A Study Comparing Treatment With Teclistamab and Talquetamab Versus Daratumumab and Lenalidomide in Patients With Multiple Myeloma After Stem Cell Transplant Who Still Have Detectable Disease

NCT07740486 | Not Yet Recruiting Phase 3 DMC

• 4 other identifiers: PMC0112024/ABM/02/0000464407564MMY30112025-525097-11-00
• Study Type: interventional
• Target: 248
• Locations: 0 countries
• Sites: N/A

Brief Summary

Multiple myeloma is a type of blood cancer that can come back even after effective treatment. After high-dose therapy and autologous stem cell transplantation (ASCT), some patients have no visible signs of disease, but small numbers of cancer cells may still remain in the body. This is called measurable residual disease (MRD). These remaining cells may lead to disease relapse. The purpose of this study is to find out whether a new maintenance treatment can eliminate these remaining cancer cells more effectively than the current standard treatment. More effective maintenance therapy may help reduce the risk of disease progression and improve long-term outcomes for patients. This study, called TiTan, is a phase III, multicenter clinical trial conducted in Poland. It will include 248 adult patients with newly diagnosed multiple myeloma who have undergone ASCT, have no signs of disease progression, but still have detectable MRD. Participants will be randomly assigned (by chance) to one of two treatment groups. Neither the patient nor the doctor can choose the group. In the experimental group, patients will receive two immunotherapy medicines, teclistamab and talquetamab. If MRD becomes undetectable after the protocol-defined period, treatment may be stopped and the patient will continue under observation. In the standard treatment group, patients will receive daratumumab and lenalidomide, which are commonly used maintenance treatments. The duration and adjustments of treatment may depend on MRD results. The main goal of the study is to determine how many patients achieve undetectable MRD after 12 months of treatment together with a complete response to therapy. This will show whether the new treatment is more effective in removing residual cancer cells. The study will also evaluate how long patients live without disease progression, overall survival, treatment safety, and the impact of treatment on patients' daily functioning and quality of life. In addition, researchers will assess whether achieving undetectable MRD leads to better long-term outcomes. Patient safety will be closely monitored throughout the study. Participants will undergo regular medical check-ups, including blood tests, bone marrow tests, and imaging studies. All side effects will be carefully recorded and assessed according to international standards. Patients may withdraw from the study at any time without giving a reason. This non-commercial study aims to improve knowledge about maintenance treatment in multiple myeloma after ASCT and may help support future treatment decisions for patients with this disease.

Conditions

Multiple Myeloma (MM)

Keywords

Multiple Myeloma; Maintanance Therapy; Measurable residual disease; Autologous stem cell transplantation; Bispecific antibodies; Bone marrow disease assessment

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Achieving MRD Negativity With Complete Response

  The proportion of participants achieving measurable residual disease negativity at a sensitivity level of 10\^-5 together with complete response, assessed according to International Myeloma Working Group (IMWG) criteria at the specified timepoint.

  At Month 12

Secondary Outcomes (10)

• Progression-Free Survival

  Through study completion, up to approximately 36 months after enrollment of the last participant

• Change From Baseline in Global Health Status and Functional Scales Assessed by EORTC QLQ-C30

  From baseline through study completion (up to approximately 36 months after enrollment of the last participant)

• Change From Baseline in Multiple Myeloma-Specific Quality of Life Assessed by EORTC QLQ-MY20

  From baseline through study completion (up to approximately 36 months after enrollment of the last participant)

• Overall Survival

  Through study completion, up to approximately 36 months after enrollment of the last participant

• Proportion of Participants Achieving Complete Response or Better

  Through study completion, up to approximately 36 months after enrollment of the last participant

Study Arms (2)

Arm A (Tec-Tal)

EXPERIMENTAL

Participants receive maintenance therapy with teclistamab in combination with talquetamab. The study evaluates whether maintenance treatment with dual immunotherapy can improve eradication of measurable residual disease in participants with newly diagnosed multiple myeloma who remain MRD-positive after autologous stem cell transplantation. Treatment is administered according to protocol-defined procedures, and participants are followed for assessment of efficacy and safety outcomes.

Drug: Teclistamab; Drug: Talquetamab

Arm B (Dara-R)

ACTIVE COMPARATOR

Participants receive maintenance therapy with daratumumab and lenalidomide. This treatment regimen represents the comparator maintenance strategy for participants with newly diagnosed multiple myeloma who remain MRD-positive after autologous stem cell transplantation. Treatment is administered according to protocol-defined procedures, and participants are followed for assessment of efficacy and safety outcomes.

Drug: Daratumumab (Subcutaneously); Drug: Lenalidomide

Interventions

Teclistamab DRUG

Teclistamab is administered as part of combination immunotherapy according to protocol-defined dosing and schedule in participants receiving maintenance treatment for multiple myeloma.

Arm A (Tec-Tal)

Talquetamab DRUG

Talquetamab is administered in combination with teclistamab as part of maintenance immunotherapy according to protocol-defined dosing and schedule.

