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

Breast Cancer Clinical Trial

Official title:

A Phase 1/2 Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04902872
• Other study ID #: CBX-12-101
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 3, 2021
• Est. completion date: September 2024

Study information

• Verified date: January 2024
• Source: Cybrexa Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: September 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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.

Related Conditions & MeSH terms

• Appendiceal Neoplasms
• Appendix Cancer
• Breast Cancer
• Carcinoma
• Carcinoma, Ovarian Epithelial
• Colorectal Cancer
• Epithelial Ovarian Cancer
• Esophageal Neoplasms
• Esophagus Cancer
• Gastric Cancer
• Non-small Cell Lung Cancer
• Pancreas Cancer
• Pancreatic Neoplasms
• Sarcoma
• Small Cell Lung Carcinoma
• Solid Tumor, Adult
• Urothelial Carcinoma

Intervention

Drug:
• 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

Locations

Country	Name	City	State
United States	NEXT Oncology	Austin	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Yale Cancer Center	New Haven	Connecticut
United States	NEXT Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Cybrexa Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1: Incidence of treatment-emergent adverse events (TEAEs)	NCI CTCAE v5.0	Through the end of study, estimated as 6 months
Primary	Phase 1: Recommended Phase 2 Dose for Daily x 3 every 3 weeks schedule of CBX-12 (Schedule B)	Safety Review Committee Analysis of Safety and PK Data	15 months
Primary	Phase 1: Recommended Phase 2 Dose for Once Weekly schedule of CBX-12 (Schedule C)	Safety Review Committee Analysis of Safety and PK Data	15 months
Primary	Phase 1: Recommended Phase 2 Dose for Once Every 3 Weeks schedule of CBX-12 (Modified Schedule B)	Safety Review Committee Analysis of Safety and PK Data	15 months
Primary	Phase 2: Overall response rate (ORR)	ORR Based on RECIST v1.1	Through the end of study, estimated as 6 months
Secondary	Maximum concentration of CBX-12	PK Analysis	5 days
Secondary	Area under the curve from 0-24 hours of CBX-12	PK Analysis	5 days
Secondary	Time to maximum concentration of CBX-12	PK Analysis	5 days
Secondary	Half-life of CBX-12	PK Analysis	5 days
Secondary	Clearance (CL) of CBX-12	PK Analysis	5 days
Secondary	Apparent Volume of Distribution at Steady State (Vss) CBX-12	PK Analysis	5 days
Secondary	Phase 1: ORR	Based on RECIST v1.1	Through the end of study, estimated as 6 months
Secondary	Duration of Response (DoR)	Based on RECIST v1.1	Through the end of study, estimated as 6 months
Secondary	Progression-free Survival (PFS)	Based on RECIST v1.1	Through the end of study, estimated as 6 months
Secondary	Phase 2: Incidence of TEAEs	NCI CTCAE v5.0	Through the end of study, estimated as 6 months