New duration of remission data add to a growing body of clinical evidence supporting the development of APVO436 in combination therapy for patients with acute myeloid leukemia.
The combination of APVO436, venetoclax (Venclexta), and azacitidine, achieved positive duration of remission (DOR) results in the phase 1b dose-escalation trial (NCT03647800) for treatment naïve patients with acute myeloid leukemia (AML).1
In the study, there was an 82% high response rate observed with 9 of the 11 patients who had a favorable response eligible for inclusion in the DOR analysis. Multiple patients moved to transplant and 3 of the patients responded sufficiently to move to stem cell transplant, which was deemed the treatment option with the best probability for survival and highest benefit to patients.
Among the patients with responses, 1 remained in study with a sustained complete response for 8 cycles. This translated to at least 8 months of response duration. The median DOR was not reached. These data are clinically meaningful as a substantial number of patients stayed on treatment or moved to transplant. Additionally, these patients did not experience a relapse event.
Overall, these DOR results add to a growing body of clinical evidence and further support the development of APVO436 in combination therapy for patients with AML.
"APVO436 is a novel anti-CD3/CD123 bispecific T-cell engaging antibody that re-directs the patient’s own T cells to target and kill CD123-positive leukemic stem cells and blasts," Justin Watts, MD, associate professor of medicine, division of hematology, chief, leukemia section, at the University of Miami/Sylvester Comprehensive Cancer told Targeted OncologyTM. "The rate and duration of response to venetoclax, azacitidine, and APVO436 triplet therapy in relapsed/refractory and frontline high risk AML patients is encouraging given the historically poor treatment outcomes in these populations. Longer duration of response typically correlates with longer survival and better quality of life, and durable responses were seen in patients successfully bridged to allogeneic transplant and in those who did not go to transplant and continued on venetoclax, azacitidine, and APVO triplet therapy."
The design of this antibody-like recombinant protein therapeutic engages leukemia cells as well as T-cells of the immune system and brings them together to trigger the destruction of leukemia cells. Previously, APVO436 has received an orphan drug designation by the FDA for patients with AML.
In prior clinical trials, APVO436 led to a 91% clinical benefit when given in combination with venetoclax and azacitidine in patients with AML who are venetoclax treatment naïve. These data more than doubled the response rate in a composite benchmark across all benefit categories.
Additionally, safety data showed that APVO436 with this venetoclax and azacitidine was generally safe and well-tolerated with fewer than 1 quarter of patients within the patient population having cytokine release syndrome (CRS). In most cases, CRS was mild or moderate and was manageable in the clinic.
A phase 2 program plans to further evaluate the combination of APVO436, venetoclax, and azacitidine in the frontline and relapsed/refractory AML patient population who are venetoclax treatment naïve.
Two trials will be conducted. The first will initiate in the second half of 2023 and evaluate patients with relapsed/refractory AML, and the second will start in the first half of 2024 and look at frontline patients. The 2 trials will evaluate approximately 100 patients and interim results will be available in late 2024.
"Two phase 2 studies are currently planned, including a randomized, phase 2 study of venetoclax and azacitidine vs venetoclax, azacitidine, and APVO436 in the frontline older/unfit AML population, and a phase 2, dose-expansion study of venetoclax, azacitidine, and APVO436 in patients with relapsed/refractory AML who have failed standard induction chemotherapy," added Watts.