Arm A (Tec-Tal)

Daratumumab (Subcutaneously) DRUG

Daratumumab is administered as part of standard maintenance therapy according to protocol-defined dosing and schedule in participants with multiple myeloma.

Arm B (Dara-R)

Lenalidomide DRUG

Lenalidomide is administered as continuous maintenance therapy according to protocol-defined dosing and schedule in combination with daratumumab.

Arm B (Dara-R)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented diagnosis of MM as per IMWG diagnostic criteria.
• Newly diagnosed patients who have completed a single or tandem autologous stem cell transplant after receiving quadruplet induction (containing an anti-CD38 antibody, an immunomodulatory drug, and a proteasome inhibitor). Up to 2 cycles of post-ASCT consolidation are acceptable.
• Patients must have received high-dose chemotherapy and a first ASCT within 12 months from the initiation of induction therapy.
• Patients must be within 6 months of their most recent ASCT, or within 7 months for patients who received consolidation therapy.
• Positive minimal residual disease (at a 10-⁵ threshold) in the bone marrow assessed by NGF after autologous stem cell transplantation (assessed 60 to 150 days after transplantation and after completion of any consolidation therapy, with the assessment used for eligibility performed prior randomization).
• Males or females ≥ 18 years of age
• Karnofsky performance status score ≥ 50% ( ECOG performance status score of ≤2).
• Adequate hepatic function, with bilirubin ≤ 2.0 x ULN - except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤ 1.5 ULN is required) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN.
• ANC ≥ 1.0 x 109/L (prior growth factor support is permitted but must be without support for 7 days for G-CSF or GM-CSF or 14 days for pegylated-G-CSF), hemoglobin ≥ 8 g/dL (without red blood cell transfusion in the prior 7 days; recombinant human erythropoietin use is permitted), Platelets ≥75×109/L in patients in whom \<50% of bone marrow nucleated cells are plasma cells and ≥50×109/L in patients in whom ≥50% of bone marrow nucleated cells are plasma cells (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test)
• Calculated creatinine clearance (by Cockcroft-Gault) ≥ 30 ml/min or creatinine clearance measured by a 24-hour urine collection.
• Serum calcium corrected for albumin ≤ 14 mg/dl or free ionized calcium \<6.5 mg/dL.
• Females of childbearing potential (FCBP) must have 2 negative pregnancy tests (sensitivity of at least 50 mIU/mL) prior to initiating treatment. The first pregnancy test must be performed within 10-14 days before and the second pregnancy test must be performed within 24 hours before the drugs are administered.
• Females of childbearing potential must agree to use a highly effective method of contraception (failure rate \<1% per year), preferably with low user dependency, throughout the study treatment period and for at least 6 months after the last dose of study treatment.
• Male participants must agree to use a condom during sexual intercourse with a pregnant woman or a woman of childbearing potential during study treatment and for at least 90 days after the last dose of study treatment. In addition, male participants must ensure that their partner of childbearing potential uses effective contraception, (failure rate \<1% per year), preferably with low user dependency, during the same period.
• Voluntary written informed consent.

You may not qualify if:

• Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the NCI CTCAE Version 5.0.
• COPD with a FEV1 \<50% of predicted normal. Note that FEV1 testing is required for participants with known or suspected of having COPD or asthma and participants must be excluded if FEV1 \<50% of predicted normal.
• Severe persistent asthma within the past 2 years (see Appendix x\[DS2.1\] \[for severity of Asthma\]), uncontrolled asthma of any classification. Note that FEV1 testing is required for participants known or suspected asthma and participants must be excluded if FEV1 \<50% of predicted normal.
• CNS involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required.
• Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary light chain amyloidosis.
• Any ongoing myelodysplastic syndrome or B cell malignancy (other than multiple myeloma).
• Any history of malignancy, other than multiple myeloma, which is considered at high risk of recurrence requiring systemic therapy.
• Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than multiple myeloma. The only allowed exceptions are malignancies treated within the last 24 months that are considered cured:
• Non-muscle invasive bladder cancer (solitary Ta-PUNLMP or low grade, \<3 cm, no CIS).
• Non-melanoma skin cancers treated with curative therapy or localized melanoma treated with curative surgical resection alone
• Noninvasive cervical cancer
• Localized prostate cancer (M0, N0) with a Gleason Score ≤7a, treated locally only (radical prostatectomy/radiation therapy/focal treatment)
• Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer (antihormonal therapy is permitted)
• Other malignancy that is considered cured with minimal risk of recurrence in consultation with the Sponsor
• Stroke, transient ischemic attack, or seizure within 6 months prior to signing ICF.

Sponsors & Collaborators

• Polish Myeloma Consortium: lead
• Medical Research Agency, Poland: collaborator
• Johnson & Johnson: collaborator

MeSH Terms

Conditions

Multiple Myeloma; Neoplasm, Residual

Interventions

talquetamab; daratumumab; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Dominik Dytfeld, Professor

CONTACT

+48 61 854 95 71; dytfeld@me.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2026
• First Posted: July 31, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): April 1, 2033
• Last Updated: July 31, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share