alphalex-exatecan (CBX-12) / Cybrexa Therap - LARVOL DELTA

CBX-12-101: A first-in-human study of CBX-12, an alphalex peptide drug conjugate (PDC) in patients (pts) with advanced or metastatic solid tumors. (ASCO 2023) - P1/2 | "In this FIH study of a pH-targeting alphalex PDC, CBX-12 demonstrated single-agent antitumor activity including 4 responses with the dominant toxicity of myelosuppression. Phase 2 expansion cohorts are planned in pts with platinum-resistant ovarian cancer and hormone-receptor positive, HER2 negative breast cancer. Clinical trial information: NCT04902872."

Clinical • Metastases • P1 data • Anemia • Breast Cancer • Fatigue • Febrile Neutropenia • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Infectious Disease • Neutropenia • Oncology • Ovarian Cancer • Septic Shock • Solid Tumor • Thrombocytopenia • HER-2 • TOP1

A Phase 1/2 Study of CBX-12 in Children, Adolescents, or Young Adults With Solid Tumors That Have Come Back After Treatment or Are Difficult to Treat (clinicaltrials.gov) - P1/2 | N=79 | Not yet recruiting | Sponsor: Children's Oncology Group

New P1/2 trial • Ewing Sarcoma • Oncology • Pediatrics • Rhabdomyosarcoma • Sarcoma • Solid Tumor

A Study of CBX 12 in Subjects With Platinum Resistant or Refractory Ovarian Cancer (clinicaltrials.gov) - P2 | N=40 | Terminated | Sponsor: Cybrexa Therapeutics | Recruiting ➔ Terminated; Limited clinical activity

Platinum resistant • Trial termination • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Refractory Ovarian Cancer • Solid Tumor

CBX-12-101: Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=69 | Completed | Sponsor: Cybrexa Therapeutics | Active, not recruiting ➔ Completed | N=130 ➔ 69 | Trial primary completion date: Mar 2025 ➔ Jun 2025

Enrollment change • First-in-human • Trial completion • Trial primary completion date • Appendix Cancer • Breast Cancer • Colorectal Cancer • Epithelial Ovarian Cancer • Esophageal Cancer • Gastric Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Urothelial Cancer

Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers (clinicaltrials.gov) - P1 | N=35 | Recruiting | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor • RAD51 • TOP1

Phase 2 trial of CBX-12 for metastatic chemotherapy-refractory microsatellite stable colorectal cancer (ETCTN 10707). (ASCO-GI 2026) - P2 | "The trial opened to enrollment on 8/21/25. NCT06730100."

Metastases • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • SLFN11 • TOP1

PRECLINICAL EFFICACY OF A PH-SENSITIVE EXATECAN PEPTIDE-DRUG-CONJUGATE IN RHABDOMYOSARCOMA (CTOS 2025) - "CBX-12 (alphalex™ exatecan) is a pHLIP-based conjugate that selectively delivers exatecan to tumors... Preclinical data demonstrate CBX‑12's potent activity in RMS models, with excellent tolerability. Combined with Phase I adult data showing tumor responses and manageable safety, these findings strongly support further clinical development in pediatric RMS."

Preclinical • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • FOXO1

Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor • RAD51 • TOP1

Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers (clinicaltrials.gov) - P1 | N=35 | Suspended | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Suspended

Trial suspension • Oncology • Solid Tumor • RAD51 • TOP1

A Study of CBX 12 in Subjects With Platinum Resistant or Refractory Ovarian Cancer (clinicaltrials.gov) - P2 | N=40 | Recruiting | Sponsor: Cybrexa Therapeutics | N=60 ➔ 40 | Trial completion date: Jul 2026 ➔ Oct 2025 | Trial primary completion date: Apr 2026 ➔ Oct 2025

Enrollment change • Platinum resistant • Trial completion date • Trial primary completion date • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor

CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: National Cancer Institute (NCI) | N=35 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Colorectal Cancer • Oncology • Solid Tumor

Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers (clinicaltrials.gov) - P1 | N=35 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor • RAD51 • TOP1

CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer (clinicaltrials.gov) - P2 | N=35 | Recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor

Peptide-Drug Conjugates: A New Hope for Cancer. (PubMed, J Pept Sci) - "Only Lutathera remains FDA-approved after Pepaxto's withdrawal, though Pepaxto retains EMA and MHRA approval-highlighting regulatory and technical complexities. Most PDCs target overexpressed receptors (e.g., somatostatin and GnRH), though novel designs like CBX-12 employ alternative strategies...Promising candidates in late-stage trials are highlighted, emphasising their potential to address unmet needs in oncology. By refining targeting precision and payload delivery, next-generation PDCs may expand treatment options for resistant cancers, bridging the gap between biologics and small-molecule therapies."

