GLOFITAMAB for Mantle cell lymphoma

Stratification factors

• Biological risk (high-risk vs standard-risk defined by MIPI-c and Ki67)
• TP53 mutation status
• TP53 overexpression (> 50%)

Inclusion criteria

• {"criterion_text":"- Cohort A (R/R MCL): Relapse or progression following at least one prior line of anti-neoplastic standard therapy, which included at least an anti CD20 antibody plus an anthracycline and/or bendamustine and/or fludarabine."}
• {"criterion_text":"- The following laboratory values at screening (unless related to MCL) : Platelets ≥75,000 cells/μL (≥50,000 cells/μL required if caused by bone marrow involvement or splenomegaly due to MCL), independent of transfusions within 7 days of Screening assessment.Hemoglobin ≥ 8 g/dL or ≥ 6 g/dL in patients with documented bone marrow involvement considered to impair hematopoiesis. Calculated creatinine clearance ≥30 mL/min. Transaminases (AST and ALT) ≤ 3 x ULN. Total Bilirubin ≤ 1.5 x ULN or ≤ 3 x ULN with documented Gilbert-MeulengrachtSyndrome or liver involvement by MCL. aPTT and PT ≤1.5 x ULN, unless explained by concomitant anticoagulant medication, and in the opinion of the investigator not associated with an increased bleeding risk."}
• {"criterion_text":"- Adequate cardiopulmonary function defined as: cardiac ejection fraction ≥ 45% at all assessments within the last 12 months from screening, no evidence of pericardial effusion as determined by echocardiography; no clinically significant pleural effusion; baseline oxygen saturation > 92% on room air"}
• {"criterion_text":"- No evidence of CNS-disease"}
• {"criterion_text":"- Written informed consent form according to ICH/ E6 (R2) CTR and national regulations, ability to follow study instructions and likely to attend and complete all required visits."}
• {"criterion_text":"- Sexually active men and women of child-bearing potential must agree to use one of the highly effective contraceptive methods (combined oral contraceptives using two hormones, progestogen-only hormonal contraception associated with inhibition of ovulation, contraceptive implants, injectables, intrauterine devices, sterilized partner) together with one of the barrier methods (latex condoms, diaphragms, contraceptive caps) while on study; this should be maintained for 6 months after the last dose of study drug"}
• {"criterion_text":"- Negative serum or urine pregnancy test (Females of childbearing potential only, females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient)."}
• {"criterion_text":"- Availability of tissue samples for central pathology review"}
• {"criterion_text":"- Cohort A (R/R MCL): Aged 18 years or older."}
• {"criterion_text":"- Cohort B (elderly TN MCL): Previously untreated."}
• {"criterion_text":"- Cohort B (elderly TN MCL): Age ≥ 65 years or ≥ 60 years who are in the opinion of the investigator not suited for intensive, cytarabine and platinum-based induction treatment regimens"}
• {"criterion_text":"- Histologically confirmed diagnosis of MCL according to WHO classification, with documentation of either overexpression of cyclin D1 or presence of t(11;14)."}
• {"criterion_text":"- Stage II-IV (Ann Arbor)"}
• {"criterion_text":"- At least 1 measurable lesion according to the Lugano Response Criteria (>1.5 cm nodal lesion or > 1 cm extranodal lesion)"}
• {"criterion_text":"- ECOG performance status ≤ 2"}
• {"criterion_text":"- The patient is able to take oral medications"}

Exclusion criteria

• {"criterion_text":"- Known history of hypersensitivity to the investigational drug or to drugs with a similar chemical structure"}
• {"criterion_text":"- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Known active CMV infection."}
• {"criterion_text":"- Positive test results for chronic HBV/HCV infection (defined as positive HBsAg serology) or HIV (mandatory testing). Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA is undetectable. Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA."}
• {"criterion_text":"- History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement."}
• {"criterion_text":"- History of or active autoimmune disease (e.g. Crohn’s disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic medication within the last 2 years."}
• {"criterion_text":"- Known severe primary immunodeficiency."}
• {"criterion_text":"- Any medical condition likely to interfere with assessment of safety or efficacy of study treatment."}
• {"criterion_text":"- Live vaccine ≤ 6 weeks prior to planned start of study treatment."}
• {"criterion_text":"- Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow up schedule"}
• {"criterion_text":"- Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of pirtobrutinib."}
• {"criterion_text":"- History of bleeding diathesis"}
• {"criterion_text":"- Simultaneously active participation in another clinical study involving an investigational medicinal product within 30 days prior to enrolment"}
• {"criterion_text":"- Previous treatment with an anti-CD20 directed bispecific antibody"}
• {"criterion_text":"- Previous treatment with a BTKi"}
• {"criterion_text":"- Previous CART treatment"}
• {"criterion_text":"- Steroid therapy (prednisolone ≤100mg daily or equivalent for up to 14 days are permitted during screening for control of lymphoma related symptoms)"}
• {"criterion_text":"- Targeted agents, investigational agents, therapeutic monoclonal antibodies/antibody drug conjugates or cytotoxic chemotherapy must be completed 5 half-lives or 2 weeks (whichever is longer) prior to study treatment"}
• {"criterion_text":"- History of allogeneic transplantation"}
• {"criterion_text":"- Major surgery or significant traumatic injury within 28 days of screening, major surgery does not include uncomplicated lymph node resection/ laparoscopy for the diagnosis of MCL"}
• {"criterion_text":"- Requirement of therapeutic anticoagulation with a vitamin K antagonist (warfarin, phenprocoumon) or of treatment with strong CYP3A4 inhibitors or inducers"}
• {"criterion_text":"- Immunoconjugated antibody treatment within 10 weeks prior to enrolment"}
• {"criterion_text":"- Broad field radiation (≥ 30% of the bone marrow or whole brain radiotherapy) must be completed 14 days prior to treatment start. Palliative limited field radiation must be completed 7 days prior to treatment start."}
• {"criterion_text":"- Subjects with a physical or psychiatric condition which at the investigator’s discretion may put the subject at risk, may confound the study results, or may interfere with the subject’s participation in this clinical study"}
• {"criterion_text":"- Prior treatment-related AEs must have recovered to Grade ≤ 1 with the exception of alopecia and Grade 2 peripheral neuropathy."}
• {"criterion_text":"- Known or persistent abuse of medication, drugs, or alcohol."}
• {"criterion_text":"- Serious concomitant disease interfering with a regular therapy according to the study protocol: Clinically significant cardiovascular disease such as symptomatic arrhythmias, congestive heart failure, unstable angina, myocardial infarction, cardiac angioplasty or stenting within 12 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification"}
• {"criterion_text":"- Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec on at least 2/3 consecutive electrocardiograms (ECGs), and mean QTcF > > 470 msec on all 3 ECGs, during screening. QTcF is calculated using Fridericia’s formula (QTcF): QTcF = QT/(RR*0.33)"}
• {"criterion_text":"- Severe endocrinological conditions (e.g. severe, not sufficiently controlled diabetes mellitus)."}
• {"criterion_text":"- Current or planned pregnancy (during the study or within 1 month of the last study treatment) or nursing women (within 1 week from the last study treatment)"}
• {"criterion_text":"- History of or active malignancy other than MCL, non-melanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast). History of localized prostate cancer acceptable only if diseasefree and PSA within normal range for at least 3 years"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is progression-free survival status 24 months from treatment start and will be analyzed by cohort and stratum (cohort A, cohort B high-risk, and cohort B standard-risk). Analysis will be performed on a modified ITT population: eligible patients who received at least one dose of any IMP.","definition_or_measurement_approach":"Progression-free survival status at 24 months from treatment start; analysis by cohort and stratum (cohort A; cohort B high-risk; cohort B standard-risk). Population: modified ITT (eligible patients who received ≥1 dose of any IMP)."}

