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Completed

NCT Number: NCT04902872

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.

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Key information

Conditions

Solid Tumor, Adult Adnexal Diseases Appendiceal Neoplasms Appendix Cancer Breast Cancer Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Carcinoma, Ovarian Epithelial Carcinoma, Transitional Cell Cecal Diseases Cecal Neoplasms Colonic Diseases Colorectal Cancer Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Epithelial Ovarian Cancer Esophageal Diseases Esophageal Neoplasms Esophagus Cancer Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastric Cancer Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Neoplasms Intestinal Diseases Intestinal Neoplasms Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Connective and Soft Tissue Neoplasms, Glandular and Epithelial Non-small Cell Lung Cancer Ovarian Diseases Ovarian Neoplasms Pancreas Cancer Pancreatic Diseases Pancreatic Neoplasms Rectal Diseases Respiratory Tract Diseases Respiratory Tract Neoplasms Sarcoma Skin Diseases Skin and Connective Tissue Diseases Small Cell Lung Carcinoma Stomach Diseases Stomach Neoplasms Thoracic Neoplasms Urogenital Diseases Urogenital Neoplasms Urothelial Carcinoma

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Yale Cancer Center, New Haven, Connecticut, United States

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

CBX-12

Drug

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 outcomes

  1. Phase 1: Incidence of treatment-emergent adverse events (TEAEs)

    Time frame: Through the end of study, estimated as 6 months

    NCI CTCAE v5.0

  2. 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

  3. 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

  4. 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

  5. Phase 2: Overall response rate (ORR)

    Time frame: Through the end of study, estimated as 6 months

    ORR Based on RECIST v1.1

Secondary outcomes

  1. Maximum concentration of CBX-12

    Time frame: 5 days

    PK Analysis

  2. Area under the curve from 0-24 hours of CBX-12

    Time frame: 5 days

    PK Analysis

  3. Time to maximum concentration of CBX-12

    Time frame: 5 days

    PK Analysis

  4. Half-life of CBX-12

    Time frame: 5 days

    PK Analysis

  5. Clearance (CL) of CBX-12

    Time frame: 5 days

    PK Analysis

  6. Apparent Volume of Distribution at Steady State (Vss) CBX-12

    Time frame: 5 days

    PK Analysis

  7. Phase 1: ORR

    Time frame: Through the end of study, estimated as 6 months

    Based on RECIST v1.1

  8. Duration of Response (DoR)

    Time frame: Through the end of study, estimated as 6 months

    Based on RECIST v1.1

  9. Progression-free Survival (PFS)

    Time frame: Through the end of study, estimated as 6 months

    Based on RECIST v1.1

  10. Phase 2: Incidence of TEAEs

    Time frame: Through the end of study, estimated as 6 months

    NCI CTCAE v5.0

Sponsors and collaborators

Lead sponsor

Cybrexa Therapeutics

Industry

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2025
Study completion
2025
First posted
May 26, 2021
Registry last updated
May 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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