Investigators successfully established the phase 2 dose of APVO436 for patients with acute myeloid leukemia or myelodysplastic syndrome after an acceptable safety profile was achieved in patients with responses to therapy.
Results of the phase 1 dose-escalation APTEVO study 5001 (NCT03647800) evaluating APVO436 in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) indicated a favorable safety profile with low rates of neutropenia, according to the company responsible for the drug candidate, Aptevo Therapeutics, Inc.
The bispecific antibody that targets both CD3 and CD123, of which overexpression is seen in many forms of leukemia, also showed encouraging single-agent activity and a promising benefit-to-risk profile in patients with advanced, relapsed AML. APVO436 was developed using ADAPTIR technology, which is used to produce highly differentiated bispecific and multi-specific antibodies across a wide range of mechanisms of action.
“We are very pleased to see lead ADAPTIR platform candidate, APVO436, progress in the clinic. APVO436 has demonstrated the potential to address a significant unmet need for patients with AML and provide the foundation for new and more effective multi-modality standard of care regimens that offer renewed hope for leukemia patients,” Jane Gross, PhD, Chief Scientific Officer for Aptevo, said in a press release.
In 7 evaluable patients with relapsed AML, 4 showed disease stabilization. Only 1 patient with initial disease stabilization progressed within 1 month, while the remaining 3 lived for 246+, 261+, and 281+ days, respectively. Two patients experienced a partial response to therapy and 1 subsequent complete response. Notably, no partial responses were noted above or below the recommended phase 2 dose.
Two of the most common adverse effects of therapy with APVO436 included neurologic toxicities and cytokine release syndrome (CRS). Out of 9 patients with AML or MDS, 2 developed grade 1 CRS and 1 had a transient grade 3 event.
Prolonged or severe neutropenia, a common issue with antileukemic therapies, was not noted at dose levels that resulted in a complete remission to therapy.
“This finding will inform the clinical development path for APVO436, as a novel drug candidate for blood cancers,” Fatih M. Uckun, MD, PhD, leukemia expert and Chief Clinical Advisor who is coordinating the APVO436 clinical development program, said in a press release. “AML patients are in urgent need of active new drugs capable of destroying leukemia cells without causing profound neutropenia. We will diligently advance the clinical development of APVO436 and evaluate its potential clinical impact for leukemia patients.”
Patients enrolled in the trial were recruited to 1 of 10 dose-escalation cohorts to determine the recommended phase 2 dose. Part 2 of the trial will evaluate the safety and efficacy of this dose as adjunctive therapy to the standard of care and to obtain a preliminary assessment of the anti-leukemia activity of APVO436-containing experimental monotherapy and combination therapy modalities. Target enrollment is 136 patients with relapsed/refractory AML or high-grade MDS.
To be eligible, patients must have an ECOG performance score of 2 or less, a life expectancy over 2 months, a white blood cell count lower than 25,000 cells/mm3, creatinine less than 2 times the upper limit of normal, adequate liver function tests, and a prothrombin time less than 1.5 times the upper limit of normal.
“We are pleased to report progress in the clinical development of our ADAPTIR platform candidate, APVO436,” Marvin White, President and CEO of Aptevo, said in the release. “We remain confident about the breakthrough potential of APVO436 and look forward to sharing interim data from Part 2 of our study later this year. The scientific data from multiple studies so far suggest tremendous therapeutic potential for the APVO436 ADAPTIR platform and provides the foundation for our optimism regarding the potential commercialization of APVO436.”
Aptevo Therapeutics Reports Positive Phase 1 Clinical Data for Its Lead Leukemia Drug Candidate APVO436 in Adults With Relapsed Acute Myeloid Leukemia. News release. Aptevo Therapeutics, Inc. May 26, 2021. Accessed May 27, 2021. https://bit.ly/2SBTxR2