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

NCT05833763 | Recruiting Phase 2 FDA Drug

• 1 other identifier: NHL37
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief 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:
• Treatment Ramp-Up
• Treatment with Obinutuzumab by Intravenous (IV)
• An initial dose level of Glofitamab will evaluate step-up dosing. If excessive adverse events are observed, a lower initial dose will be used.
• Fixed course combination phase: Treatment with Glofitamab by IV
• Maintenance phase: Glofitamab is discontinued. 200mg oral daily

Conditions

Mantle Cell Lymphoma; Mantle Cell Lymphoma Refractory

Outcome Measures

Primary Outcomes (1)

• To 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

  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.

Secondary Outcomes (7)

• Complete response rate using the Lugano Criteria for response assessment at end of 12 cycles of Glofitamab

  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)

  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.

  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

  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)

  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.

Study Arms (1)

Study Treatment

EXPERIMENTAL

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

Drug: Glofitamab; Drug: Pirtobrutinib; Drug: Obinutuzumab; Drug: Tocilizumab

Interventions

Glofitamab DRUG

Glofitamab is provided as liquid concentrate for IV infusion. Each vial contains 10mg of glofitamab.

Study Treatment

Pirtobrutinib DRUG

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.

Study Treatment

Obinutuzumab DRUG

Obinutuzumab is provided as a single dose 1000 mg liquid concentrate for infusion containing of 25 mg/mL obinutuzumab.

Study Treatment

Tocilizumab DRUG

Tocilizumab is provided as a liquid concentrate for IV infusion. Each vial contains 200mg/10mL concentrate solution

Study Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 18 years old or above
• A confirmed diagnosis of MCL according to World Health Organization (2016) criteria
• At least one site of measurable disease not previously irradiated (defined as at least one bi-dimensionally measurable nodal lesion of greater than or equal to 1.5cm in longest dimension)
• Life expectancy (in the opinion of the investigator) of greater than or equal to 18 weeks
• Prior therapy with a BTK inhibitor alone or in combination and:
• Progression or relapse post BTK inhibitor or
• Failed to achieve PR following 12 weeks of BTK inhibitor therapy
• Prior TRAEs must have recovered to Grade 1 or less with the exception of alopecia, peripheral neuropathy and lymphopenia.
• ECOG 0-2
• Adequate washout of prior therapies:
• Broad field radiation (greater than or equal to 30% of the bone marrow or whole brain radiotherapy) must be completed 14 days prior to study treatment
• Palliative limited field radiation must be completed 7 days prior to study treatment.
• Targeted agents, investigational agents, therapeutic monoclonal antibodies/antibody drug conjugates or cytotoxic chemotherapy must be completed 5 half-lives or 2 weeks (whichever is shorter) prior to study treatment (except for BTK inhibitors which may be continued until 1 day prior to planned first therapy with pirtobrutinib)
• Steroids (prednisolone less than or equal to 100mg daily or equivalent for up to 14 days are permitted during screening for control of lymphoma related symptoms
• Ability to take oral medications

You may not qualify if:

• Inability to comply with protocol mandated hospitalisations
• For patients enrolling on the safety cohort, a history of allogeneic transplantation within 12 months of enrolment or ongoing chronic GVHD or immunosuppressive therapy.
• Autologous SCT or CAR-T therapy within 6 weeks of enrolment
• Active central nervous system involvement with MCL
• Prior treatment with pirtobrutinib or demonstrated refractoriness to a CD20xCD3 bispecific antibody.
• Have a known severe hypersensitivity to any of the excipients of pirtobrutinib, glofitamab, tocilizumab or obinutuzumab.
• History of stroke or intracranial haemorrhage within six months of enrolment.
• Live vaccination within 28 days of enrolment.
• Major surgery or significant traumatic injury within 28 days of study treatment or the anticipation of major surgery during study treatment (surgical procedures for the diagnosis of lymphoma such as lymph node resection/ laparoscopy are allowed provided patient is considered fit for treatment as judged by investigator)
• Significant cardiovascular disease defined as:
• Unstable angina or acute coronary syndrome within 2 months of registration
• History of myocardial infarction within 3 months prior to registration
• Documented LVEF by any method of = 40% during screening
• Grade 3 or higher NYHA functional classification system of heart failure
• Uncontrolled or symptomatic arrhythmias

Sponsors & Collaborators

• Australasian Leukaemia and Lymphoma Group: lead

Study Sites (2)

Peter MacCallum Cancer Centre

Parkville, Victoria, 3050, Australia

RECRUITING

Sir Charles Gairdener

Nedlands, Western Australia, 6009, Australia

RECRUITING

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

glofitamab; pirtobrutinib; obinutuzumab; tocilizumab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2023
• First Posted: April 27, 2023
• Study Start: October 12, 2023
• Primary Completion (Estimated): April 1, 2032
• Study Completion (Estimated): April 1, 2037
• Last Updated: January 8, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2)