Clinical trial NCT06655818: Sub-study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Dostarlimab (GSK4057190) in Participants With RRMM
Official title: A Phase I/II, Randomized, Open-label Platform Study Utilizing a Master Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Anti-Cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)-DREAMM5. Sub-study 4 - Belantamab Mafodotin and Dostarlimab (GSK4057190) in Combination
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Multiple Myeloma
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-10-23
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose is to determine the safety and tolerability of belantamab mafodotin in combination with other anti-cancer treatments (in each sub-study), and to establish the recommended Phase 2 dose for each combination treatment to explore in the cohort expansion phase. This study is a sub study of the Master protocol (NCT04126200).


Eligibility criteria: Inclusion Criteria:

* Participant must be 18 years of age inclusive or older, at the time of signing the informed consent.
* Participants must have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the IMWG.
* Participants having at least 3 prior lines of prior anti-myeloma treatments including an immunomodulating agent (IMID) a proteasome inhibitor (PI) and an anti-CD38 monoclonal antibody.
* Participants with a history of autologous stem cell transplant are eligible for study participation when, transplant was \>100 days prior to study enrolment and with no active infection(s).
* Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, unless ECOG less than equal to (\<=)2 is due solely to skeletal complications and/or skeletal pain due to MM.
* Participants with measurable disease defined as at least one of the following: Serum M-protein greater than equal to (\>=)0.5 gram per deciliter (\>=5 gram per liter) or Urine M-protein \>=200 milligrams (mg) per 24 hours or Serum free light chain (FLC) assay: Involved FLC level \>=10 mg per deciliter (\>=100 mg per Liter) and an abnormal serum FLC ratio (\<0.26 or \>1.65).
* Participants who have tested positive for Hepatitis B core antibody (HBcAb) can be enrolled if the following criteria are met: Serology result HBcAb+, Hepatitis B surface antigen (HBsAg)-; HBV deoxyribonucleic acid (DNA) undetectable during screening.
* Participants who are currently receiving physiological doses oral steroids (\<10 mg/day), inhaled steroids or ophthalmological steroids.

Exclusion Criteria:

* Participants with current corneal epithelial disease except mild punctate keratopathy.
* Participants with evidence of cardiovascular risk.
* Participants with known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to belantamab mafodotin or any of the components of the study treatment. History of severe hypersensitivity to other mAb.
* Participants with active infection requiring antibiotic, antiviral, or antifungal treatment.
* Participants with other monoclonal antibodies within 30 days or systemic anti-myeloma therapy within \<14 days.
* Participants with prior radiotherapy within 2 weeks of start of study therapy.
* Participants with prior allogeneic transplant are prohibited.
* Participants who have received prior Chimeric Antigen T cell therapy (CAR-T) therapy with lymphodepletion with chemotherapy within 3 months of screening.
* Participants with any major surgery (other than bone-stabilizing surgery) within the last 30 days.
* Participants with prior treatment with an investigational agent within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter.
* Participants with \>=grade 3 toxicity considered related to prior check-point inhibitors and that led to treatment discontinuation.
* Participants who have received transfusion of blood products within 2 weeks before the first dose of study drug.
* Participants must not receive live attenuated vaccines within 30 days prior to first dose of study treatment or whilst receiving belantamab mafodotin +- partner agent in any sub-study arm of the platform trial and for at least 70 days following last study treatment.
* Participants with presence of active renal condition (infection, requirement for dialysis or any other condition that could affect participant's safety). Participants with isolated proteinuria resulting from MM.
* Participants with known human immunodeficiency virus (HIV) infection, unless the participant can meet all criteria: a) established anti-retroviral therapy for at least 4 weeks and HIV viral load\<400 copies/milliliter (mL) b) cluster of differentiation 4 plus (CD4+) T-cell (CD4+) counts \>= 350 cells/microliter (µL) c) No history of Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the last 12 months in which case the participant would be eligible for CE Phase only.
* Participants with autoimmune disease (current or history) or syndrome that required systemic treatment within the past 2 years.
* Exclusion for a recent (within the past 6 months) history of symptomatic pericarditis.
* Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
* Participants who have received prior therapy with an anti-programmed death-1 (anti-PD-1), anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent.
* Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. Use of inhaled steroids, local injection of steroids, and steroid eye drops are allowed.

