Phase II Multicenter Study of Glofitamab Combination Therapy in Relapsed/Refractory Mantle Cell Lymphoma After CAR‑T Cell Failure

The primary objective is to assess the activity of glofitamab in patients with relapsed or refractory Mantle Cell Lymphoma who have experienced inadequate response or relapse following CAR‑T cell therapy, providing critical data on therapeutic efficacy in this high‑risk cohort. The secondary objectives are to evaluate the clinical outcome after glofitamab treatment and to characterize the safety profile of glofitamab in the same patient population, thereby addressing additional efficacy endpoints and tolerability considerations.

The trial enrolled adult individuals (age ≥ 18 years) of both sexes with histologically confirmed Mantle Cell Lymphoma who had experienced disease relapse or progression after prior CD19‑directed CAR‑T cell therapy administered at least 30 days before screening. Eligible participants were required to have an ECOG performance status of 0–2, a life expectancy greater than 12 weeks, and adequate hematologic (ANC > 1.0 × 10⁹/L, platelets ≥ 50 000/mm³, hemoglobin ≥ 8 g/dL), renal (creatinine clearance ≥ 30 mL/min), and hepatic function (AST/ALT ≤ 3 × ULN, bilirubin ≤ 1.5 × ULN). Additional criteria included resolution of prior therapy‑related adverse events to grade ≤ 1 (excluding hematologic toxicities), absence of persistent or severe neurotoxicity from CAR‑T treatment, and compliance with contraception requirements for patients of childbearing potential. The selection process focused on individuals meeting these clinical and laboratory thresholds, without specific lifestyle restrictions noted. The sponsor did not provide the total number of participants enrolled in the study.

The study is a multicenter, phase II, single‑arm, open‑label trial evaluating the activity of Mantle Cell Lymphoma patients who have relapsed or shown inadequate response after CAR‑T‑cell therapy; participants receive intravenous glofitamab (2.5 mg followed by 30 mg) in combination with obinutuzumab (2000 mg) and prophylactic tocilizumab (1600 mg) administered according to a predefined schedule, with treatment lasting up to 12 months and follow‑up extending to the end‑of‑study visit. After written informed consent, a screening visit confirms eligibility criteria, including age ≥ 18 years, adequate organ function, ECOG 0–2, and documented disease status per central pathology review. Eligible subjects then commence the baseline visit (day 0) for drug administration, followed by regular study visits at predefined intervals (e.g., every 4 weeks) to monitor efficacy (complete and overall response rates per Lugano 2014 criteria), safety (CTCAE‑graded adverse events), and pharmacologic parameters; response assessments are performed at month 6 (C6) and month 12 (C12). The end‑of‑study visit occurs after the final treatment cycle or upon early discontinuation, at which point final efficacy and safety evaluations are completed. Expected participant involvement ranges from screening through the 12‑month treatment period and subsequent follow‑up, but may be terminated earlier for disease progression, unacceptable toxicity, withdrawal of consent, or death.

The experimental agent glofitamab is supplied as an intravenous solution without a defined pharmaceutical form. Two dose levels are employed: an initial lead‑in dose of 2.5 mg administered intravenously, followed by subsequent doses of 30 mg given intravenously according to the study’s dosing schedule. Each administration is performed as an infusion, and the timing of repeat dosing is dictated by the protocol. Compliance with the dosing schedule is monitored through infusion logs and pharmacovigilance assessments.

The trial includes the investigational monoclonal antibody obinutuzumab, administered intravenously at a fixed dose of 2000 mg per infusion. Doses are delivered in accordance with the protocol‑specified schedule, and infusion records are used to verify adherence.

The background therapy tocilizumab is provided as an intravenous preparation, dosed at 1600 mg per infusion. It is administered as outlined in the study protocol, with administration timing recorded to ensure protocol compliance.

All intravenous products are prepared and administered by qualified personnel. Participant compliance is assessed by reviewing infusion documentation, drug accountability logs, and scheduled laboratory evaluations throughout the study period.

Efficacy will be evaluated using radiologic and clinical response criteria assessed by an independent review committee according to the Lugano 2014 classification. The primary efficacy parameter is the Complete Response Rate (CRR) observed at any time during study treatment. Secondary efficacy parameters include the Overall Response Rate (ORR), defined as the proportion of patients achieving a complete or partial response, measured at cycle 6 (C6) and cycle 12 (C12); the Complete Response Rate at the end of treatment (C12); Progression Free Survival (PFS) from study inclusion to disease progression or death; Overall Survival (OS) from study inclusion to death; Duration of Response (DOR) from first documented response to progression or death; Time to Next Treatment (TTNT) from study inclusion to initiation of subsequent therapy; and Event Free Survival (EFS) from study inclusion to disease progression, death, or start of next anti‑lymphoma treatment. Adverse events will be recorded and graded per the latest CTCAE version.