NCT04902872

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.

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
130

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started May 2021

Longer than P75 for phase_1

Geographic Reach
1 country

4 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 3, 2021

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

May 21, 2021

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 26, 2021

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2025

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2025

Completed
Last Updated

January 23, 2025

Status Verified

January 1, 2025

Enrollment Period

3.8 years

First QC Date

May 21, 2021

Last Update Submit

January 21, 2025

Conditions

Solid Tumor, AdultEpithelial Ovarian CancerSmall Cell Lung CarcinomaBreast CancerColorectal CancerPancreas CancerAppendix CancerNon-small Cell Lung CancerGastric CancerEsophagus CancerUrothelial CarcinomaSarcoma

Keywords

SCLCsmall cell lung cancerovarianbreastappendixcolorectalpancreaticNSCLCSarcoma

Outcome Measures

Primary Outcomes (5)

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

    NCI CTCAE v5.0

    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)

    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)

    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)

    Safety Review Committee Analysis of Safety and PK Data

    15 months

  • Phase 2: Overall response rate (ORR)

    ORR Based on RECIST v1.1

    Through the end of study, estimated as 6 months

Secondary Outcomes (10)

  • Maximum concentration of CBX-12

    5 days

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

    5 days

  • Time to maximum concentration of CBX-12

    5 days

  • Half-life of CBX-12

    5 days

  • Clearance (CL) of CBX-12

    5 days

  • +5 more secondary outcomes

Study Arms (6)

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

EXPERIMENTAL

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

Drug: CBX-12

Phase 1 Schedule C Dose Escalation (Once Weekly Dosing )

EXPERIMENTAL

CBX-12 administered once weekly, 4 week schedule

Drug: CBX-12

Phase 2 Ovarian Cancer Expansion Cohort

EXPERIMENTAL

CBX-12 administered TBD

Drug: CBX-12

Phase 2 Metastatic Breast Expansion Cohort

EXPERIMENTAL

CBX-12 administered TBD

Drug: CBX-12

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

EXPERIMENTAL

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

Drug: CBX-12

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

EXPERIMENTAL

CBX-12 administered once every 3 weeks

Drug: CBX-12

Interventions

CBX-12DRUG

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

Phase 1 Modified Schedule B Dose Escalation (Once Every 3 weeks)Phase 1 Schedule A Dose Escalation (Daily Dosing x 5)Phase 1 Schedule B Dose Escalation (Daily Dosing x 3)Phase 1 Schedule C Dose Escalation (Once Weekly Dosing )Phase 2 Metastatic Breast Expansion CohortPhase 2 Ovarian Cancer Expansion Cohort

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Yale Cancer Center

New Haven, Connecticut, 06511, United States

Location

NEXT Oncology

Austin, Texas, 78758, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Carcinoma, Ovarian EpithelialSmall Cell Lung CarcinomaBreast NeoplasmsColorectal NeoplasmsPancreatic NeoplasmsAppendiceal NeoplasmsCarcinoma, Non-Small-Cell LungStomach NeoplasmsEsophageal NeoplasmsCarcinoma, Transitional CellSarcoma

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsOvarian NeoplasmsEndocrine Gland NeoplasmsNeoplasms by SiteOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesPancreatic DiseasesCecal NeoplasmsCecal DiseasesStomach DiseasesHead and Neck NeoplasmsEsophageal DiseasesNeoplasms, Connective and Soft Tissue

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 21, 2021

First Posted

May 26, 2021

Study Start

May 3, 2021

Primary Completion

March 1, 2025

Study Completion

June 1, 2025

Last Updated

January 23, 2025

Record last verified: 2025-01

Data Sharing

IPD Sharing
Will not share

Locations

US(4)