in participants with a different tumor as defined in the protocol.

Treatment:

Drug: INCB0123667

Drug: Ribociclib

Phase 2b Dose Expansion Treatment Group K (TGK)

Experimental group

Description:

INCB123667 administered in combination with ribociclib and fulvestrant at the recommended doses in participants with HR+/HER2- breast cancer as defined in the protocol.

Treatment:

Drug: INCB0123667

Drug: Ribociclib

Drug: Fulvestrant

Phase 2b Dose Expansion Treatment Group L (TGL)

Experimental group

Description:

INCB123667 administered in combination with bevacizumab at the recommended doses in participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) as defined by the protocol.

Treatment:

Drug: INCB0123667

Drug: Bevacizumab

Phase 2b Dose Expansion Treatment Group M (TGM)

Experimental group

Description:

INCB123667 administered in combination with olaparib at the recommended doses in participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) as defined by the protocol.

Treatment:

Drug: INCB0123667

Drug: Olaparib

Phase 2b Dose Expansion Treatment Group N (TGN)

Experimental group

Description:

INCB123667 administered in combination with weekly paclitaxel at the recommended doses in participants with gynecologic tumors (epithelial ovarian/fallopian/primary peritoneal carcinoma) as defined by the protocol.

Treatment:

Drug: INCB0123667

Drug: Paclitaxel