ALG.APV-527 shows initial promise in solid tumors, including GU cancers

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Preliminary data showed that the treatment was well-tolerated, and a maximum tolerated dose had not yet been reached.

The bispecific conditional 4-1BB agonist ALG.APV-527 has demonstrated tolerability and preliminary efficacy in patients with advanced solid tumors, according to initial data from a phase 1 dose escalation study (NCT05934539)of the therapy in solid tumors likely to express the tumor antigen 5T4, including renal cell carcinoma (RCC), urothelial carcinoma, and prostate cancer.

Following the dose escalation portion of the study, the investigators will further assess the safety and clinical activity of ALG.APV-527 in a phase 2 study of up to 20 patients with advanced solid tumors.

Interim findings from the study were shared in a joint news release by Alligator Bioscience and Aptevo Therapeutics, the co-developers of the therapy.¹

At the time of data report, the multicenter trial had reached over 50% enrollment. Preliminary data showed that the treatment was well-tolerated, and a maximum tolerated dose had not yet been reached. Dose escalation in higher-dose cohorts remain ongoing.
Additionally, results showed that ALG.APV-527 could be measured in all patients with a plasma concentration of ALG.APV-527 consistent with the administered dose. Biomarker analyses also confirmed the biological activity of ALG.APV-527 by demonstrating the expression of the targets (4-1BB and 5T4) in tumor biopsies.

"We're thrilled to share positive interim phase 1 data from our trial with ALG.APV-527, a testament to our dedicated collaboration with Aptevo. The presence of both targets in tumor biopsies is a particularly encouraging finding, which underlines the potential of our novel bispecific antibody to treat multiple indications. We very much look forward to continuing this journey together to make a meaningful impact in the fight against cancer,” said Sumeet Ambarkhane, MD, the Chief Medical Officer at Alligator Bioscience, in the news release.¹

Overall, the open-label dose escalation study is assessing the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of ALG.APV-527 in adult patients with advanced solid tumors. The study will include patients across multiple solid tumor types likely to express the 5T4 antigen, including RCC, urothelial carcinoma, and prostate cancer, as well as non-small cell lung cancer, gastric/gastro-esophageal cancer, head and neck squamous cell carcinoma, ovarian cancer, breast cancer, malignant pleural mesothelioma, cervical cancer, colorectal cancer, endometrial cancer, and pancreatic cancer.²

Participants for the study will be enrolled across 10 clinical trial sites in the US and treated across 6 dosing cohorts. Each patient will receive ALG.APV-527 intravenously once every 2 weeks. Dose escalation will stop when at least 2 out of 3 or 6 patients experience dose limiting toxicities at that dose level.

"I am pleased to share that we are now dosing cohort 4, heading into higher dose ranges where we believe there is potential for increased signs of clinical activity based on preclinical models. We have treated patients with multiple tumor types including breast, pancreatic, non-small cell lung cancer, and colorectal cancer. It is our belief that continued analysis of this cross section of tumor types will offer important insights about ALG.APV-527 that can be used to increase our success in later stage development," said Dirk Huebner, MD, Chief Medical Officer at Aptevo, in the news release.¹ "Additionally, as the trial has progressed, we have seen growing enthusiasm among our clinical sites, evidenced by a long and growing waiting list of patients who would like to participate in the study. We look forward to announcing additional data later in the year."

References

1. Alligator Bioscience and Aptevo Therapeutics announce positive interim data of dose escalation phase of ALG.APV-527 phase 1 study in solid tumor cancers expressing tumor antigen 5T4. News release. Alligator Bioscience AB and Aptevo Therapeutics. March 7, 2024. Accessed March 11, 2024. https://www.accesswire.com/840039/alligator-bioscience-and-aptevo-therapeutics-announce-positive-interim-data-of-dose-escalation-phase-of-algapv-527-phase-1-study-in-solid-tumor-cancers-expressing-tumor-antigen-5t4

2. ALG.APV-527 first-in-human study. ClinicalTrials.gov. Last updated July 7, 2023. Accessed March 11, 2024. https://clinicaltrials.gov/study/NCT05934539