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

Sponsor

Cybrexa Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04902872

Collaborator

(none)

112

Enrollment

Locations

Arms

Anticipated Duration (Months)

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: CBX-12	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

112 participants

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.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

Official Title:

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

Actual Study Start Date :

May 3, 2021

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 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 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 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	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 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	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

Outcome Measures

Primary Outcome Measures

Phase 1: Incidence of treatment-emergent adverse events (TEAEs) [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 [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 [15 months]
Safety Review Committee Analysis of Safety and PK Data
Phase 2: Overall response rate (ORR) [Through the end of study, estimated as 6 months]
ORR Based on RECIST v1.1

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Cancer Center	New Haven	Connecticut	United States	06511
2	NEXT Oncology	Austin	Texas	United States	78758
3	MD Anderson Cancer Center	Houston	Texas	United States	77030
4	NEXT Oncology	San Antonio	Texas	United States	78229