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

January 15, 2024 updated by: Cybrexa Therapeutics

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

Active, not recruiting

Conditions

Intervention / Treatment

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 (Estimated)

130

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Contact

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

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.

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

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

How is the study designed?

Design Details

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

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)
Time Frame: Through the end of study, estimated as 6 months
NCI CTCAE v5.0
Through the end of study, estimated as 6 months
Phase 2: Overall response rate (ORR)
Time Frame: Through the end of study, estimated as 6 months
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)
Time Frame: 15 months
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)
Time Frame: 15 months
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)
Time Frame: 15 months
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
Time Frame: 5 days
PK Analysis
5 days
Area under the curve from 0-24 hours of CBX-12
Time Frame: 5 days
PK Analysis
5 days
Time to maximum concentration of CBX-12
Time Frame: 5 days
PK Analysis
5 days
Half-life of CBX-12
Time Frame: 5 days
PK Analysis
5 days
Clearance (CL) of CBX-12
Time Frame: 5 days
PK Analysis
5 days
Apparent Volume of Distribution at Steady State (Vss) CBX-12
Time Frame: 5 days
PK Analysis
5 days
Phase 1: ORR
Time Frame: Through the end of study, estimated as 6 months
Based on RECIST v1.1
Through the end of study, estimated as 6 months
Duration of Response (DoR)
Time Frame: Through the end of study, estimated as 6 months
Based on RECIST v1.1
Through the end of study, estimated as 6 months
Progression-free Survival (PFS)
Time Frame: Through the end of study, estimated as 6 months
Based on RECIST v1.1
Through the end of study, estimated as 6 months
Phase 2: Incidence of TEAEs
Time Frame: Through the end of study, estimated as 6 months
NCI CTCAE v5.0
Through the end of study, estimated as 6 months

Collaborators and Investigators

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

Sponsor

Cybrexa Therapeutics

Investigators

  • Study Director: Chief Medical Officer, Cybrexa Therapeutics

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 Major Dates

Study Start (Actual)

May 3, 2021

Primary Completion (Estimated)

May 1, 2024

Study Completion (Estimated)

September 1, 2024

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)

January 17, 2024

Last Update Submitted That Met QC Criteria

January 15, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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