Phase II Open‑Label Multicenter Study of Teclistamab + Pomalidomide in Relapsed/Refractory Multiple Myeloma after 1–3 Prior Lines including Lenalidomide and Anti‑CD38

The primary objective is to assess the efficacy of teclistamab combined with pomalidomide administered in an alternate mode in participants with RRMM who have received 1–3 prior lines of therapy, including lenalidomide and anti‑CD38 therapy, to determine therapeutic benefit in this heavily pretreated population. Secondary objectives include:

• Further comparison of efficacy of the combination in the alternate administration schedule.
• Assessment of the safety profile of the combination.
• Evaluation of participants’ symptoms, functioning, and health‑related quality of life.
• Quantitative and qualitative analysis of the T‑cell compartment and spatial characteristics of the tumor microenvironment using flow cytometry, NGS methylation detection, spatial transcriptomics, and ELISPOT for antiviral T‑cell responses.

The trial enrolled adult patients (≥ 18 years) of both sexes with a diagnosis of multiple myeloma that was relapsed or refractory after 1–3 prior antimyeloma regimens, including a minimum of two cycles of an anti‑CD38 monoclonal antibody and two cycles of lenalidomide. Eligible participants were required to have measurable disease (serum M‑protein ≥ 0.5 g/dL or serum free light chain ≥ 10 mg/dL with an abnormal κ/λ ratio), an ECOG performance status of 0–2, and laboratory values within predefined safety thresholds (e.g., hemoglobin ≥ 8.0 g/dL, platelets ≥ 50–75 × 10⁹/L, ANC ≥ 1.0 × 10⁹/L, AST/ALT ≤ 2.5 × ULN, eGFR ≥ 30 mL/min). Lifestyle considerations included adherence to contraception requirements for participants of childbearing potential, abstention from sperm or egg donation during the study and for a defined period afterward, and compliance with protocol‑specified dietary and activity restrictions. The sponsor did not provide information on the total number of participants enrolled.

The study is a Phase II, open‑label, multicenter trial evaluating the combination of subcutaneous teclistamab and oral pomalidomide in participants with relapsed/refractory multiple myeloma who have received 1–3 prior lines of therapy, including lenalidomide and an anti‑CD38 antibody. Eligible adults undergo a screening visit to confirm diagnosis, measurable disease, performance status, and laboratory criteria; following informed consent, participants receive an initial loading dose of teclistamab (1 mg/kg) followed by weekly subcutaneous administrations, and daily oral pomalidomide (1 mg) in an alternating cycle schedule. Study visits are scheduled at baseline (day 1), then every 28 days for safety assessments, efficacy evaluations, and pharmacovigilance, with additional visits at the end of each treatment cycle to record response, adverse events, and quality‑of‑life measures. The primary efficacy endpoint, progression‑free survival at 12 months (12 cycles), is assessed at the 12‑cycle visit, while secondary endpoints—including MRD negativity, overall response rate, overall survival, and safety parameters—are evaluated at 12‑ and 24‑cycle visits and during long‑term follow‑up. Participants remain in the trial for up to 24 months of treatment plus a follow‑up period until the study end date (estimated 2031‑10‑27). Early termination may occur if a participant experiences disease progression, grade 3–4 toxicity not manageable with protocol‑specified interventions, withdrawal of consent, or other investigator‑determined safety concerns.

The investigational agent teclistamab is supplied as a solution for injection intended for subcutaneous administration. Each dose consists of 1 mg per kilogram of body weight, delivered as a single subcutaneous injection. The dosing schedule follows the protocol‑specified intervals, and the product is administered in a sterile manner by qualified personnel.

The companion investigational drug, pomalidomide, is provided in hard capsules containing 2 mg of active substance; the protocol specifies a dose of 1 mg per administration. Capsules are taken orally in accordance with the study schedule. Compliance with oral dosing is assessed by capsule count and patient diary entries.

Both agents are administered concomitantly as defined by the study protocol. Dosing cycles are initiated after verification of eligibility criteria and continue until disease progression, unacceptable toxicity, or study termination. Participant adherence is monitored through scheduled clinic visits, injection site assessments, and review of medication logs. Any missed or delayed doses are documented and reported per regulatory requirements.

Efficacy will be evaluated primarily by assessing progression‑free survival at 12 months (corresponding to 12 treatment cycles). Secondary efficacy assessments include determination of minimal residual disease (MRD) negativity combined with complete response (CR) after 12 and 24 cycles, overall progression‑free survival, overall response rate (partial response or better), very good partial response or better, CR or better, duration of response, time to response, overall survival, and changes from baseline in symptoms, functioning, and health‑related quality of life. Additional secondary measures comprise time to worsening of symptoms, functioning, and quality of life, as well as incidence and severity of adverse events, including grade 3–4 infections, serious adverse events, grade 5 events/deaths, and events leading to treatment withdrawal or hospitalization.

These efficacy parameters will be measured at predefined timepoints, notably at the end of cycle 12 and cycle 24 for MRD and CR assessments, and at regular intervals throughout treatment for response rates, survival outcomes, and patient‑reported outcomes. Data collection will follow the study protocol schedule, and analyses will be performed in accordance with standard statistical methods for time‑to‑event and proportion endpoints.