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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Refractory Multiple Myeloma; Relapse Multiple Myeloma
• Intervention / Treatment: Drug: Talquetamab; Drug: Belantamab mafodotin; Drug: Pomalidomide

Detailed Description

After written informed consent is obtained from a participant, they will undergo screening evaluations within 28 days before first dose of study treatment, described above. Results from the disease assessments conducted within 28 days before Step-Up Dose 1 of study treatment performed as standard of care prior to screening may be used to fulfill screening requirements if all required assessments were collected.

Trial intervention will continue until progression of disease or drug discontinuation due to intolerable AEs. For participants in adequate response (Very Good Partial Response (VGPR) or better) after >6 cycles of therapy can change to maintenance Belantamab mafodotin and Pomalidomide. Participants who demonstrate sustained consecutive Measurable Residual Disease (MRD) negativity on separate bone marrow biopsies across > 1 year apart may hold all study related treatment but should continue monthly study assessments per the maintenance schedule of activities with the exception of the ocular exams. Duration of prophylaxis antimicrobial therapy can be determined by the treating physician but it is recommended to extend to at least 3 months after stopping study drug. Upon permanent discontinuation of trial intervention, each participant will be asked to undergo an end-of-treatment evaluation. 28 days after discontinuation of treatment, each participant will undergo a safety follow-up evaluation. Participants will then be contacted approximately every 2 months for long-term follow-up to assess survival status, receipt and type of subsequent anticancer therapy, and disease status. At end of trial enrollment, a long term overall survival follow-up is planned to be conducted.

Talquetamab (Tal) will be administered with step up dosing on day 1, 3, 5 with or without day 7 (dependent on target dose (TD) level of 0.4mg/kg or 0.8mg/kg) of Talquetamab. Two weeks after TD1, participants will enroll on Cycle 1, Day 1 of Tal (TD2) with Belantamab. Tal will subsequently be dosed every two weeks. Belantamab will be administered every 8 weeks on Day 1 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 Belantamab/Pomalidomide (Bela/Pom) maintenance. As stated above, patients who maintain MRD negativity for at least 1 year may also hold treatment.

The study will be conducted in 2 parts:

1. Part 1 Dose Escalation: Participants will be treated in cohorts with a BOIN design evaluating tolerability of Tal+Bela therapy at 3 planned dose levels including two intermediate levels of either Tal or Bela escalation. Titration will proceed until completion of DL3 or any pre-defined stopping criteria are met.
2. Part 2 Dose Expansion: Once the maximum tolerated dose (MTD) of combination therapy is determined, expansion cohorts of up to 12 participants will be enrolled across 2 dose levels to determine the optimal biological dose and confirm safety and secondary efficacy endpoints.

Dose limiting toxicities will be assessed during the first cycle of treatment.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: David R Levitz, MD; Phone Number: 7184508505; Email: dlevitz@montefiore.org
• Study Contact Backup: Name: Pinal R Ukani; Email: pukani@montefiore.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or Female subjects > 18 years of age

2. 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.

     1. Dose Expansion: Participants must have measurable disease by IMWG criteria.
3. 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.
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

5. Must have adequate organ and hematologic function as defined:

   1. 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)
   2. Hemoglobin > 8 g/dL.
   3. Platelet Count > 75 x10^9/L in the absence of transfusion support within 7 days.
   4. 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
6. 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])

7. 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.

   • A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions applies:

     • Is not a woman of childbearing potential (WOCBP) OR
     • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency during the intervention period and for at least 4 months after the last dose of study intervention, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
     • A WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours before dosing on Cycle 1 Day 1 and agree to use a highly effective method of contraception during the study and for 4 months after the last dose of belantamab mafodotin.
   • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

   • Nonchildbearing potential is defined as follows (by other than medical reasons):

     • ≥45 years of age and has not had menses for >1 year
     • Participants who have been amenorrheic for <2 years without history of a hysterectomy and oophorectomy must have a follicle-stimulating hormone value in the postmenopausal range upon screening evaluation.
     • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
   • Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

   • Male participants are eligible to participate if they agree to the following during the intervention period and for 6 months after the last dose of study treatment to allow for clearance of any altered sperm:

     • Refrain from donating sperm
     • PLUS either:
     • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR
     • Must agree to use contraception/barrier as detailed below:
     • Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of <1% per year, as when having sexual intercourse with a WOCBP (including pregnant females).
   • Contraceptive highly recommended during belantamab mafodotin studies*

   • Highly Effective Methods† That Have Low User Dependency

     • Implantable progestogen-only hormone contraception associated with inhibition of ovulation†
     • Intrauterine device (IUD)
     • Intrauterine hormone-releasing system (IUS)†
     • Bilateral tubal occlusion
     • Vasectomized partner
   • Note: Vasectomized partner is a highly effective contraceptive method provided that the partner is the sole sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method of contraception should be used. Spermatogenesis cycle is approximately 90 days.

