A Phase II Study of Teclistamab Combined with Autologous Lymphocyte Infusion in Relapsed/Refractory Multiple Myeloma

Trial ID: 2025-521827-61-00
Protocol: MM0125
Sponsor: Fondazione Gimema Franco Mandelli Onlus

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Diseases & Conditions

Plasma cell myeloma refractory

Objectives

The primary objective is to assess the efficacy of teclistamab combined with autologous lymphocyte infusion in patients with relapsed/refractory multiple myeloma, measured by Duration of Response. Secondary objectives include evaluation of response according to International Myeloma Working Group criteria, determination of Progression‑Free Survival, assessment of Overall Survival, characterization of the safety profile, and conduct of biologic ancillary studies to explore correlative biomarkers.

Participants

The sponsor did not provide information on the total number of participants. The study population comprised adult patients aged 18 years and older, including both male and female individuals, with a confirmed diagnosis of multiple myeloma that was refractory or relapsed according to WHO 2022 classification and International Myeloma Working Group criteria. Eligible participants demonstrated measurable disease, an Eastern Cooperative Oncology Group performance status of ≤2, and a life expectancy of at least 2 months. Inclusion required specific laboratory parameters (e.g., lymphocyte count ≥0.3 × 10⁹/L, platelet count >50 × 10⁹/L, creatinine clearance ≥30 mL/min), prior exposure to one or two lines of therapy including an IMID, a PI, and an anti‑CD38 antibody, and successful collection of autologous lymphocytes. Women of childbearing potential needed a recent negative pregnancy test. Selection was based on these clinical and laboratory criteria; no specific lifestyle requirements such as diet or physical activity were stipulated.

Plans and Procedures

The TALIM study is a phase II interventional trial evaluating the combination of TECLISTAMAB subcutaneous injection and autologous lymphocyte infusion in adults with relapsed/refractory multiple myeloma. The overall study period extends from May 31 2026 to May 31 2030, with each participant expected to remain in the trial for approximately 24 months. After obtaining informed consent, a screening visit collects eligibility data, confirms disease status, and ensures successful collection of ≥100 × 10⁶ /kg autologous lymphocytes. The baseline (day 1 of cycle 1) visit initiates TECLISTAMAB at the protocol‑specified dose, followed by the first lymphocyte infusion. Subsequent study visits occur at the start of each treatment cycle to administer TECLISTAMAB, monitor safety, and assess disease response; specific efficacy assessments are performed at cycle 5 and every three cycles thereafter according to IMWG criteria. The primary endpoint, estimation of Duration of Response at 18 months from combination therapy (24 months from TECLISTamab initiation), is complemented by secondary endpoints including progression‑free survival, overall survival, and safety evaluations (CRS and ICANS). The end‑of‑study visit is scheduled at 24 months or earlier if any of the following occur: confirmed disease progression, unacceptable toxicity, withdrawal of consent, or inability to comply with protocol requirements, at which point participants discontinue study treatment.

Treatment

The experimental agent teclistamab is administered as a subcutaneous injection at a dose of 3 mg/kg. The injection is given according to the protocol‑defined schedule, with each dose delivered on a weekly basis during the initial treatment phase and subsequently spaced to every two weeks contingent on response assessment.

A second dose tier of the investigational medication comprises subcutaneous administration of teclistamab at 0.3 mg/kg. This lower dose follows the same administration route and frequency as the higher dose tier, allowing for dose‑adjustment based on safety and pharmacodynamic criteria.

The study also includes autologous lymphocytes infusion (ALI) as a non‑experimental component. Autologous lymphocytes are collected from each participant, processed according to Good Manufacturing Practice standards, and reinfused intravenously following a predefined schedule that aligns with the teclistamab dosing regimen.

All administrations are performed by qualified clinical personnel. Compliance with the dosing schedule is monitored through documented injection logs, electronic case report forms, and periodic review of infusion records. Dose modifications, interruptions, or discontinuations are recorded in accordance with the protocol’s safety management guidelines.

Efficacy

Efficacy will be evaluated by estimating the Duration of Response at 18 months after the combination of teclistamab and autologous lymphocyte infusion (which corresponds to 24 months from the start of teclistamab monotherapy). The estimation will be based on longitudinal response assessments performed throughout the treatment period.

