TAlquetamab and BeLantamab Mafodotin in Relapsed/Refractory Multiple Myeloma (TaBleMM)
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorMontefiore Medical Center
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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
Trial design
Design model
Sequential
Treatments tested in this trial
Talquetamab
DrugTalquetamab dosed at 0.4mg/kg or 0.8mg/kg every 2 weeks
Belantamab mafodotin
DrugBelantamab mafodotin dosed at 1.4mg/kg or 1.9 mg/kg every 8 weeks
Pomalidomide
DrugPomalidomide dosed at 4mg Day 1- 21 of 28 day cycles
Treatment groups
50 Participants
are divided into 1 treatment groupGroup A: Talquetamab with Belantamab Dose Escalation and ExpansionExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
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.
Time frame
Through the first 28 days of treatment2
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.
Time frame
Through the first 28 days of treatment (Cycle 1)Secondary outcomes
1
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.
Time frame
up to 2 years after discontinuation of treatment2
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.
Time frame
up to 2 years after discontinuation of treatment3
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.
Time frame
up to 2 years after discontinuation of treatment4
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.
Time frame
up to 1 yearLocations
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Montefiore Medical Center
Lead sponsor
GlaxoSmithKline
Collaborator
Source ClinicalTrials.gov
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