Phase 2/3 Randomized Study of Pivekimab Sunirine Plus Venetoclax and Azacitidine in Adults with Newly Diagnosed AML Ineligible for Intensive Chemotherapy

The primary objective is to determine whether the addition of pivekimab sunirine to venetoclax and azacitidine improves complete remission rates in adult patients with newly diagnosed Acute Myeloid Leukemia who are ineligible for intensive chemotherapy, and, in the phase 3 portion, to assess superiority of this regimen for both complete remission and overall survival compared with venetoclax plus azacitidine alone. The secondary objective evaluates whether the combination therapy enhances the composite CR+CRi and CR+CRh response rates relative to the standard venetoclax‑azacitidine regimen.

The trial enrolled 65 adult participants of both sexes with newly diagnosed acute myeloid leukemia who were deemed ineligible for intensive chemotherapy; the age range corresponded to adult categories as defined by the protocol. All subjects were required to have a confirmed AML diagnosis according to WHO criteria, a white‑blood‑cell count below 25 × 10⁹/L (hydroxyurea could be used to achieve this threshold), and adequate renal function with a creatinine clearance of ≥30 mL/min. General health status allowed enrollment of patients who could tolerate the study regimen but did not meet criteria for more aggressive treatment. No specific dietary, physical‑activity, or habit restrictions were stipulated as part of eligibility.

The study is a randomized, double‑blind, controlled Phase 2/3 trial evaluating the safety and efficacy of intravenous Pivekimab Sunirine combined with oral Venetoclax and azacitidine in adult participants with newly diagnosed Acute Myeloid Leukemia who are ineligible for intensive chemotherapy. After an initial screening visit to confirm diagnosis, assess eligibility criteria (including WHO classification, white‑blood‑cell count < 25 × 10⁹/L, and renal function), participants are randomized 1:1 to receive either the investigational combination or standard therapy (Venetoclax + azacitidine). Study treatment is administered in 28‑day cycles with scheduled clinic visits at baseline (Day 1 of Cycle 1), weekly safety assessments during the first two cycles, and thereafter every four weeks until disease progression, withdrawal, or completion of the planned 24‑month follow‑up period. An end‑of‑study visit occurs 30 days after the last dose to collect final efficacy and safety data. Total participant involvement is expected to be up to 30 months, including screening, treatment, and follow‑up. Early termination may occur if a participant experiences a treatment‑related serious adverse event, fails to meet predefined laboratory safety thresholds, withdraws consent, or if disease progression is documented according to protocol criteria.

The study evaluates a combination therapy in adult participants with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy.

Venetoclax is supplied as a film‑coated tablet for oral administration. The tablet contains a dose of 00 mg per unit, as defined in the protocol.

Azacitidine is provided as an injectable solution for intravenous injection. The formulation is supplied at a concentration of 00 mg/ml.

Pivekimab Sunirine is presented as a powder for infusion for intravenous administration. The powder is reconstituted to deliver a dose of 00 mg per infusion.

In the experimental arm, participants receive the combination of Pivekimab Sunirine, Venetoclax, and Azacitidine according to the dosing schedule defined in the study protocol. The comparator arm consists of the standard‑of‑care regimen of Venetoclax plus Azacitidine administered using the same routes and dosing parameters.

Efficacy will be evaluated primarily by the proportion of participants achieving Complete remission (CR) and by Overall Survival (OS) in the Phase 3 portion of the study. In Phase 2, the primary efficacy endpoint is the CR rate. Secondary efficacy assessments include the composite response rate, the Duration of CR (DoCR), and several patient‑reported outcome measures. Quality‑of‑life instruments employed are the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ‑C30) covering multiple domains, the European Quality of Life 5 Dimensions (EQ‑5D‑5L) utility index and visual analog scale, and the Functional Assessment of Cancer Therapy – General Population 5 (FACT GP5). Additional secondary endpoints are the percentage of participants attaining transfusion independence, conversion from transfusion dependence to independence, and changes from baseline in the physical functioning and other domains of the EORTC QLQ‑C30.