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

Primary Purpose

Solid Tumor, Adult, Epithelial Ovarian Cancer, Small Cell Lung Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CBX-12
Sponsored by
Cybrexa Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor, Adult focused on measuring SCLC, small cell lung cancer, ovarian, breast, appendix, colorectal, pancreatic, NSCLC, Sarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Yale Cancer CenterRecruiting
  • NEXT Oncology
  • MD Anderson Cancer CenterRecruiting
  • NEXT OncologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Phase 1 Schedule B Dose Escalation (Daily Dosing x 3)

Phase 1 Schedule C Dose Escalation (Once Weekly Dosing )

Phase 2 Ovarian Cancer Expansion Cohort

Phase 2 Metastatic Breast Expansion Cohort

Phase 1 Schedule A Dose Escalation (Daily Dosing x 5)

Phase 1 Modified Schedule B Dose Escalation (Once Every 3 weeks)

Arm Description

CBX-12 administered on a daily x 3, 3 week schedule

CBX-12 administered once weekly, 4 week schedule

CBX-12 administered once every 3 weeks

CBX-12 administered once every 3 weeks

CBX-12 administered on a daily x 5, 3 week schedule

CBX-12 administered once every 3 weeks

Outcomes

Primary Outcome Measures

Phase 1: Incidence of treatment-emergent adverse events (TEAEs)
NCI CTCAE v5.0
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
Phase 1: Recommended Phase 2 Dose for Once Weekly schedule of CBX-12 (Schedule C)
Safety Review Committee Analysis of Safety and PK Data
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
Phase 2: Overall response rate (ORR)
ORR Based on RECIST v1.1

Secondary Outcome Measures

Maximum concentration of CBX-12
PK Analysis
Area under the curve from 0-24 hours of CBX-12
PK Analysis
Time to maximum concentration of CBX-12
PK Analysis
Half-life of CBX-12
PK Analysis
Clearance (CL) of CBX-12
PK Analysis
Apparent Volume of Distribution at Steady State (Vss) CBX-12
PK Analysis
Phase 1: ORR
Based on RECIST v1.1
Duration of Response (DoR)
Based on RECIST v1.1
Progression-free Survival (PFS)
Based on RECIST v1.1
Phase 2: Incidence of TEAEs
NCI CTCAE v5.0

Full Information

First Posted
May 21, 2021
Last Updated
April 13, 2023
Sponsor
Cybrexa Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT04902872
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 3, 2021 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
April 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cybrexa Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
SCLC, small cell lung cancer, ovarian, breast, appendix, colorectal, pancreatic, NSCLC, Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Parts B, C & Modified Part B 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 & Modified 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)
Allocation
Non-Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 Schedule B Dose Escalation (Daily Dosing x 3)
Arm Type
Experimental
Arm Description
CBX-12 administered on a daily x 3, 3 week schedule
Arm Title
Phase 1 Schedule C Dose Escalation (Once Weekly Dosing )
Arm Type
Experimental
Arm Description
CBX-12 administered once weekly, 4 week schedule
Arm Title
Phase 2 Ovarian Cancer Expansion Cohort
Arm Type
Experimental
Arm Description
CBX-12 administered once every 3 weeks
Arm Title
Phase 2 Metastatic Breast Expansion Cohort
Arm Type
Experimental
Arm Description
CBX-12 administered once every 3 weeks
Arm Title
Phase 1 Schedule A Dose Escalation (Daily Dosing x 5)
Arm Type
Experimental
Arm Description
CBX-12 administered on a daily x 5, 3 week schedule
Arm Title
Phase 1 Modified Schedule B Dose Escalation (Once Every 3 weeks)
Arm Type
Experimental
Arm Description
CBX-12 administered once every 3 weeks
Intervention Type
Drug
Intervention Name(s)
CBX-12
Intervention Description
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 Measure Information:
Title
Phase 1: Incidence of treatment-emergent adverse events (TEAEs)
Description
NCI CTCAE v5.0
Time Frame
Through the end of study, estimated as 6 months
Title
Phase 1: Recommended Phase 2 Dose for Daily x 3 every 3 weeks schedule of CBX-12 (Schedule B)
Description
Safety Review Committee Analysis of Safety and PK Data
Time Frame
15 months
Title
Phase 1: Recommended Phase 2 Dose for Once Weekly schedule of CBX-12 (Schedule C)
Description
Safety Review Committee Analysis of Safety and PK Data
Time Frame
15 months
Title
Phase 1: Recommended Phase 2 Dose for Once Every 3 Weeks schedule of CBX-12 (Modified Schedule B)
Description
Safety Review Committee Analysis of Safety and PK Data
Time Frame
15 months
Title
Phase 2: Overall response rate (ORR)
Description
ORR Based on RECIST v1.1
Time Frame
Through the end of study, estimated as 6 months
Secondary Outcome Measure Information:
Title
Maximum concentration of CBX-12
Description
PK Analysis
Time Frame
5 days
Title
Area under the curve from 0-24 hours of CBX-12
Description
PK Analysis
Time Frame
5 days
Title
Time to maximum concentration of CBX-12
Description
PK Analysis
Time Frame
5 days
Title
Half-life of CBX-12
Description
PK Analysis
Time Frame
5 days
Title
Clearance (CL) of CBX-12
Description
PK Analysis
Time Frame
5 days
Title
Apparent Volume of Distribution at Steady State (Vss) CBX-12
Description
PK Analysis
Time Frame
5 days
Title
Phase 1: ORR
Description
Based on RECIST v1.1
Time Frame
Through the end of study, estimated as 6 months
Title
Duration of Response (DoR)
Description
Based on RECIST v1.1
Time Frame
Through the end of study, estimated as 6 months
Title
Progression-free Survival (PFS)
Description
Based on RECIST v1.1
Time Frame
Through the end of study, estimated as 6 months
Title
Phase 2: Incidence of TEAEs
Description
NCI CTCAE v5.0
Time Frame
Through the end of study, estimated as 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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. (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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Operations Trial Team
Phone
860-717-2731
Email
clinicalstudies@cybrexa.com
Facility Information:
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ingrid Palma
Phone
203-833-1034
Email
ingrid.palma@yale.edu
First Name & Middle Initial & Last Name & Degree
Patricia LoRusso, MD
Facility Name
NEXT Oncology
City
Austin
State/Province
Texas
ZIP/Postal Code
78758
Country
United States
Individual Site Status
Completed
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Tjarks
Phone
713-689-4523
Email
JJTjarks@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Funda Meric-Bernstam, MD
Facility Name
NEXT Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cynthia De Leon
Phone
210-580-9521
Email
cdeleon@nextoncology.com
First Name & Middle Initial & Last Name & Degree
Anthony Tolcher, MD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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