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

• ClinicalTrials.gov Identifier: NCT04902872
• Recruitment Status: Recruiting
• First Posted: May 26, 2021
• Last Update Posted: May 13, 2022
• Sponsor: Cybrexa Therapeutics
• Information provided by (Responsible Party): Cybrexa Therapeutics

Tracking Information

• First Submitted Date: May 21, 2021
• First Posted Date: May 26, 2021
• Last Update Posted Date: May 13, 2022
• Actual Study Start Date: May 3, 2021
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 9, 2022)

• Phase 1: Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Through the end of study, estimated as 6 months ]
  NCI CTCAE v5.0
• Phase 1: Recommended Phase 2 Dose for Daily x 3 every 3 weeks schedule of CBX-12 [ Time Frame: 15 months ]
  Safety Review Committee Analysis of Safety and PK Data each schedule in Part B and Part C
• Phase 1: Recommended Phase 2 Dose for Once Weekly schedule of CBX-12 [ Time Frame: 15 months ]
  Safety Review Committee Analysis of Safety and PK Data
• Phase 2: Overall response rate (ORR) [ Time Frame: Through the end of study, estimated as 6 months ]
  ORR Based on RECIST v1.1

Original Primary Outcome Measures (submitted: May 21, 2021)

• Phase 1: Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Through the end of study, estimated as 6 months ]
• Phase 1: Recommended Phase 2 Dose for Daily x 5 every 3 weeks schedule of CBX-12 [ Time Frame: 15 months ]
• Phase 1: Recommended Phase 2 Dose for Daily x 3 every 3 weeks schedule of CBX-12 [ Time Frame: 15 months ]
• Phase 2: Overall response rate (ORR) [ Time Frame: Through the end of study, estimated as 6 months ]
  Based on RECIST v1.1

Current Secondary Outcome Measures (submitted: May 9, 2022)

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

Original Secondary Outcome Measures (submitted: May 21, 2021)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors
• Official Title: A Phase 1/2 Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors
• 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 two 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.

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 both Part B and Part C, Phase 2 expansion cohorts may open.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Parts B and C will follow a 3 + 3 design, enrolling 3 subjects in each cohort. (De)escalation rules: DLT period for each subject in Phase 1 Part B will be 3 weeks & 4 weeks in Part C (i.e., 1 cycle). If none of the 3 subjects experience a DLT, dose will be escalated to next highest dose level. If 1 of 3 subjects in cohort experiences a DLT, up to 3 additional subjects will be enrolled/treated at same dose. If none of the additional 3 subjects experience a DLT (i.e., only 1 of 6 subjects in cohort has a DLT), dose will be escalated to next highest level. If 2 or more of up to 6 subjects at dose level have DLTs, enrollment to that cohort will stop, dose will be considered above MTD. Dose will be decreased to previous dose level or to a level intermediate to those previously evaluated. MTD will be highest dose evaluated at which ≤ 1 of 6 have a DLT. A minimum of 6 DLT-evaluable subjects will be enrolled to any dose level being evaluated as possible MTD.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• 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

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

Study Arms

• Experimental: Phase 1 Dose Escalation (Daily Dosing x 3)
  CBX-12 administered on a daily x 3, 3 week schedule
  Intervention: Drug: CBX-12
• Experimental: Phase 1 Dose Escalation (Once Weekly Dosing )
  CBX-12 administered once weekly, 4 week schedule
  Intervention: Drug: CBX-12
• Experimental: Phase 2 Ovarian Cancer Expansion Cohort
  CBX-12 administered on a daily x 5 every 3 weeks or on a daily x 3 every 3 weeks schedule
  Intervention: Drug: CBX-12
• Experimental: Phase 2 Small Cell Lung Cancer Expansion Cohort
  CBX-12 administered on a daily x 5 every 3 weeks or on a daily x 3 every 3 weeks schedule
  Intervention: Drug: CBX-12

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 21, 2021): 112
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 2024
• Estimated Primary Completion Date: January 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Project Manager; 860-501-3027; clinicalstudies@cybrexa.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04902872
• Other Study ID Numbers: CBX-12-101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cybrexa Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Cybrexa Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Chief Medical Officer; Cybrexa Therapeutics

• PRS Account: Cybrexa Therapeutics
• Verification Date: May 2022