Journal • Review • Oncology

CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer (clinicaltrials.gov) - P2 | N=35 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

Trial suspension • Colorectal Cancer • Oncology • Solid Tumor

CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer (clinicaltrials.gov) - P2 | N=35 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2026 ➔ Dec 2026 | Initiation date: May 2025 ➔ Feb 2026 | Trial primary completion date: Jun 2026 ➔ Dec 2026

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor

CBX-12-101: Study of CBX-12 in Subjects with Advanced or Metastatic Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=130 | Active, not recruiting | Sponsor: Cybrexa Therapeutics | Trial completion date: Mar 2025 ➔ Jun 2025

Trial completion date • Appendix Cancer • Breast Cancer • Colorectal Cancer • Epithelial Ovarian Cancer • Esophageal Cancer • Gastric Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Urothelial Cancer

CBX-12 for the Treatment of Metastatic Chemotherapy-Refractory Microsatellite Stable Colorectal Cancer (clinicaltrials.gov) - P2 | N=35 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

Metastases • New P2 trial • Colorectal Cancer • Oncology • Solid Tumor • SLFN11 • TOP1

Cybrexa Therapeutics Announces First Patient Dosed with First-in-Class Peptide-Drug Conjugate CBX-12 in Phase 2 Trial in Ovarian Cancer (GlobeNewswire) - "Cybrexa Therapeutics...announced that the first patient has been dosed in a Phase 2 clinical trial evaluating CBX-12 in patients with platinum-resistant or refractory ovarian cancer....Cybrexa plans an additional Phase 2 study of CBX-12 in colorectal cancer in 2025 in collaboration with the National Cancer Institute (NCI), as well as other Phase 2 studies evaluating CBX-12 as a monotherapy and in combination across a range of solid tumors."

New P2 trial • Trial status • Colorectal Cancer • Ovarian Cancer • Solid Tumor

CBX-12-101: Final results of a phase I study of CBX-12, a peptide drug conjugate (PDC) in patients (pts) with metastatic solid tumors (ESMO 2024) - P1/2 | "Tumor targeting facilitated by this pH sensitive peptide made possible an improved safety profile despite the administration of a 5-fold increase in the dose of exatecan compared to unconjugated exatecan. The dose limiting toxicity is myelosuppression. CBX-12 demonstrated broad activity with 5 confirmed responses in three malignancies."

Clinical • Metastases • P1 data • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thymus Cancer

Cybrexa Therapeutics Announces Positive Final Data at ESMO 2024 from Phase 1 Study of Peptide Drug Conjugate CBX-12 in Advanced Solid Tumors (GlobeNewswire) - P1/2 | N=130 | NCT04902872 | Sponsor: Cybrexa Therapeutics | "Specifically, in 10 ovarian cancer patients who were TOP1-naïve, there was one confirmed complete response, one confirmed partial response (PR), and two unconfirmed PRs, with eight out of 12 patients showing clinical benefit. In seven TOP1-naïve breast cancer patients, there were two confirmed PRs and one unconfirmed PR. All evaluable breast participants were HER-2 negative and HR positive....The PK of CBX-12 and exatecan exhibited linear dose-proportional behavior, with a mean half-life ranging from 14 to 22 hours across the dose range studied....An additional Phase 2 study in colorectal cancer is planned for 2025 in collaboration with the National Cancer Institute (NCI), as well as other Phase 2 studies in solid tumors as a monotherapy and in combination."

New P2 trial • P1 data • PK/PD data • Breast Cancer • Colorectal Cancer • Gallbladder Cancer • Gastrointestinal Cancer • Gynecologic Cancers • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thymic Carcinoma

A Study of CBX 12 in Subjects With Platinum Resistant or Refractory Ovarian Cancer (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Cybrexa Therapeutics | Trial completion date: Apr 2026 ➔ Jul 2026 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial completion date • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor

CBX-12-101: Study of CBX-12 in Subjects With Advanced or Metastatic Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=130 | Active, not recruiting | Sponsor: Cybrexa Therapeutics | Trial completion date: Sep 2024 ➔ Mar 2025 | Trial primary completion date: May 2024 ➔ Jan 2025

Metastases • Trial completion date • Trial primary completion date • Appendix Cancer • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Urothelial Cancer

Pilot study of CBX-12 pharmacodynamics in patients with advanced solid tumors. (ASCO 2024) - P1, P1/2 | "Mandatory biopsies will be collected at baseline, 24-36 hours post first dose, and on cycle 3 day 1 to assess both short- and long-term effects of CBX-12 on the tumor. Mandatory research blood samples will be collected at specified timepoints for pharmacokinetic, circulating tumor cell, and cell-free DNA analyses."

Clinical • Metastases • PK/PD data • Hematological Disorders • Neutropenia • Oncology • Ovarian Cancer • Solid Tumor • CD8 • TOP1

Testing How the Body Responds to the Drug CBX-12 in Patients With Advanced Solid Cancers (clinicaltrials.gov) - P1 | N=35 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2025 ➔ Oct 2026 | Trial primary completion date: Mar 2025 ➔ Oct 2026

Enrollment open • Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • RAD51