First-in-Class Bispecific Antibody, ALG.APV-527, Meets Important Trial Endpoints in Phase 1 Solid Tumor Trial
APVO 11.11.2024
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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
"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.
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 monthsThe 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
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About Alligator Bioscience
Alligator Bioscience AB is a clinical-stage biotechnology company developing tumor-directed immuno-oncology antibody drugs. Alligator's portfolio includes several promising drug candidates, with the CD40 agonist mitazalimab as its key asset. Furthermore, Alligator is co-developing ALG.APV-527 with
Alligator Bioscience's shares are listed on Nasdaq Stockholm (ATORX) and is headquartered in
For additional information, please contact:
Alligator BioscienceCorporate
Søren Bregenholt, CEOsoren.bregenholt@alligatorbioscience.com+46 46-540 82 00
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This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, including, without limitation, Aptevo's expectations about the activity, efficacy, safety, tolerability and durability of its therapeutic candidates and potential use of any such candidates, including in combination with other drugs, as therapeutics for treatment of disease, its expectations regarding the effectiveness of its ADAPTIR and ADAPTIR-FLEX platforms, statements related to the progress of Aptevo's clinical programs, including statements related to anticipated clinical and regulatory milestones, whether further study of mipletamig in a Phase 1b dose optimization trial focusing on multiple doses of mipletamig in combination with venetoclax + azacitidine on a targeted patient population will continue to show clinical benefit, whether Aptevo's final trial results will vary from its earlier assessment, whether further study of ALG.APV-527 across multiple tumor types will continue to show clinical benefit, whether higher dose ranges for ALG.APV-527 will result in increased signs of clinical activity, whether biomarker analyses will continue to confirm biological activity of ALG.APV-527, the possibility and timing of future preliminary or interim data readouts for ALG.APV-527, whether Aptevo's final trial results will vary from its preliminary or interim assessments, statements related to the progress of and enthusiasm for Aptevo's clinical programs, statements related to Aptevo's ability to generate stockholder value, whether Aptevo will continue to have momentum in its business in the future, and any other statements containing the words "may," "continue to," "believes," "knows," "expects," "optimism," "potential," "designed," "promising," "plans," "will" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based on Aptevo's current intentions, beliefs, and expectations regarding future events. Aptevo cannot guarantee that any forward-looking statement will be accurate. Investors should realize that if underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could differ materially from Aptevo's expectations. Investors are, therefore, cautioned not to place undue reliance on any forward-looking statement.
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