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
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
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Glofitamab is provided as liquid concentrate for IV infusion. Each vial contains 10mg of glofitamab.
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.
Obinutuzumab is provided as a single dose 1000 mg liquid concentrate for infusion containing of 25 mg/mL obinutuzumab.
Tocilizumab is provided as a liquid concentrate for IV infusion. Each vial contains 200mg/10mL concentrate solution
Peter MacCallum Cancer Centre
Parkville, Victoria, Australia
RECRUITINGSir Charles Gairdener
Nedlands, Western Australia, Australia
RECRUITINGTo evaluate the efficacy of combination Pirtobrutinib and Glofitmab in patients with relapsed/refractory MCL and prior BTK inhibitor exposure.
Determined by the complete response (CR) rate according to Lugano criteria
Time frame: Following six cycles (or approximately 18 weeks following first treatment). Cycle 1 is 14 days in duration and cycles 2 to 6 are 21 days in duration.
Complete response rate using the Lugano Criteria for response assessment at end of 12 cycles of Glofitamab
Using the Lugano Criteria for response assessment
Time frame: When all patients have completed 12 cycles of Glofitamab. Cycle 1 is 14 days in duration and cycles 2 to 12 are 21 days in duration.
Assessment of adverse events (eg. fatigue, diarrhoea, confusion, nausea, constipation, anaemia, dyspnoea)
Incidence, nature and severity of adverse events are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
Time frame: Analysis of the adverse events will be completed in line with the primary and secondary endpoints; When all patients have completed 6 cycles of protocol treatment, when all patients have completed 12 cycles of treatment.
Overall response rates (complete or partial response) to combination therapy.
Using the Lugano criteria
Time frame: At the end of combination therapy (cycle 12).Cycle 1 is 14 days in duration and cycles 2 to 12 are 21 days in duration.
Overall response rates
Using the Lugano criteria
Time frame: At the end of combination therapy (cycle 12). Cycle 1 is 14 days in duration and cycles 2 to 12 are 21 days in duration.
Absence of minimal residual disease (MRD)
Measured by aggregate measure of peripheral blood and/or bone marrow flow cytometry, PCR and ctDNA
Time frame: Following six cycles and 12 cycles of combination treatment. Cycle 1 is 14 days in duration and cycles 2 to 12 are 21 days in duration.
Progression-free survival (PFS)
Determined based on the modified Lugano criteria.
Time frame: Progression is measured from the date of registration to the date of first progression at any site or date of death due to any cause. Patients will be followed assessed until the last patient registered completes 5 years of follow up.
Duration of response
Defined as the time from registration to date of death from any cause. Patients who have not died by the study close-out date will be censored at their last visit. Patients who are lost to follow-up before the close-out date and who are not known to have died will be censored at the date they were last known to be alive
Time frame: Patient's will be followed assessed until the last patient registered completes 5 years of follow up.
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