TAlquetamab and BeLantamab Mafodotin in Relapsed/Refractory Multiple Myeloma (TaBleMM)

NCT07720843 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: 2026-17651
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 1, open-label dose escalation study evaluating the safety and clinical efficacy of Talquetamab in combination with Belantamab mafodotin for a time-limited interval followed by Belantamab mafodotin and Pomalidomide maintenance. The study will enroll subjects with Multiple Myeloma that have previously been treated with at least one prior line of therapy and have been treated with IMiDs, proteasome inhibitors, and anti-CD38 therapies either in combination or as single agent and are relapsed or are refractory to, or intolerant of, established therapies with clinical benefit in Multiple Myeloma. Talquetamab will be administered with step up dosing on day 1, 3, 5 with or without day 7 pending target dose (TD1) of Talquetamab (Tal) in dose level. Two weeks after TD1, patients will enroll on C1D1 of Tal (TD2) with Belantamab (Bela). Tal will subsequently be dosed every two weeks. Bela will be administered every 8 weeks on D1 of odd numbered cycles or until resolution of any ocular toxicities to grade 1 or better. After 6 cycles of induction, patients may transition to Bela/Pom maintenance.

Conditions

Relapse Multiple Myeloma; Refractory Multiple Myeloma

Keywords

Minimal Residual Disease; Very Good Partial Response

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of treatment emergent adverse events (TEAEs)

  Treatment-emergent adverse events (TEAEs) are defined as any adverse events (AEs) that begin or worsen on or after the start of study treatment through 28 days after the last dose of treatment drug. All AEs will be listed. Only TEAEs will be summarized. TEAEs will be summarized by Medical Dictionary for Regulatory Activities (version 23.1 or later) System Organ Class and Preferred Term. Separate tabulations will be produced for all TEAEs.

  Through the first 28 days of treatment

• Maximum tolerated dose (MTD)

  Maximum tolerated dose (MTD) is determined by the number of dose limiting toxicities (DLTs) during the first 28 days after the first administration of study treatment (Cycle 1) of each cohort. A DLT is defined as any adverse event (AE) that occurs during the DLT evaluation period which is considered related to study treatment, and also meets any of the criteria, as determined by the Data Safety Monitoring Committee (DSMC), with input from the clinical study team.

  Through the first 28 days of treatment (Cycle 1)

Secondary Outcomes (10)

• Overall Response Rate (ORR) including partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response (sCR)

  up to 2 years after discontinuation of treatment

• Best Overall Response (BOR)

  up to 2 years after discontinuation of treatment

• Duration of Response (DOR)

  up to 2 years after discontinuation of treatment

• Rate of Measurable Residual Disease negativity (MRD-) rate at 1 year

  up to 1 year

• Rate of sustained Measurable Residual Disease negativity (MRD-) rate at 1 year

  up to 1 year

Study Arms (1)

Talquetamab with Belantamab Dose Escalation and Expansion

EXPERIMENTAL

Dose Level 1- Talquetamab 0.4mg/kg q2weeks Belantamab Mafodotin 1.4mg/kg q8weeks Dose Level 2A- Talquetamab 0.8mg/kg q2weeks Belantamab Mafodotin 1.4mg/kg q8weeks Dose Level 2B- Talquetamab 0.4mg/kg q2weeks Belantamab Mafodotin 1.9mg/kg q8weeks Dose Level 3- Talquetamab 0.8mg/kg q2weeks Belantamab Mafodotin 1.9mg/kg q8weeks Talquetamab will be administered with step up dosing on day 1, 3, 5 with or without day 7 (dependent on target dose level of 0.4mg/kg or 0.8mg/kg) of Talquetamab. Two weeks after TD1, participants will enroll on C1D1 of Tal (TD2) with Belantamab. Tal will subsequently be dosed every two weeks. Belantamab will be administered every 8 weeks on D1 of odd numbered cycles or until resolution of any ocular toxicities to Grade 1 or better. After 6 cycles of induction, participants may transition to Bela/Pom maintenance. Patients who maintain MRD negativity for at least 1 year may also hold treatment.

