NCT05833763

A Phase 2 Trial of GlOfitamab anD pIrtobrutinib in Mantle Cell Lymphoma Patients With Prior BTK Inhibitor Exposure.

An Open-label, Single-arm, Phase 2 Trial of GlOfitamab anD pIrtobrutinib (LOXo-305) in Patients With Mantle Cell Lymphoma and Prior Exposure to a BTK Inhibitor

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: Australasian Leukaemia and Lymphoma Group · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to evaluate the safety and response of combining Pirtobrutinib and Glofitimab in patients with relapsed MCL. The main question it aims to answer are: * Will additive and synergistic effects be observed when using a combination of glofitamab and pirtobrutinib? * Will this combination be safe and lead to high complete- and remission rates with no residual disease? Pirtobrutinib will be given to all participants as an oral tablet for the duration of the entire study. Participants will receive other treatment in 3 phases: 1. Treatment Ramp-Up 1. Treatment with Obinutuzumab by Intravenous (IV) 2. An initial dose level of Glofitamab will evaluate step-up dosing. If excessive adverse events are observed, a lower initial dose will be used. 2. Fixed course combination phase: Treatment with Glofitamab by IV 3. Maintenance phase: Glofitamab is discontinued. 200mg oral daily

Detailed description

The goal of this clinical trial is to evaluate the safety and response of combination Pirtobrutinib and Glofitimab in patients with relapsed/refractory MCL. The main question it aims to answer are: * Will additive and synergistic effects be observed when using a combination of glofitamab and pirtobrutinib? * Will this combination be safe and lead to high complete- and MRD-negative remission rates? Participants will receive treatment based on 21 day cycles. This study design involves 3 phases: 1. Treatment Ramp-Up 1. Pre-Phase (7 days): Obinutuzumab (1000mg) will be administered intravenously (IV) on D-7 and a second dose administered between Day 6 and Day 1. 2. Cycle 1: An initial dose level of Glofitamab will evaluate step-up dosing. If excessive dose-limiting toxicity is observed, including cytokine release syndrome (CRS), a lower initial dose of 1.25mg of glofitamab will be evaluated at "dose level -1". i. Dose level 1 (14 days): * 2.5mg Glofitamab by IV on Day 1 * 10mg Glofitamab by IV on Day 8 ii. Dose level -1 (21 days): * 1.25mg Glofitamab by IV on Day 2 * 2.5mg Glofitamab by IV on Day 8 * 10mg Glofitamab by IV on Day 15 c. Cycle 2 (21 days): 30mg Glofitamab by IV on Day 1 2. Fixed course combination phase: Cycles 3-12 (21 days per cycle): 30mg of Glofitamab by IV on day 1 3. Maintenance phase: Cycles 13+ (21 days per cycle): Glofitamab discontinued. 200mg oral daily

Conditions

• Mantle Cell Lymphoma
• Mantle Cell Lymphoma Refractory

Interventions

Type	Name	Description
DRUG	Glofitamab	Glofitamab is provided as liquid concentrate for IV infusion. Each vial contains 10mg of glofitamab.
DRUG	Pirtobrutinib	Pirtobrutinib is supplied as immediate release film-coated tablets containing 50 mg, or 100 mg of active compound. Tablets are supplied in labelled, HDPE bottles and sealed with child-resistant closures.
DRUG	Obinutuzumab	Obinutuzumab is provided as a single dose 1000 mg liquid concentrate for infusion containing of 25 mg/mL obinutuzumab.
DRUG	Tocilizumab	Tocilizumab is provided as a liquid concentrate for IV infusion. Each vial contains 200mg/10mL concentrate solution

Timeline

• Start date: 2023-10-12
• Primary completion: 2032-04-01
• Completion: 2037-04-01
• First posted: 2023-04-27
• Last updated: 2024-01-08

Locations

2 sites across 1 country: Australia

Regulatory

• FDA-regulated drug study