Study Of CBX-12 In Subjects With Advanced Or Metastatic Refractory Solid Tumors

Study Overview

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

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.

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.

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

DRUG: CBX-12

CBX-12-101

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-05-21	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-01-21
First Submitted that Met QC Criteria 2021-05-21	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-01-23
First Posted (ACTUAL) 2021-05-26	Results First Posted N/A	Last Verified 2025-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase 1 Schedule B Dose Escalation (Daily Dosing x 3) CBX-12 administered on a daily x 3, 3 week schedule	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
EXPERIMENTAL: Phase 1 Schedule C Dose Escalation (Once Weekly Dosing ) CBX-12 administered once weekly, 4 week schedule	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
EXPERIMENTAL: Phase 2 Ovarian Cancer Expansion Cohort CBX-12 administered TBD
EXPERIMENTAL: Phase 2 Metastatic Breast Expansion Cohort CBX-12 administered TBD
EXPERIMENTAL: Phase 1 Schedule A Dose Escalation (Daily Dosing x 5) CBX-12 administered on a daily x 5, 3 week schedule	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
EXPERIMENTAL: Phase 1 Modified Schedule B Dose Escalation (Once Every 3 weeks) CBX-12 administered once every 3 weeks	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

Primary Outcome Measures	Measure Description	Time Frame
Phase 1: Incidence of treatment-emergent adverse events (TEAEs)	NCI CTCAE v5.0	Through the end of study, estimated as 6 months
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
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
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
Phase 2: Overall response rate (ORR)	ORR Based on RECIST v1.1	Through the end of study, estimated as 6 months

Secondary Outcome Measures	Measure Description	Time Frame
Maximum concentration of CBX-12	PK Analysis	5 days
Area under the curve from 0-24 hours of CBX-12	PK Analysis	5 days
Time to maximum concentration of CBX-12	PK Analysis	5 days
Half-life of CBX-12	PK Analysis	5 days
Clearance (CL) of CBX-12	PK Analysis	5 days
Apparent Volume of Distribution at Steady State (Vss) CBX-12	PK Analysis	5 days
Phase 1: ORR	Based on RECIST v1.1	Through the end of study, estimated as 6 months
Duration of Response (DoR)	Based on RECIST v1.1	Through the end of study, estimated as 6 months
Progression-free Survival (PFS)	Based on RECIST v1.1	Through the end of study, estimated as 6 months
Phase 2: Incidence of TEAEs	NCI CTCAE v5.0	Through the end of study, estimated as 6 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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)

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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