Drug: Talquetamab; Drug: Belantamab mafodotin; Drug: Pomalidomide

Interventions

Talquetamab DRUG

Talquetamab dosed at 0.4mg/kg or 0.8mg/kg every 2 weeks

Talquetamab with Belantamab Dose Escalation and Expansion

Belantamab mafodotin DRUG

Belantamab mafodotin dosed at 1.4mg/kg or 1.9 mg/kg every 8 weeks

Talquetamab with Belantamab Dose Escalation and Expansion

Pomalidomide DRUG

Pomalidomide dosed at 4mg Day 1- 21 of 28 day cycles

Talquetamab with Belantamab Dose Escalation and Expansion

Eligibility Criteria

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

You may qualify if:

• Male or Female subjects \> 18 years of age
• Be willing and able to provide written informed consent prior to any protocol-related procedures including screening evaluations.
• Must meet 2014 International Myeloma Working Group (IMWG) guideline for diagnosis of Multiple Myeloma (and not smouldering myeloma) Dose Escalation: Participants in dose escalation must have measurable disease as defined by IMWG criteria, or have active bone findings on PET/CT or \>1 measurable plasmacytoma that can be monitored on other imaging modalities.
• Dose Expansion: Participants must have measurable disease by IMWG criteria.
• Have been previously treated with at least 1 prior line of MM therapy and have previously been exposed to an Immunomodulatory Drug (IMiD), PI, and CD38 either in combination or as single agents and are relapsed/refractory or intolerant of prior therapies.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Must have adequate organ and hematologic function as defined:
• Absolute Neutrophil Count (ANC) \> 1000 in the absence of growth factor support (granulocyte colony stimulating factor \[GSCF\] within 7 days or pegylated granulocyte colony stimulating factor \[peg-G-CSF\] within 14 days)
• Hemoglobin \> 8 g/dL.
• Platelet Count \> 75 x10\^9/L in the absence of transfusion support within 7 days.
• Aspartate aminotransferase (AST, SGOT) and alanine aminotransferase (ALT, SGPT) ≤2.5 × upper limit of normal (ULN); bilirubin ≤1.5 × ULN. Subjects with Gilbert's syndrome may have a bilirubin level \<3.0 × ULN
• Estimated glomerular filtration rate (eGFR) \> 30 as calculated by the Modified Diet in Renal Disease (MDRD) formula. All prior treatment-related toxicities (as defined by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] v6.0) must be \< Grade 1 at the time of enrollment, except for alopecia. Spot urine (albumin/creatinine ratios) \< 500 mg/g (56mg/mmol) OR urine dipstick Negative/trace (if \> + only eligible if confirmed \<500 mg/kg \[56mg/mmol\] by albumin/creatinine ratio \[spot urine from first void\])
• Sex and contraceptive/barrier requirements:
• Contraceptive use by male and female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this trial:
• A subject who meets any of the following criteria must not be enrolled on the study:
• Diagnosis of any of the following:
• Amyloidosis
• Plasma Cell Leukemia
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Myelodysplastic Syndrome, Myeloproliferative Neoplasia, or any other primary hematologic malignancy concurrent with Multiple Myeloma
• Any other history of malignancy other than Multiple Myeloma deemed at high risk of recurrence during study. Indolent cancers (e.g. prostate cancer without radiographic evidence of disease or history of resected local breast cancer on long term hormonal therapy) are acceptable.
• Treatment with any of the following:
• Systemic anticancer therapy \< 14 days prior to first dose of study related therapy (Step-Up Dose 1), or \<30 days for monoclonal antibodies (e.g. anti-CD38 antibodies). mAb for serious conditions unrelated to MM, such as COVID, may be permitted but need to be discussed with the medical monitor.
• Limited field radiotherapy \< 7 days or extended field radiotherapy \< 8 weeks prior to C1D1
• Major surgery \< 4 weeks of the first dose of study drug on C1D1
• Any live or attenuated vaccines within 30 days of C1D1
• History of refractoriness to Talquetamab or Belantamab mafodotin
• Participants who received \< 3 cycles of Talquetamab time limited therapy such as for bridging to other therapies without evidence of disease progression on treatment will be considered eligible after discussion with medical monitor.

Sponsors & Collaborators

• Montefiore Medical Center: lead
• GlaxoSmithKline: collaborator

Related Publications (7)

• Hungria V, Robak P, Hus M, Zherebtsova V, Ward C, Ho PJ, Ribas de Almeida AC, Hajek R, Kim K, Grosicki S, Sia H, Bryant A, Pitombeira de Lacerda M, Aparecida Martinez G, Sureda Balari AM, Sandhu I, Cerchione C, Ganly P, Dimopoulos M, Fu C, Garg M, Abdallah AO, Oriol A, Gatt ME, Cavo M, Rifkin R, Fujisaki T, Mielnik M, Pirooz N, McKeown A, McNamara S, Zhou X, Nichols M, Lewis E, Rogers R, Baig H, Eccersley L, Roy-Ghanta S, Opalinska J, Mateos MV; DREAMM-7 Investigators. Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2024 Aug 1;391(5):393-407. doi: 10.1056/NEJMoa2405090. Epub 2024 Jun 1.