   • Highly Effective Methods† That Are User Dependent

     • Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation‡

       • oral
       • intravaginal
       • transdermal
       • injectable

     • Progestogen-only hormone contraception associated with inhibition of ovulation

       • oral
       • injectable
   • Sexual abstinence
   • Note: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study intervention. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the participant.
   • *Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for those participating in clinical studies.
   • †Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those when used consistently and correctly.
   • ‡Male condoms must be used in addition to hormonal contraception. If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited to those that inhibit ovulation as the primary mode of action.
   • Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception for this study. Male condom and female condom should not be used together (due to risk of failure with friction).

Exclusion Criteria:

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:

1. Diagnosis of any of the following:

   1. Amyloidosis
   2. Plasma Cell Leukemia
   3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
   4. Myelodysplastic Syndrome, Myeloproliferative Neoplasia, or any other primary hematologic malignancy concurrent with Multiple Myeloma
   5. 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.

2. Treatment with any of the following:

   1. 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.
   2. Limited field radiotherapy < 7 days or extended field radiotherapy < 8 weeks prior to C1D1
   3. Major surgery < 4 weeks of the first dose of study drug on C1D1
   4. Any live or attenuated vaccines within 30 days of C1D1

3. 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.

4. Active central nervous system involvement of disease, unless they are clinically stable for > 4 weeks after completing treatment prior to screening (a brain and/or other anatomic regions with CNS involvement MRI within 1 month of enrollment is required).

   • Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs chemically related to belantamab mafodotin or any other components of the study treatment.

5. Any of the following cardiovascular events within 6 months prior to C1D1:

   1. Known heart failure with reduced left ventricular ejection fraction < 45%
   2. Congestive heart failure New York Heart Association Class III or IV
   3. Unstable angina pectoris
   4. Unstable symptomatic ischemic heart disease
   5. Myocardial infarction
   6. Uncontrolled hypertension despite appropriate medical therapy
   7. Ongoing symptomatic cardiac arrhythmias > grade 2
   8. Pulmonary embolism or cerebrovascular events
   9. Any other serious cardiac condition (e.g. pericardial effusion or restrictive cardiomyopathy)
   10. Evidence of current clinically significant untreated arrhythmias, including clinically significant electrocardiogram abnormalities such as second degree (Mobitz Type II) or third degree atrioventricular (AV) block.
6. History of autoimmune disease requiring systemic immunosuppressive therapy with daily dose of prednisone > 10mg or equivalent doses, or any other form of immunosuppressive therapy.

7. Any concurrent or uncontrolled medical, comorbid, or psychiatric condition that would, in the opinion of the investigator, limit compliance with study protocols.

   • Female subjects who are actively breastfeeding or pregnant on study start.
   • Presence of active renal condition (infection, requirement for dialysis, or any other condition that could affect participant's safety).
   • Active infection requiring treatment.
   • Evidence of active mucosal or internal bleeding.
   • Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice. NOTE: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
   • Current corneal epithelial disease except mild punctuate keratopathy.
   • Contact lenses are not allowed for participants while they are receiving belantamab mafodotin treatment. Contact lens use may be restarted after discontinuation of belantamab mafodotin treatment, provided the eye-care specialist confirms there are no other contraindications.
   • HIV considerations:

   • Participants with known HIV infection are excluded, unless the following criteria are met:

     • Established antiretroviral therapy (ART) for at least 4 weeks and HIV viral load <400 copies/mL
     • CD4+ T-cell (CD4+) counts ≥350 cells/µL
     • No history of AIDS-defining opportunistic infections within the last 12 months
   • Note: consideration must be given to ART and prophylactic antimicrobials that may have a drug: drug interaction and/or overlapping toxicities with belantamab mafodotin or other combination products as relevant.
   • Hepatitis B considerations:
   • Has documented presence of HBsAg and/or HBcAb at screening or within 3 months prior to the first dose of study intervention. Participants with hepatitis B will be excluded unless the following criteria can be met:

Serology: HBcAb+ HBsAg- Screening: HBV DNA undetectable During study treatment: Monitoring as per protocol • Antiviral prophylaxis must be given; choice of therapy as per local guidance

Serology: HBsAg+ at screening or within 3 months prior to first dose Screening: HBV DNA undetectable • Highly effective antiviral treatment started at least 4 weeks prior to first dose of study treatment • Baseline imaging per protocol • Participants with cirrhosis are excluded During study treatment: • Antiviral treatment maintained throughout study treatment • Monitoring and management as per protocol

