At this stage in Pendrea’s development the clinical program revolves around the testing of our lead product, Ceraxa. A summary of Ceraxa’s Phase 1 results and Phase 2 clinical trial strategies for Solid Tumors and AML is provided below.
Ceraxa -- Phase 1 Clinical Trial Results
A recently completed Phase 1 clinical trial of Ceraxa as a monotherapy in Solid Tumors achieved its goal of confirming initial safety and pharmacokinetics in a multi-dose escalation study. In this trial:
Patients received an average of 20 doses, with a maximum of 48 doses
No Significant Adverse Events (SAEs) were observed
No Dose Limiting Toxicities (DLTs) were observed
A Maximum Tolerated Dose (MTD) was not reached
All patients were stage 4, had metastatic disease and had failed all previous treatments.
The study was conducted at the University of Maryland Greenebaum Cancer Center, the University of Virginia Emily Couric Cancer Center and the Medical University of South Carolina Hollings Cancer Center. The trial was partially paid for by a $2 million grant from the National Cancer Institute.
An early efficacy signal was detected in the dose range predicted from numerous preclinical studies -- 5 patients out of 13 (38.5%) experienced stable disease for up to 24 weeks with mixed tumor responses including tumor reductions. A total of 10 different solid tumor types were enrolled in the study with stable disease observed in breast (2), pancreatic, lung and salivary gland cancers.
Because Ceraxa is being developed to synergize with approved standard of care chemotherapeutics, the efficacy signal as a single agent was not anticipated in this monotherapy safety study and is considered a very encouraging sign for the use of Ceraxa in combination with Standard of Care therapeutics. Furthermore, the confirmation of Ceraxa’s excellent safety profile in the trial means that it can be added to Standard of Care treatments to restore and/or increase the efficacy of those treatments without adding side effects. This provides Ceraxa with a wide range of opportunities to improve the activity of existing Standard of Care therapeutics in any number of product combinations and indications.
Ceraxa -- Clinical Strategy -- Restoration of efficacy to existing chemotherapeutics for Relapsed & Refractory Patients
It is Pendrea’s premise that Ceraxa will be synergistic with a number of anti-neoplastic agents, and that it can restore and/or improve efficacy in a wide range of malignancies when added to currently approved therapeutics. The cancer types and drugs against which Ceraxa will be tested have been chosen on the basis of promising preclinical evidence of synergy between Ceraxa and the standard of care therapy for the indication. In all cases, Ceraxa’s distinctly different mechanism of action not only kills cancer cells while not affecting healthy cells, but also sensitizes cancer cells to chemotherapy resulting in a synergistic effect that does not add toxicity.
Solid Tumors Phase 2 Clinical Trial
Pendrea is preparing to test Ceraxa in a Phase 2 clinical trial in combination with approved chemotherapeutic agents in multiple solid tumor indications. The objective of the trial will be to demonstrate that the combination of Ceraxa with chemotherapeutic agents known to be synergistic with Ceraxa will result in anti-tumor efficacy in patients who are not responding to the current standard of care. Ceraxa’s ability to restore activity in this patient population without adding further side effects fills a critical unmet need while requiring a relatively low Overall Response Rate (ORR) of only 20% and a limited number of patients to be approvable. The trial design and target patient population provide a rapid and efficient regulatory path to approval. Pendrea expects the Phase II efficacy trial to be completed within two years, and at a relatively low cost.
The Phase 2 Solid Tumors Combination Therapy trial uses an “adaptive” trial design that tests multiple indications in small baskets to determine the preliminary efficacy of different Ceraxa combination therapies in multiple cancers. The best responding cancer will then be tested for confirmation of efficacy.
AML Phase 2 Clinical Trial
The AML trial starts with a monotherapy dose ranging study to confirm safety and immediately moves to testing of Ceraxa in combination with a current standard of care treatment, Venetoclax and AraC in relapsed and refractory patients. The Phase 2 trial will also include an arm for testing of Ceraxa in combination with Vinblastine, which is a novel treatment approach since Vinblastine is not currently used for treatment of AML. The Phase 2 for AML will test is expected to take three years to complete.
Building off the premise that Ceraxa does not change the safety profile for the combination therapies being tested, the demonstration of efficacy in the setting of relapsed and/or refractory disease should result in a strong recommendation for accelerated approval and/or breakthrough drug status for Ceraxa.