Phase II Open‑Label Study of Cevostamab Combined with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma Post‑BCMA CAR‑T Therapy

Multiple myeloma patients previously treated with BCMA‑targeted CAR‑T therapy are evaluated for the efficacy of cevostamab combined with pomalidomide and dexamethasone. The primary objective is to determine the overall response rate of the regimen, providing a direct assessment of antitumor activity in this heavily pre‑treated population. Secondary objectives include:

• Evaluation of deeper efficacy endpoints: very good partial response or better, complete response or better, duration of response, progression‑free survival, overall survival, MRD‑negative complete response at 9 months, overall MRD‑negative complete response, time to response, time to best response, and progression‑free survival after initiation of subsequent therapy (PFS2).
• Assessment of health‑related quality of life using time to confirmed deterioration in the Disease Symptoms Scale (EORTC QLQ‑MY20) and Global Health Status/Quality of Life (EORTC QLQ‑C30).
• Safety monitoring of the combination therapy.
• Evaluation of immunogenicity of cevostamab.

The trial enrolled adult patients diagnosed with Multiple Myeloma who were eligible for treatment with cevostamab in combination with pomalidomide and dexamethasone. Both male and female participants were included, and the population encompassed individuals considered vulnerable under regulatory definitions. The age range covered the standard adult categories, corresponding to the study’s age‑range codes for middle‑aged and older adults. Sponsor data did not provide the total number of participants. Selection required a confirmed diagnosis according to International Myeloma Working Group criteria, prior exposure to anti‑CD38 therapy, a proteasome inhibitor, and lenalidomide, and receipt of a single line of BCMA‑targeted CAR T‑cell therapy. Key eligibility criteria included an ECOG Performance Status of 0 or 1 (or 2 if limited to myeloma‑related symptoms), a life expectancy of at least 12 weeks, and resolution of prior treatment‑related adverse events to ≤ Grade 1 (excluding alopecia). No specific dietary, physical activity, or habit requirements were detailed in the available information.

The study is a Phase II, single‑arm, open‑label, multicenter investigation evaluating the efficacy and safety of intravenous cevostamab in combination with oral pomalidomide and intravenous dexamethasone in patients with previously treated Multiple Myeloma who have received one prior BCMA‑targeted CAR‑T cell therapy; the overall trial period spans from October 2026 to January 2031. Eligible participants undergo an initial screening visit to confirm eligibility criteria, including ECOG performance status 0–1, life expectancy ≥12 weeks, and documented prior BCMA‑CAR‑T therapy, after which baseline assessments are performed and study treatment is initiated. Subsequent study visits are scheduled at regular intervals (e.g., every 3 weeks during the first two cycles and thereafter per protocol) to administer the CevosPd regimen, monitor disease response per IMWG criteria, assess adverse events using NCI CTCAE v5.0 and ASTCT grading, and collect laboratory, vital sign, and patient‑reported outcome data; an end‑of‑study visit occurs after the final follow‑up period, which may extend up to approximately 12 months or until disease progression, withdrawal, or protocol‑defined discontinuation. Participant involvement therefore encompasses the screening period, continuous treatment and monitoring visits, and the concluding assessment, with early termination permitted according to protocol‑specified criteria such as unacceptable toxicity, disease progression, or participant withdrawal.

The experimental agent Cevostamab is supplied as a concentrate for solution for infusion and is administered by intravenous infusion. The infusion is prepared according to the study‑specified dilution instructions and delivered over the prescribed infusion time. Dosing and frequency are defined in the protocol and are recorded for each administration; the agent is designated as an orphan drug.

Pomalidomide is provided as hard capsules in two strengths (1 mg and 2 mg). The capsules are taken orally according to the dosing schedule outlined in the protocol, typically once daily on designated treatment days. Capsule strength selection follows the individual patient’s dosing plan, and compliance is monitored through pill counts and patient diaries.

Dexamethasone is administered intravenously. The preparation is given as an IV dose on the days specified by the treatment schedule, often concomitantly with the investigational infusion. Dose amounts and timing are captured in the infusion record, and adherence to the dosing schedule is verified by review of medication administration records.

Efficacy will be evaluated using a set of predefined endpoints. The primary efficacy parameter is the overall response rate (ORR), defined as the proportion of participants achieving a best overall response of partial response (PR) or better according to the International Myeloma Working Group (IMWG criteria). Secondary efficacy parameters include the rates of very good partial response (VGPR) or better, complete response (CR) or stringent CR, depth of response (duration of response, DOR), progression‑free survival (PFS), overall survival (OS), and time‑to‑event measures such as time to response (TTR), time to best response (TTBR), and second progression‑free survival (PFS2). Additional secondary endpoints comprise MRD‑negative CR rates assessed at 9 months (±90 days) post‑enrollment and at any time point before disease progression, with MRD evaluated by next‑generation sequencing (NGS) at a sensitivity threshold of 10⁻⁵, as well as patient‑reported outcomes related to disease symptoms, global health status/quality of life (GHS/QoL), and fatigue using the European Organisation for Research and Treatment of Cancer questionnaires (EORTC QLQ‑MY20 and EORTC QLQ‑C30).

Response assessments will be performed by applying the IMWG criteria to clinical and laboratory data collected at baseline and at scheduled study visits. MRD status will be determined from bone marrow aspirates obtained at the 9‑month landmark and, when applicable, at other time points prior to disease progression. Quality‑of‑life and symptom scales will be administered at baseline and at subsequent visits, with time to confirmed deterioration defined by prespecified changes from baseline (≥16‑point increase for disease symptoms, ≥10‑point decrease for GHS/QoL or fatigue) confirmed on a later assessment. All time‑to‑event endpoints will be calculated from the date of enrollment (or from the date of first documented response for DOR) to the occurrence of the defined event or censoring. Data will be analyzed using appropriate statistical methods for proportion estimates, Kaplan‑Meier survival analyses, and longitudinal mixed‑effects models for patient‑reported outcomes.