Primary outcomes:
measure: DE Phase: Number of Participants With Dose Limiting Toxicities (DLT)
timeFrame: Up to 21 days
measure: DE Phase: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 153 weeks
measure: DE Phase: Number of Participants With Worst-Case Hematology Results by Maximum Grade Increase Post - Baseline Relative to Baseline
timeFrame: Baseline (Day 1) and up to 153 weeks
measure: DE Phase: Number of Participants With Worst-Case Chemistry Results by Maximum Grade Increase Post - Baseline Relative to Baseline
timeFrame: Baseline (Day 1) and up to 153 weeks
measure: CE Phase: Overall Response Rate (ORR)
timeFrame: Up to 26 weeks
Secondary outcomes:
measure: DE Phase: Overall Response Rate (ORR)
timeFrame: Up to 153 weeks
measure: CE Phase: Clinical Benefit Rate (CBR)
timeFrame: Up to 153 weeks
measure: DE Phase: Percentage of Participants Achieving Stringent Complete Response (SCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)
timeFrame: Up to 153 weeks
measure: CE Phase: Percentage of Participants Achieving SCR, CR, VGPR and PR
timeFrame: Up to 153 weeks
measure: DE Phase: Belantamab Mafodotin Concentrations for Plasma Antibody-Drug Conjugate (ADC)
timeFrame: Predose, end of infusion (EOI), 2, and 24 hours postdose on Cycle 1 Day 1, and at Cycle 1 Day 4, Day 8, Day 22, Predose and EOI on Cycle 2 Day 1, Cycle 4 Day 1, and at end of treatment (approximately 153 weeks)
measure: DE Phase: Belantamab Mafodotin Concentrations for Plasma Total Antibody
timeFrame: Predose, end of infusion (EOI), 2, and 24 hours postdose on Cycle 1 Day 1, and at Cycle 1 Day 4, Day 8, Day 22, Predose and EOI on Cycle 2 Day 1, Cycle 4 Day 1, and at end of treatment (approximately 153 weeks)
measure: DE Phase: Belantamab Mafodotin Concentrations for Plasma Cys-mcMMAF
timeFrame: Predose, end of infusion (EOI), 2, and 24 hours postdose on Cycle 1 Day 1, and at Cycle 1 Day 4, Day 8, Day 22, Predose and EOI on Cycle 2 Day 1, Cycle 4 Day 1, and at end of treatment (approximately 153 weeks)
measure: CE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC)
timeFrame: Up to 153 weeks
measure: CE Phase: Plasma Concentration of Belantamab Mafodotin Plasma Total Antibody
timeFrame: Up to 153 weeks
measure: CE Phase: Plasma Concentrations of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)
timeFrame: Up to 153 weeks
measure: DE Phase: Dostarlimab Concentration When Administered in Combination With Belantamab Mafodotin
timeFrame: Predose and end of infusion (EOI) on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, and at the end of treatment (approximately 153 weeks)
measure: CE Phase: Dostarlimab Concentration When Administered in Combination With Belantamab Mafodotin
timeFrame: Up to 153 weeks
measure: DE Phase: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin
timeFrame: Up to 153 weeks
measure: CE Phase: Number of Participants With Post-baseline Positive ADAs Against Belantamab Mafodotin
timeFrame: Up to 153 weeks
measure: DE Phase: Number of Participants With Post-baseline Positive ADAs Against Dostarlimab
timeFrame: Up to 153 weeks
measure: CE Phase: Number of Participants With Post-baseline Positive ADAs Against Dostarlimab
timeFrame: Up to 153 weeks
measure: DE Phase: Concentration of ADAs Against Dostarlimab When Administered in Combination With Belantamab Mafodotin
timeFrame: Up to 153 weeks
measure: CE Phase: Concentration of ADAs Against Dostarlimab When Administered in Combination With Belantamab Mafodotin
timeFrame: Up to 153 weeks
measure: DE Phase: Concentration of ADAs Against Belantamab Mafodotin
timeFrame: Up to 153 weeks
measure: CE Phase: Concentration of ADAs Against Belantamab Mafodotin
timeFrame: Up to 153 weeks
measure: DE Phase: Number of Participants With Adverse Events of Special Interest (AESI)
timeFrame: Up to 153 weeks
measure: CE Phase: Number of Participants With Adverse Events of Special Interest (AESI)
timeFrame: Up to 153 weeks
measure: DE Phase: Number of Participants With Any Corneal Event by Maximum Grade as Per CTCAE Grade
timeFrame: Up to 153 weeks
measure: CE Phase: Number of Participants With Any Corneal Events by Maximum Grade as Per CTCAE Grade
timeFrame: Up to 153 weeks
measure: CE Phase: Progression-free Survival (PFS)
timeFrame: Up to 153 weeks
measure: CE Phase: Duration of Response (DoR)
timeFrame: Up to 153 weeks
measure: CE Phase: Time to Response (TTR)
timeFrame: Up to 153 weeks
measure: CE Phase: Overall Survival (OS)
timeFrame: Up to 153 weeks
measure: CE Phase: Number of Participants With AEs and SAEs
timeFrame: Up to 153 weeks
measure: CE Phase: Number of Participants With AEs Leading to Discontinuation
timeFrame: Up to 153 weeks
measure: CE Phase: Number of Participants With Dose Reduction or Delay
timeFrame: Up to 153 weeks
measure: CE Phase: Number of Participants With Clinically Significant Changes in Hematology Lab Parameters
timeFrame: Up to 153 weeks
measure: CE Phase: Number of Participants With Clinically Significant Changes in Clinical Chemistry Lab Parameters
timeFrame: Up to 153 weeks
Other outcomes:
Locations:
city: Lille
country: France
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Ulsan
country: Korea, Republic of
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: