This study will evaluate efficacy and tolerability various doses of belantamab mafodotin in combination with cevostamab and pomalidomide in patients with multiple myeloma who have relapsed disease after two or more lines of therapy and/or have refractory to treatment disease.
This is a phase Ib, multicenter, open-label study to evaluate the safety and efficacy various doses of belantamab mafodotin (belamaf) in combination with cevostamab and pomalidomide in patients with relapsed and/or refractory multiple myeloma (RRMM). The study consists of 2 parts. Part 1 will evaluate the clinical activity and safety of up to three dose combinations of belamaf and cevostamab in patients who have relapsed and refractory multiple myeloma after receiving 2 or more prior lines of therapy and having previously received lenalidomide, a proteosome inhibitor, and/or anti-CD38 mAb. Their disease must be refractory to the last line of therapy. The doses will be evaluated in cohorts: Cohort 1a - belamaf 1.9 mg/kg + cevostamab 90 mg; Cohort 1b - belamaf 1.9 mg/kg + cevostamab 160 mg; and Cohort 1c - belamaf 2.5 mg/kg + cevostamab 160 mg. In this part I the recommended phase 2 dose (RP2D) of the combination will be determined. Part 2 will evaluate the clinical activity and safety of the recommended phase 2 dose (RP2D) in patients who have relapsed multiple myeloma having previously received 1-3 prior line of therapy including lenalidomide, a proteosome inhibitor, and/or an anti-CD38 mAb. In addition, a cohort exploring the safety and efficacy of the combination of cevostamab and belamaf at the recommended phase 2 dose (RP2D) with low dose pomalidomide (2 mg ) will be considered. This study will have an induction phase (cycle 1-6) and a maintenance phase (cycle 7 onwards). Participants will receive study treatment until progression is documented. Participants will be followed for up to 24 months after confirmation of progressive disease or until death, whichever is reached earlier.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
108
Administered intravenously
Administered intravenously
Administered orally
Cross Cancer Institute
Edmonton, Alberta, Canada
QEII Health Sciences Centre
Halifax, Nova Scotia, Canada
London Health Sciences Centre
London, Ontario, Canada
The Ottawa Hospital - General Hospital
Ottawa, Ontario, Canada
Recommended Phase 2 Dose (RP2D)
The Recommended Phase 2 Dose (RP2D) will be determined based on the incidence of dose-limiting toxicities (DLTs), overall tolerability, and preliminary antitumor activity. DLTs will be evaluated based on adverse events, clinical assessments, and laboratory test results.
Time frame: From the first dose of study drugs until the end of 3 cycles of therapy (up to 9 weeks; each cycle is 21 days) in the last dose-escalation cohort, or until study therapy is discontinued due to disease progression or toxicity, whichever occurs first.
Overall Response Rate (ORR)
Overall Response Rate (ORR) is defined as the proportion of participants who achieved a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to International Myeloma Working Group (IMWG) criteria.
Time frame: From 3 weeks after the first dose of study therapy (end of Cycle 1; Cycle 1 is 21 days) until the date of documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.
Progression Free Survival (PFS)
Progression Free Survival (PFS) is defined as the time from the first dose of study treatment to the first documented disease progression or death from any cause, whichever occurs first.
Time frame: From the date of the first dose of study therapy until the date of documented disease progression or death from any cause, whichever occurs first, assessed up to 24 months.
Duration of Response (DOR)
Duration of Response (DOR) is defined as the time from the date of first documented partial response (PR) or better until documented disease progression or death from any cause, whichever occurs first.
Time frame: From the date of first documented partial response or better to the date of documented disease progression or death, whichever occurs first, assessed up to 24 months.
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UHN-Princess Margaret Cancer Centre
Toronto, Ontario, Canada
Hospital Maisonneuve - Rosemont
Montreal, Quebec, Canada
McGill University Health Centre -MUHC
Montreal, Quebec, Canada
Overall Survival (OS)
Overall Survival (OS) is defined as the time from the first dose of study treatment to death from any cause.
Time frame: From the date of the first dose of therapy until the date of death from any cause, assessed up to 24 months.
Rates of Corneal Adverse Events
The proportion of participants experiencing corneal adverse events, including a decrease in best corrected visual acuity (\>20/50) in both eyes at the same time, at the recommended dose of belamaf in combination with cevostamab.
Time frame: From 1 day before receiving belamaf until the end of treatment or, if corneal findings are present, until corneal findings return to pre-treatment (baseline) condition or become stable, assessed up to 12 months.
Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs)
An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non- investigational) product, whether or not related to that medicinal (investigational) product. A SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event that may require medical or surgical intervention, results in a second malignancy.
Time frame: From 1 day before receiving study therapy until death from any cause or 90 days after discontinuation of study therapy, whichever occurs first.
Number of Adverse Events of Special Interest (AESI)
* Any grade ≥2 CRS (Cytokine Release Syndrome) * Any suspected or confirmed HLH/IEC-HS (Hemophagocytic Lymphohistiocytosis/ Immune Effector Cell-Associated HLH-Like Syndrome) * Any grade ICANS (Immune effector cell-associated neurotoxicity syndrome) * Grade 4 Corneal AEs (Adverse Events) * Grade ≥ 3 infections * Grade ≥ 2 Infusion Related Reactions
Time frame: From 1 day before receiving the study therapy until the date of death from any cause or 90 days following last date of study therapy, whichever occurs first.
Change from Baseline in Health-Related Quality of Life as Assessed by EORTC QLQ-C30
Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), a 30-item cancer-specific questionnaire. Scores range from 0 to 100, with higher scores on the Global Health Status/Quality of Life scale indicating better health-related quality of life.
Time frame: From 1 day before receiving study therapy to the end of study treatment, including the last day of treatment, assessed up to approximate 73 months.
Change From Baseline in Patient-Reported Outcomes as Assessed by PRO-CTCAE
Patient-reported outcomes will be assessed using selected Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) to assess toxicities of interest, including neurological symptoms (numbness, tingling, dizziness) and visual symptoms (blurred vision, flashing lights, visual floaters and watery eyes).
Time frame: From 1 day before receiving study therapy to the end of study treatment, including the last day of treatment, assessed up to approximate 73 months.