• Hepatitis C considerations:
• Participants with a positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before first dose of study treatment are excluded unless the following conditions are met:
• Participants with a positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C RNA test is obtained.
• Positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months before first dose of study treatment unless the participant can meet the following criteria:
• RNA test negative
• Successful antiviral treatment (usually 8 weeks duration) is required, followed by a negative HCV RNA test after a washout period of at least 4 weeks.
• Note: Hepatitis RNA testing is optional and participants with a negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Talquetamab with Belantamab Dose Escalation and Expansion; 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; Talquetamab dosed at 0.4mg/kg or 0.8mg/kg every 2 weeks; Drug: Belantamab mafodotin; Belantamab mafodotin dosed at 1.4mg/kg or 1.9 mg/kg every 8 weeks; Drug: Pomalidomide; Pomalidomide dosed at 4mg Day 1- 21 of 28 day cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) including partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response (sCR)	Overall Response Rate (ORR) to treatment, defined as response to treatment as assessed by investigators using International Myeloma Working Group (IMWG) response criteria, will be tabulated. Point estimates and exact 95% confidence intervals for the percentage of participants achieving ORR will be calculated and summarized.	up to 2 years after discontinuation of treatment
Best Overall Response (BOR)	Best overall response (BOR) to treatment, defined as the best response to treatment from the start of study treatment until disease progression, as assessed by investigators using IMWG response criteria will be tabulated. Point estimates and exact 95% confidence intervals for the percentage of participants will be calculated and summarized.	up to 2 years after discontinuation of treatment
Duration of Response (DOR)	Duration of response to treatment, defined as the time from first evidence of response to earlier date of disease progression or death due to any cause, as assessed by investigators using IMWG response criteria, will be tabulated. Point estimates and exact 95% confidence intervals for the percentage of participants achieving ORR (PR, VGPR, CR, sCR) as well as MRD negativity rate will be calculated and summarized.	up to 2 years after discontinuation of treatment
Rate of Measurable Residual Disease negativity (MRD-) rate at 1 year	Rate of measurable residual disease negativity (MRD-), as assessed by investigators using IMWG response criteria, will be tabulated. Time-to-event endpoints will be estimated using Kaplan-Meier methods, if appropriate.	up to 1 year
Rate of sustained Measurable Residual Disease negativity (MRD-) rate at 1 year	Rate of sustained measurable residual disease negativity (MRD-), as assessed by investigators using IMWG response criteria, will be tabulated. Time-to-event endpoints will be estimated using Kaplan-Meier methods, if appropriate.	up to 1 year
Time to Progression (TTP)	Time to Progression defined as the duration of time from the start of treatment to the documentation of disease progression or recurrence. Time-to-event endpoints will be estimated using Kaplan-Meier methods, if appropriate.	up to 2 years after discontinuation of treatment
Time to Next Treatment (TTNT)	Time to Next Treatment (TTNT) defined as the duration of time from the start of one therapeutic treatment to a subsequent line of therapy. Time-to-event endpoints will be estimated using Kaplan-Meier methods, if appropriate.	up to 2 years after discontinuation of treatment
Time to Response (TTR)	Time to response (TRR), defined as the duration of time from the start of treatment to the first occurrence of disease response as assessed by investigators using IMWG response criteria, will be tabulated. Point estimates and exact 95% confidence intervals for the percentage of participants will be calculated and summarized.	up to 2 years after discontinuation of treatment
Progression Free Survival (PFS)	Progression free survival (PFS), defined as the length of time from the start of treatment until disease progression as assessed by investigators using IMWG response criteria, will be tabulated. Time-to-event endpoints will be estimated using Kaplan-Meier methods, if appropriate.	up to 2 years after discontinuation of treatment
Overall Survival (OS)	Overall survival (OS) defined as the time from the start of treatment until death from any cause, will be tabulated. Time-to-event endpoints will be estimated using Kaplan-Meier methods, if appropriate.	up to 2 years after discontinuation of treatment

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: David R Levitz, MD, Montefiore Medical Center

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 1, 2030
• Study Completion (Estimated): March 1, 2032

Study Registration Dates

• First Submitted: July 14, 2026
• First Submitted That Met QC Criteria: July 17, 2026
• First Posted (Actual): July 22, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Minimal Residual Disease; Very Good Partial Response
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Neoplastic Processes; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Neoplasm, Residual; Multiple Myeloma; pomalidomide; belantamab mafodotin; talquetamab
• Other Study ID Numbers: 2026-17651

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No