Secondary endpoints

• {"endpoint_text":"- Progression free survival time from treatment start","definition_or_measurement_approach":"Time-to-event measure: time from treatment start to progression or death."}
• {"endpoint_text":"- Complete remission rate (CR) and overall response rate (ORR: CR, PR) 8 months from treatment start (after completion of glofitamab-treatment, prior to cycle 13) and approximately 24 months (prior to cycle 30) from treatment start.","definition_or_measurement_approach":"Response rates (CR, ORR) assessed at ~8 months (after glofitamab completion, prior to cycle 13) and ~24 months (prior to cycle 30)."}
• {"endpoint_text":"- Rate of PET negative CR (complete metabolic response rate, Lugano criteria) 8 months from treatment start (after completion of glofitamab-treatment prior to cycle 13) and 24 months (prior to cycle 30) from treatment start","definition_or_measurement_approach":"PET-based complete metabolic response rate assessed using Lugano criteria at ~8 and ~24 months."}
• {"endpoint_text":"- Best response, time to best response, time to first response from treatment start","definition_or_measurement_approach":"Standard response assessments over time: best overall response, time to best response, time to first response measured from treatment start."}
• {"endpoint_text":"- Duration of response.","definition_or_measurement_approach":"Time from first documented response to progression or death."}
• {"endpoint_text":"- Duration of CR","definition_or_measurement_approach":"Time from documentation of complete remission to relapse/progression or death."}
• {"endpoint_text":"- Overall survival (OS) time from treatment start","definition_or_measurement_approach":"Time from treatment start to death from any cause."}
• {"endpoint_text":"- Safety: adverse events, serious adverse events, toxicities (CTCAE v5.0 and ASTCT 2019 for CRS/ICANS)","definition_or_measurement_approach":"Safety assessed by recording AEs, SAEs and toxicities graded per CTCAE v5.0; CRS/ICANS graded per ASTCT 2019 criteria."}

Denmark

Earliest CTIS Part Ii Submission Date

06-08-2025

Latest Decision Or Authorization Date

12-08-2025

Processing Time Days

6

Number Of Sites

4

Number Of Participants

13

Germany

Earliest CTIS Part Ii Submission Date

21-07-2025

Latest Decision Or Authorization Date

15-08-2025

Processing Time Days

25

Number Of Sites

12

Number Of Participants

42

Sweden

Earliest CTIS Part Ii Submission Date

22-07-2025

Latest Decision Or Authorization Date

12-08-2025

Processing Time Days

21

Number Of Sites

5

Number Of Participants

16

Norway

Earliest CTIS Part Ii Submission Date

08-08-2025

Latest Decision Or Authorization Date

13-08-2025

Processing Time Days

5

Number Of Sites

2

Number Of Participants

6

Spain

Earliest CTIS Part Ii Submission Date

05-08-2025

Latest Decision Or Authorization Date

18-11-2025

Processing Time Days

105

Number Of Sites

6

Number Of Participants

19

Primary sponsor

Full Name

Klinikum der Universitaet Muenchen AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Third parties

• {"country":"Germany","full_name":"Universitaetsklinikum Schleswig-Holstein AöR","duties_or_roles":"code 15: Pathological analysis of body material","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Proinnovera GmbH","duties_or_roles":"codes: 1, 12, 5","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Odense University Hospital","duties_or_roles":"code 1","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Universitaetsklinikum Schleswig-Holstein AöR","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Klinikum der Universitaet Muenchen AöR","duties_or_roles":"codes: 10, 15 (Safety), 6","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Rostock University Medical Center","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}