  PMID: 38828933 BACKGROUND

• Dimopoulos MA, Beksac M, Pour L, Delimpasi S, Vorobyev V, Quach H, Spicka I, Radocha J, Robak P, Kim K, Cavo M, Suzuki K, Morris K, Pompilus F, Phillips-Jones A, Zhou XL, Fulci G, Sule N, Kremer BE, Opalinska J, Mateos MV, Trudel S; DREAMM-8 Investigators. Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma. N Engl J Med. 2024 Aug 1;391(5):408-421. doi: 10.1056/NEJMoa2403407. Epub 2024 Jun 2.

  PMID: 38828951 BACKGROUND

• Dimopoulos MA, Hungria VTM, Radinoff A, Delimpasi S, Mikala G, Masszi T, Li J, Capra M, Maiolino A, Pappa V, Chraniuk D, Osipov I, Leleu X, Low M, Matsumoto M, Sule N, Li M, McKeown A, He W, Bright S, Currie B, Perera S, Boyle J, Roy-Ghanta S, Opalinska J, Weisel K. Efficacy and safety of single-agent belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in patients with relapsed or refractory multiple myeloma (DREAMM-3): a phase 3, open-label, randomised study. Lancet Haematol. 2023 Oct;10(10):e801-e812. doi: 10.1016/S2352-3026(23)00243-0.

  PMID: 37793771 BACKGROUND

• Montes de Oca R, Alavi AS, Vitali N, Bhattacharya S, Blackwell C, Patel K, Seestaller-Wehr L, Kaczynski H, Shi H, Dobrzynski E, Obert L, Tsvetkov L, Cooper DC, Jackson H, Bojczuk P, Forveille S, Kepp O, Sauvat A, Kroemer G, Creighton-Gutteridge M, Yang J, Hopson C, Yanamandra N, Shelton C, Mayes P, Opalinska J, Barnette M, Srinivasan R, Smothers J, Hoos A. Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-mediated Antitumor Responses In Vivo. Mol Cancer Ther. 2021 Oct;20(10):1941-1955. doi: 10.1158/1535-7163.MCT-21-0035. Epub 2021 Jul 12.

  PMID: 34253590 BACKGROUND

• Tai YT, Mayes PA, Acharya C, Zhong MY, Cea M, Cagnetta A, Craigen J, Yates J, Gliddon L, Fieles W, Hoang B, Tunstead J, Christie AL, Kung AL, Richardson P, Munshi NC, Anderson KC. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014 May 15;123(20):3128-38. doi: 10.1182/blood-2013-10-535088. Epub 2014 Feb 25.

  PMID: 24569262 BACKGROUND

• Cohen YC, Magen H, Gatt M, Sebag M, Kim K, Min CK, Ocio EM, Yoon SS, Chu MP, Rodriguez-Otero P, Avivi I, Quijano Carde NA, Kumar A, Krevvata M, Peterson MR, Di Scala L, Scott E, Hilder B, Vanak J, Banerjee A, Oriol A, Morillo D, Mateos MV; RedirecTT-1 Investigators and Study Group. Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2025 Jan 9;392(2):138-149. doi: 10.1056/NEJMoa2406536.

  PMID: 39778168 BACKGROUND

• Trudel S, McCurdy A, Louzada ML, Parkin S, White D, Chu MP, Kotb R, Mian H, Othman I, Su J, Khan A, Gul E, Reece D. Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial. Nat Med. 2024 Feb;30(2):543-551. doi: 10.1038/s41591-023-02703-y. Epub 2024 Jan 4.

  PMID: 38177852 BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Neoplasm, Residual

Interventions

talquetamab; belantamab mafodotin; pomalidomide

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

Study Officials

• David R Levitz, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David R Levitz, MD

CONTACT

7184508505; dlevitz@montefiore.org

Pinal R Ukani

CONTACT

pukani@montefiore.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will be conducted in 2 parts: 1. Part 1 Dose Escalation: Subjects will be treated in cohorts with a Bayesian Optimal Interval (BOIN) design evaluating tolerability of Tal+Bela therapy at 3 planned dose levels; both Tal and Bela will be escalated in parallel. Titration will proceed until completion of DL3 or any pre-defined stopping criteria are met. 2. Part 2 Dose Expansion: Once the MTD of combination therapy is determined, expansion cohorts of up to 12 patients will be enrolled across 2 dose levels to determine the optimal biological dose and confirm safety and secondary efficacy endpoints.

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 22, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2032
• Last Updated: July 22, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share