Secondary efficacy assessments comprise response determination at cycle 5 and thereafter every three cycles according to the International Myeloma Working Group (IMWG criteria) response definitions, evaluation of Progression‑Free Survival at 18 months from therapy initiation, and measurement of Overall Survival at 24 months from therapy initiation.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Patient has a confirmed diagnosis of MM according to the WHO 2022 classification (18)
Patient age is ≥ 18 years of age
Patient has a relapsed or refractory disease as defined below: 1.Relapsed disease is defined as an initial response to previous treatment, followed by confirmed progressive disease by the International Myeloma Working Group (IMWG) (15) criteria >60 days after cessation of treatment 2. refractory disease is defined as failure to achieve a response or confirmed progressive disease by IMWG criteria (15) during previous treatment or ≤60 days after cessation of treatment
Previous treatment with 1 or 2 lines of treatment (induction plus autologous stem cell transplant plus consolidation and maintenance has to be considered one single line)
Previous triple exposure that included an IMID, a PI, and an anti-CD38 antibody (patients with no response or relapse after front line therapy with Dara-VTD or Dara-VRD are eligible)
Progressive active symptomatic disease
Patient has measurable disease as defined by any of the following: Serum M-protein level ≥0.5 g/dL; or Urine M-protein level ≥200 mg/24 hours; or Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
Able to adhere to the study visit schedule and all the other protocol procedures and requirements
Patient has the following laboratory parameters: 1.Total lymphocytes count ≥ 0.3 x 109 /L 2.Platelet count > 50 x 109 /L unless due to bone marrow involvement by MM 3.Conjugated bilirubin up to 2 x ULN unless due to liver involvement by MM 4. Alkaline phosphatase and transaminases up to 2 x ULN unless due to liver involvement by MM 5.Creatinine clearance ≥ 30 ml/min
A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test within 2-7 days prior to C1D1
Life expectancy ≥ 2 months
Successful collection of at least 100 x 106 /kg autologous lymphocytes before starting treatment with Te.
Patient understands and voluntarily signs an informed consent form.

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Exclusion Criteria

Previous treatment with > 2 lines of therapy
Patient has active central nervous system involvement with MM
Received any prior BCMA-directed therapy
Received the following prior antimyeloma therapy, within the specified time frame prior to enrollment: 1.Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or ≥5 half-lives, whichever is less 2.Investigational vaccine within 4 weeks 3.Monoclonal antibody therapy wihin 21 days 4.Cytotoxic therapy within 21 days 5.PI therapy within 14 days 6.IMiD agent therapy within 14 days 7.Radiotherapy within 14 days or focal radiation within 7 days.
Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells) within 3 months
Stem cell transplant: 1.previous allogeneic stem cell transplant 2.autologous stem cell transplant performed within 12 weeks
Patients with plasma cell leukemia (presence of 5% or more plasma cells in conventional peripheral blood smear white blood cell differential count)
Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients
Any ongoing myelodysplastic syndrome or B-cell malignancy (other than MM)
Any history of malignancy, other than MM, which is considered at high risk of recurrence requiring systemic therapy
Any active malignancy (ie, progressing/requiring treatment change in the last 24 months) other than MM. The only allowed exceptions are malignancies treated within the last 24 months that are considered cured: 1.Non-muscle invasive bladder cancer (solitary Ta-PUNLMP or low grade, <3 cm, no CIS) 2.Non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection 3.Non-invasive cervical cancer 4.Breast cancer: treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer (anti-hormonal therapy is permitted) 5.Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally(RP/RT/focal treatment) 6.Other malignancy considered cured with minimal risk of recurrence in consultation with physician.
Clinically relevant and active liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
Patient has any other concurrent severe and/or uncontrolled medical condition(s) (e.g., uncontrolled diabetes mellitus, uncontrolled hypertension, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), active hemorrhage, psychiatric illness, active or uncontrolled infection that in the investigator opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form
Participant had major surgery or had significant traumatic injury within 2 weeks prior to enrollment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study
Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrollment
Patient has a known history of HIV seropositivity
Seropositive for hepatitis B: defined by a positive test for HbsAg. Participants with resolved infection (ie, participants who are HbsAg negative with antibodies to total anti-HBc with or without the presence of anti-HBs) must be screened using RT-PCR measurement of HBV DNA levels. Participants with a known history of HBV infection must be screened using RT-PCR measurement of HBV DNA levels irrespective of serological results. Those who are RT-PCR positive will be excluded. Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by RT-PCR (see Appendix 12)
Active hepatitis C infection as measured by positive HCV-RNA testing. Participants with a history of HCV antibody positivity must undergo HCV-RNA testing. If a participant with history of chronic hepatitis C infection (defined as both HCV antibody and HCV-RNA positive) completed antiviral therapy and has undetectable HCV-RNA 12 weeks following the completion of therapy, the participant is eligible for the study.