Clinical trial NCT04902872: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Cybrexa Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-05-26
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

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 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.

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.

Primary outcomes:
measure: Phase 1: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Through the end of study, estimated as 6 months
measure: Phase 1: Recommended Phase 2 Dose for Daily x 3 every 3 weeks schedule of CBX-12 (Schedule B)
timeFrame: 15 months
measure: Phase 1: Recommended Phase 2 Dose for Once Weekly schedule of CBX-12 (Schedule C)
timeFrame: 15 months
measure: Phase 1: Recommended Phase 2 Dose for Once Every 3 Weeks schedule of CBX-12 (Modified Schedule B)
timeFrame: 15 months
measure: Phase 2: Overall response rate (ORR)
timeFrame: Through the end of study, estimated as 6 months
Secondary outcomes:
measure: Maximum concentration of CBX-12
timeFrame: 5 days
measure: Area under the curve from 0-24 hours of CBX-12
timeFrame: 5 days
measure: Time to maximum concentration of CBX-12
timeFrame: 5 days
measure: Half-life of CBX-12
timeFrame: 5 days
measure: Clearance (CL) of CBX-12
timeFrame: 5 days
measure: Apparent Volume of Distribution at Steady State (Vss) CBX-12
timeFrame: 5 days
measure: Phase 1: ORR
timeFrame: Through the end of study, estimated as 6 months
measure: Duration of Response (DoR)
timeFrame: Through the end of study, estimated as 6 months
measure: Progression-free Survival (PFS)
timeFrame: Through the end of study, estimated as 6 months
measure: Phase 2: Incidence of TEAEs
timeFrame: Through the end of study, estimated as 6 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Austin
country: United States
facility: NEXT Oncology
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
References: