NCT06746519

BN104 in Combination With Chemotherapy or Targeted Agents for Acute Myeloid Leukemia

A Phase I/II , Multicenter, Open Label Clinical Study Evaluating the Safety, Pharmacokinetics, and Efficacy of the Combination of the Menin Inhibitor BN104 for the Treatment of Patients With Acute Myeloid Leukemia

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 135 (estimated)
• Sponsor: Chen Suning · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The Phase I/II trial is to learn the safety, pharmacokinetics, and preliminary efficacy of BN104 taken twice daily combined with Intensive Chemotherapy or Venetoclax/Azacitidine in patients with acute myeloblastic leukemia.

Detailed description

The study is divided into 2 phases. Phase1 dose escalation part will enroll 90 patients to evaluate safety and tolerance of BN104 taken twice daily combined with Intensive Chemotherapy or Venetoclax/Azacitidine in patients with newly diagnosed or relapsed/refractory (R/R) acute myeloblastic leukemia with specific mutations (KMT2A gene rearrangement ,NPM1 gene mutation and NUP98 rearrangement). Patients will be allocated into 3 cohorts based on their disease status quo. Each cohort will use 3+3 dose escalation model, the starting dose level is 200mg of BN104 taken twice daily combined with Intensive Chemotherapy or Venetoclax/Azacitidine. \- Cohort A: Newly diagnosed AML patients with specific mutations who are suitable to receive BN104 combined with intensive chemotherapy(cytarabine with idarubicin or daunorubicin), which short as"7+3 induction regimen", consisting of remisson introdcution,consolidation and BN104 maintenance phase. Patients who achieve a complete remission (CR), complete remission with partial hematologic recovery (CRh), or complete remission with incomplete hematologic recovery (CRi) after 1 or 2 induction cycles may proceed on to consolidation therapy. Patients who do not achieve CR,CRh or CRi after 1 or 2 induction regimens will be considered a treatment failure and thus will be terminated from study treatment. Patients entering the consolidation phase then received an intravenous infusion of cytarabine 1-2 g/m2 every 12 hours (Q12H), using a total of 6 doses, which could be administered either consecutively at D1-3 or separately at D1, D3, and D5, depending on the study center's treatment routine. In each treatment cycle, the indicated dose of BN104 was given orally twice daily until the next cycle of consolidation treatment. Patients entering the consolidation phase receive at least 1 cycle of consolidation therapy and a maximum of 4 cycles. After completion of consolidation therapy, patients who remain in CR, CRh, or CRi may continue to receive BN104 monotherapy maintenance therapy at the indicated dose administered twice daily for 1 cycle every 28 days until completion of 26 cycles of maintenance therapy, disease relapse/progression, receipt of hematopoietic stem cell transplantation, intolerable toxicity, loss to visit, withdrawal of informed consent, death, or other circumstances that, in the judgment of the investigator, require the termination of study drug, whichever occurs first. * Cohort B: Newly diagnosed AML patients with specific mutations who are ≥75 years of age or \<75 years of age but are not suitable for intensive chemotherapy due to co-morbidities. The regimen is BN104 taken twice daily combined with azacitidine and venetolax. Venetolax (100 mg, day 1; 200 mg, day 2; 400 mg, days 3-28) orally in combination with azacitidine 75 mg/(m2-d) subcutaneously x 7 days (D1-7), and after the target administered dose of Venegra was reached, BN104 was administered orally at the indicated dose twice daily in a continuous manner (D1-28, cycle 1 as D4-28) in 28-day treatment cycles. * Cohort C: relapsed/refractory AML patients with specific mutations, prior treatment failure with menin inhibitors is required. The regimen is BN104 taken twice daily combined with azacitidine and venetolax. Any patient may receive HSCT after termination of study treatment at any stage if assessed by the investigator to be amenable to hematopoietic stem cell transplantation (HSCT.) Patients whose patients are still in CR, CRh, or CRi after receiving HSCT may still continue to initiate BN104 monotherapy if they meet the appropriate criteria. Phase II expansion part will enroll 30-45 patients and be conducted at the selected dose level to further evaluate the safety and tolerability of BN104 combined with Intensive Chemotherapy or Venetoclax/Azacitidine, as well as preliminary efficacy in Acute leukemia subjects with specific mutations (KMT2A gene rearrangement, NPM1 gene mutation and NUP98 mutation). * Cohort D: Newly diagnosed AML patients with KMT2A rearrangements, NPM1 mutations, or NUP98 rearrangements who are fit for intensive chemotherapy. * Cohort E: Newly diagnosed AML patients with KMT2A rearrangements, NPM1 mutations or NUP98 rearrangements who are unfit for intensive chemotherapy. * Cohort F: relapsed/refractory AML patients with KMT2A rearrangement, NPM1 mutation or NUP98 rearrangement. It is planned to enroll 10-15 patients in each cohort accordingly

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	BN104 combined Intensive Chemotherapy or Venetoclax/Azacitidine	The starting dose cohort(200mg BID N104) combined Intensive Chemotherapyor Venetoclax/Azacitidine. Each treatment cycle is anticipated to be 28 days in length, although cycle delays may be made due to delayed count recovery.

Timeline

• Start date: 2024-12-25
• Primary completion: 2025-12-30
• Completion: 2027-06-30
• First posted: 2024-12-24
• Last updated: 2024-12-24

Locations

1 site across 1 country: China