NCT04851834

NTX-301 Monotherapy in Advanced Solid Tumours and in Combination With Platinum-based Chemotherapy in Advanced Ovarian & Bladder Cancer and in Combination With Temozolomide in High-grade Glioma

A Phase 1/2, Open-label, Dose-exploration and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NTX-301 Monotherapy in Advanced Solid Tumours, and in Combination With Platinum-based Chemotherapy in Advanced Ovarian & Bladder Cancer, and in Combination With Temozolomide as Adjuvant (Maintenance) Therapy in High-grade Glioma (Optional Arm)

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Xennials Therapeutics Australia Pty Ltd · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1/2, open-label, dose-exploration, combination/expansion study, which will start by evaluating the safety and tolerability of NTX-301, an oral DNMT1 inhibitor, as a monotherapy in patients with advanced solid tumours, who have failed treatment with available therapies known to be active for treatment of their corresponding disease. It will then explore the safety and tolerability of NTX-301 in combination with platinum-based therapy in patients with ovarian and bladder cancer. Optionally, the safety and tolerability of NTX-301 in combination with Temozolomide (TMZ) in patients with Isocitrate Dehydrogenase 1 (IDH1) mutated high-grade glioma will also be assessed.

Detailed description

Dose Exploration (Phase 1a, n\~25): This part of the study will assess the safety and tolerability of NTX-301 and to identify the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D). It will initiate with a dose escalation using a 3+3 design. Combination Dose and Disease Expansion (Phase 1b-2a, n\~60): The study will be expanded in specific subsets of patients with solid tumours and with combination therapy as follows: * Arm 1 (Phase 1b, n\~20): Dose Escalation, NTX-301 platinum-based doublet therapy * Arm 2 (Phase 2a, n\~40): Dose Expansion, NTX-301 platinum-based doublet therapy Patients with advanced ovarian \& bladder cancer considered to be incurable by the investigator and for which available anti-cancer therapy has been exhausted will be enrolled for this component. Patients will be given NTX-301 at the MTD determined in Phase 1a. This will be combined with a platinum-based agent that will be administered by IV infusion. Optional Cohort -High-Grade Glioma Combination Dose \& Disease Expansion (Phase 1b-2a, n\~40) * Arm 3 (Phase 1b, n\~20): Dose Escalation, NTX-301 combination therapy with TMZ * Arm 4 (Phase 2a, n\~20): Dose Expansion, NTX-301 combination therapy with TMZ Patients with IDH1 mutated high-grade glioma that have commenced initial chemoradiotherapy with temozolomide and are yet to commence Temozolomide maintenance therapy will be enrolled for this component. Patients will be given NTX-301 at the MTD determined in Phase 1a. This will be combined with TMZ that will be administered orally.

Conditions

• Advanced Solid Tumor
• Platinum-Resistant Ovarian Cancer
• Platinum-Resistant Urothelial Carcinoma
• High-grade Glioma

Interventions

Type	Name	Description
DRUG	NTX-301	Oral hypomethylating agent
DRUG	Platinum-based Chemotherapy	Standard of care for ovarian and bladder cancer
DRUG	Temozolomide	Standard of care for high-grade glioma

Timeline

• Start date: 2021-08-25
• Primary completion: 2022-11-08
• Completion: 2022-11-08
• First posted: 2021-04-20
• Last updated: 2022-12-20

Locations

2 sites across 1 country: Australia

Regulatory

• FDA-regulated drug study