Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors

NCT ID: NCT04902872

Last Updated: 2025-01-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-03
• Study Completion Date: 2025-06-30

Brief Summary

This is a first-in-human, Phase 1/2 open-label, multicenter, dose-escalation, safety, pharmacokinetics (PK), and biomarker study of CBX-12 in subjects with advanced or metastatic refractory solid tumors.

Detailed Description

Phase 1 is the dose-escalation portion of the study in which the safety and tolerability of three dosing schedules of CBX-12 will be evaluated. Subjects in Part A will be treated with CBX-12 on a daily x 5 every 3 weeks schedule (treatment in Part A was discontinued in October 2021). Subjects in Phase 1 Part B will be treated with CBX-12 on a daily x 3 every 3 weeks schedule. Subjects in Phase 1 Part C will be treated with CBX-12 once weekly. Subjects in Phase 1 Modified Part B will be treated with CBX-12 once every 3 weeks.

For all parts in Phase 1, after all subjects in a cohort have completed treatment through the DLT period or discontinued treatment due to a DLT, the SRC, composed of the Investigators who have enrolled subjects in the current cohort(s), the study Medical Monitor and ad hoc members (e.g., other Investigators, a statistician) as needed, will review all available safety data, including DLTs and all available PK data for that cohort and make dose-level recommendations.

Once the recommended phase 2 dose (RP2D) has been established in Part B, Part C and Modified Part B, Phase 2 expansion cohorts may open.

Conditions

Solid Tumor, Adult; Epithelial Ovarian Cancer; Small Cell Lung Carcinoma; Breast Cancer; Colorectal Cancer; Pancreas Cancer; Appendix Cancer; Non-small Cell Lung Cancer; Gastric Cancer; Esophagus Cancer; Urothelial Carcinoma; Sarcoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Schedule B Dose Escalation (Daily Dosing x 3)

CBX-12 administered on a daily x 3, 3 week schedule

Group Type: EXPERIMENTAL

CBX-12

Intervention Type: DRUG

CBX-12 is an alphalex construct which consists of a low-pH insertion peptide, a self-immolating linker, and exatecan as the pharmacologically active moiety

Phase 1 Schedule C Dose Escalation (Once Weekly Dosing )

CBX-12 administered once weekly, 4 week schedule

Group Type: EXPERIMENTAL

CBX-12

Intervention Type: DRUG

CBX-12 is an alphalex construct which consists of a low-pH insertion peptide, a self-immolating linker, and exatecan as the pharmacologically active moiety

Phase 2 Ovarian Cancer Expansion Cohort

CBX-12 administered TBD

Group Type: EXPERIMENTAL

CBX-12

Intervention Type: DRUG

CBX-12 is an alphalex construct which consists of a low-pH insertion peptide, a self-immolating linker, and exatecan as the pharmacologically active moiety

Phase 2 Metastatic Breast Expansion Cohort

CBX-12 administered TBD

Group Type: EXPERIMENTAL

CBX-12

Intervention Type: DRUG

CBX-12 is an alphalex construct which consists of a low-pH insertion peptide, a self-immolating linker, and exatecan as the pharmacologically active moiety

Phase 1 Schedule A Dose Escalation (Daily Dosing x 5)

CBX-12 administered on a daily x 5, 3 week schedule

Group Type: EXPERIMENTAL

CBX-12

Intervention Type: DRUG

CBX-12 is an alphalex construct which consists of a low-pH insertion peptide, a self-immolating linker, and exatecan as the pharmacologically active moiety

Phase 1 Modified Schedule B Dose Escalation (Once Every 3 weeks)

CBX-12 administered once every 3 weeks

Group Type: EXPERIMENTAL

CBX-12

Intervention Type: DRUG

CBX-12 is an alphalex construct which consists of a low-pH insertion peptide, a self-immolating linker, and exatecan as the pharmacologically active moiety

Interventions

CBX-12

CBX-12 is an alphalex construct which consists of a low-pH insertion peptide, a self-immolating linker, and exatecan as the pharmacologically active moiety

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subject has a histologically- or cytologically-diagnosed solid tumor which is advanced or metastatic and which has progressed on or following at least one systemic therapy regimen administered for advanced or metastatic disease or for which no approved therapy exists. Subject's prior treatment should include all approved regimens that have demonstrated a survival advantage for the subject's disease, stage, and line of therapy.
• Has measurable disease per RECIST 1.1.
• An adequate tumor sample must be available from core needle biopsies obtained during the Screening Period and following the subject's most recent systemic therapy.
• Agrees to an on-treatment biopsy preferably of the same lesion from which the pre-CBX-12 treatment sample was obtained as long as the Investigator determines such biopsy can be performed with acceptable safety. (Removed Amd 4, date 31-Mar-2023)

Exclusion Criteria

• Cytotoxic chemotherapy, biologic agent, investigational agent, or radiation therapy less than or equal to 3 weeks prior to the first dose of CBX-12. The interval may be reduced to 2 weeks for bone only radiation therapy or investigational agents not expected to be associated with adverse events (AEs) after 2 weeks of last administration, with Medical Monitor approval.
• Small-molecule kinase inhibitors or hormonal agents less than or equal to 14 days prior to the first dose of CBX-12.
• Subjects who are currently receiving any other anti cancer or investigational agent(s).
• Clinically significant intercurrent disease.
• Subjects with primary central nervous system (CNS) tumors or clinically active CNS metastases or carcinomatous meningitis. Subjects with stable brain metastasis may be enrolled with Medical Monitor approval.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cybrexa Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Yale Cancer Center

New Haven, Connecticut, United States

NEXT Oncology

Austin, Texas, United States

MD Anderson Cancer Center

Houston, Texas, United States

NEXT Oncology

San Antonio, Texas, United States

Countries

United States

Other Identifiers

CBX-12-101

Identifier Type: -

Identifier Source: org_study_id