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

A Phase 1/2 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.

Study Overview

• Status: Completed
• Conditions: Sarcoma; Breast Cancer; Small Cell Lung Carcinoma; Gastric Cancer; Colorectal Cancer; Epithelial Ovarian Cancer; Non-small Cell Lung Cancer; Pancreas Cancer; Urothelial Carcinoma; Solid Tumor, Adult; Appendix Cancer; Esophagus Cancer
• Intervention / Treatment: Drug: CBX-12

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.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale Cancer Center
  • Texas
    • Austin, Texas, United States, 78758
      • NEXT Oncology
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

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 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
Experimental: Phase 2 Ovarian Cancer Expansion Cohort; CBX-12 administered TBD	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 Metastatic Breast Expansion Cohort; CBX-12 administered TBD	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 2: Overall response rate (ORR)	ORR Based on RECIST v1.1	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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Cybrexa Therapeutics
• Investigators: Study Director: Chief Medical Officer, Cybrexa Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2021
• Primary Completion (Actual): June 24, 2025
• Study Completion (Actual): June 24, 2025

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: May 21, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; breast; colorectal; ovarian; Sarcoma; small cell lung cancer; pancreatic; SCLC; appendix
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Esophageal Diseases; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms, Connective and Soft Tissue; Ovarian Neoplasms; Cecal Neoplasms; Cecal Diseases; Skin and Connective Tissue Diseases; Carcinoma, Ovarian Epithelial; Stomach Neoplasms; Colorectal Neoplasms; Esophageal Neoplasms; Breast Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Sarcoma; Carcinoma, Transitional Cell; Appendiceal Neoplasms
• Other Study ID Numbers: CBX-12-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No