Bifogade filer
First-in-Class Bispecific Antibody, ALG.APV-527, Meets Important Trial Endpoints in Phase 1 Solid Tumor Trial
Prenumeration
Beskrivning
| Land | Sverige |
|---|---|
| Lista | Small Cap Stockholm |
| Sektor | Hälsovård |
| Industri | Bioteknik |
Alligator Bioscience and Aptevo Therapeutics report favorable safety, tolerability and evidence of biological activity of ALG.APV-527, more than half of evaluable patients achieved stable disease.
- Colon cancer patient achieved stable disease and remained on study for more than six months, breast cancer patient remained on study for more than 11 months
- Biomarker analysis confirms immune activation in the tumor microenvironment
- Data Presented at Society for Immunotherapy of Cancer on November 8, 2024
LUND, SWEDEN and SEATTLE WA November 11, 2024, Alligator Bioscience AB ("Alligator") (ATORX) and Aptevo Therapeutics ("Aptevo") (Nasdaq: APVO) today announced preliminary data from the companies’ Phase 1 trial evaluating the first-in-class bispecific antibody, ALG.APV-527, as monotherapy for the treatment of multiple solid tumor types likely to express tumor antigen 5T4. These data indicate that trial endpoints of adequate exposure, safety, tolerability and biological activity were met. Outcomes were presented at a poster session on Friday, November 8, 2024, at the Society for Immunotherapy of Cancer Conference in Houston, Texas.
"The interim results from Phase 1 trials of ALG.APV-527 are showing encouraging outcomes, particularly in terms of safety and disease stability in the trial patients who were refractory to multiple previous therapies. Among evaluable patients, 56% (9/16) achieved stable disease in this monotherapy trial. A colon cancer patient remained on study with stable disease for more than six months as well as a breast cancer patient who remained stable for over 11 months. Importantly, there were no instances of serious liver toxicity, a notable outcome given the relatively high incidence of this side effect associated with other treatments targeting 4-1BB. By leveraging a novel bispecific approach, ALG.APV-527 aims to enhance anti-tumor immunity while avoiding the systemic toxicities that previously have hampered the 4-1BB immune receptor pathway. These findings underscore the drug’s potential as a viable option for patients with solid tumors," noted Dr. Thomas Marron, MD, PhD, Professor of Immunology & Immunotherapy and Hematology/Oncology at the Icahn School of Medicine at Mount Sinai, and a leading investigator in the trial.
Clinical Highlights
Safety and Tolerability
- ALG.APV-527 demonstrated positive safety and tolerability across all cohorts
- No serious liver toxicity, a common side effect of other 4-1BB targeting treatments that can cause patients to discontinue dosing, was observed
- A maximum tolerated dose has not been identified, highlighting the tolerability of the drug at high dose levels
Clinical Activity/Efficacy
- Nine of 16 efficacy evaluable patients (56%) achieved stable disease (SD)
- One colon cancer patient achieved SD for more than six months
- The longest SD duration was in a breast cancer patient who entered the study with progressive disease, achieved stable disease and remained on study for >11 months. This patient successfully transitioned to a higher dose level twice
Evidence of biological activity of ALG.APV-527
- ALG.APV-527 could be measured in all patients. Serum concentrations of ALG.APV-527 were proportional to the administered dose
- Analysis of biomarkers in the serum of treated patients including soluble 4-1BB (surface protein found on certain immune cells) confirm biological activity of ALG.APV-527
- Analysis of biomarkers in biopsies (including the 5T4 target cells and CD8 T cancer killer cells are consistent with immune activation in the tumor microenvironment). This observation consistent with ALG.APV-527 expected MOA.
About the Trial
The ALG.APV-527 Phase 1 trial is a multi-center, multi-cohort, open-label dose-escalation trial that includes administration of ALG.APV-527 in up to six escalating dose levels in a 3+3 design*. The trial is enrolling adult patients with multiple solid tumor types/histologies likely to express the 5T4 antigen. ALG.APV-527 will be given intravenously once every two weeks. The trial is assessing the safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ALG.APV-527.
*The 3+3 design proceeds in cohorts of three patients treated at increasing dose levels. Dose escalation stops when at least two out of three or six patients experience dose limiting toxicities (DLTs) at that dose level.
About ALG.APV-527
ALG.APV-527 is a bispecific conditional 4-1BB agonist, only active upon simultaneous binding to 4-1BB and 5T4. This has the potential to be clinically important because 4-1BB can stimulate the immune cells (antitumor-specific T cells and NK cells) involved in tumor control, making 4-1BB a particularly compelling target for cancer immunotherapy. 5T4 is an oncofetal tumor associated antigen overexpressed on numerous solid tumors including non-small-cell lung carcinoma (NSCLC), breast, head and neck, cervical, renal, gastric, and colorectal cancer.
Preclinical studies, highlighting the differentiated design of the molecule that minimizes systemic immune activation, allowing for highly efficacious tumor-specific responses as demonstrated by potent activity in preclinical models, has been published in the peer-reviewed publication, Molecular Cancer Therapeutics, a journal of the American Association for Cancer Research (AACR).