Last updated: 02/14/2025 18:00:07
Platform Study of Belantamab Mafodotin as Monotherapy and in Combination with Anti-cancer Treatments in Participants with Relapsed/Refractory Multiple Myeloma (RRMM)DREAMM5
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Recruitment complete
Recruitment complete
Trial overview
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) – DREAMM 5
Trial description: B-cell maturation antigen (BCMA) is a target present on tumor cells in participants with multiple myeloma. Belantamab mafodotin (GSK2857916); is an antibody-drug conjugate (ADC) containing humanized anti-BCMA monoclonal antibody (mAb). This is a phase I/II, randomized, open-label, platform study designed to evaluate the effects of belantamab mafodotin in combination with other anti-cancer drugs in participants with relapsed/refractory multiple myeloma. The Platform design incorporates a single master protocol, where multiple treatment combinations, as sub-studies, will be evaluated simultaneously.
Primary purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
DE Phase: Number of participants achieving dose limiting toxicities (DLT)
Timeframe: Up to 12 months
DE Phase: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Timeframe: Up to 12 months
DE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters
Timeframe: Up to 12 months
CE Phase: Number of participants achieving Overall Response Rate (ORR)
Timeframe: Up to 36 months
Secondary outcomes:
DE Phase: Number of participants achieving ORR
Timeframe: Up to 12 months
CE Phase: Number of participants achieving Clinical Benefit Rate (CBR)
Timeframe: Up to 36 months
DE Phase: Number of participants achieving Partial Response (PR)
Timeframe: Up to 12 months
CE Phase: Number of participants achieving PR
Timeframe: Up to 36 months
DE Phase: Number of participants achieving Very Good Partial Response (VGPR)
Timeframe: Up to 12 months
CE Phase: Number of participants achieving VGPR
Timeframe: Up to 36 months
DE Phase: Number of participants achieving Complete Response (CR)
Timeframe: Up to 12 months
CE Phase: Number of participants achieving CR
Timeframe: Up to 36 months
DE Phase: Number of participants achieving stringent Complete Response (sCR)
Timeframe: Up to 12 months
CE Phase: Number of participants achieving sCR
Timeframe: Up to 36 months
DE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments
Timeframe: Up to 12 months
CE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments
Timeframe: Up to 36 months
DE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin
Timeframe: Up to 12 months
CE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin
Timeframe: Up to 36 months
DE Phase: Feladilimab concentration when administered in combination with belantamab mafodotin
Timeframe: Up to 12 months
CE Phase: Feladilimab concentration when administered in combination with belantamab mafodotin
Timeframe: Up to 36 months
DE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin
Timeframe: Up to 12 months
CE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin
Timeframe: Up to 36 months
DE Phase: Dostarlimab concentration when administered in combination with belantamab mafodotin
Timeframe: Up to 12 months
CE Phase: Dostarlimab concentration when administered in combination with belantamab mafodotin
Timeframe: Up to 36 months
DE Phase: Isatuximab concentration when administered in combination with belantamab mafodotin
Timeframe: Up to 12 months
CE Phase: Isatuximab concentration when administered in combination with belantamab mafodotin
Timeframe: Up to 36 months
DE Phase: Concentration of anti-drug antibodies (ADAs) against belantamab mafodotin when administered in combination with anti-cancer treatments
Timeframe: Up to 12 months
CE Phase: Concentration of ADAs against belantamab mafodotin when administered in combination with anti-cancer treatments
Timeframe: Up to 36 months
DE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin
Timeframe: Up to 12 months
CE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin
Timeframe: Up to 36 months
DE Phase: Concentration of ADAs against feladilimab when administered in combination with belantamab mafodotin
Timeframe: Up to 12 months
CE Phase: Concentration of ADAs against feladilimab when administered in combination with belantamab mafodotin
Timeframe: Up to 36 months
DE Phase: Concentration of ADAs against dostarlimab when administered in combination with belantamab mafodotin
Timeframe: Up to 12 months
CE Phase: Concentration of ADAs against dostarlimab when administered in combination with belantamab mafodotin
Timeframe: Up to 36 months
DE Phase: Concentration of ADAs against isatuximab when administered in combination with belantamab mafodotin
Timeframe: Up to 12 months
CE Phase: Concentration of ADAs against isatuximab when administered in combination with belantamab mafodotin
Timeframe: Up to 36 months
DE Phase: Number of participants with adverse events of special interest (AESI) for belantamab mafodotin
Timeframe: Up to 12 months
CE Phase: Number of participants with AESI for belantamab mafodotin
Timeframe: Up to 36 months
DE Phase: Number of participants with AESI for GSK3174998
Timeframe: Up to 12 months
CE Phase: Number of participants with AESI for GSK3174998
Timeframe: Up to 36 months
DE Phase: Number of participants with AESI for Feladilimab
Timeframe: Up to 12 months
CE Phase: Number of participants with AESI for Feladilimab
Timeframe: Up to 36 months
DE Phase: Number of participants with AESI for Nirogacestat
Timeframe: Up to 12 months
CE Phase: Number of participants with AESI for Nirogacestat
Timeframe: Up to 36 months
DE Phase: Number of participants with AESI for Dostarlimab
Timeframe: Up to 12 months
CE Phase: Number of participants with AESI for Dostarlimab
Timeframe: Up to 36 months
DE Phase: Number of participants with AESI for Isatuximab
Timeframe: Up to 12 months
CE Phase: Number of participants with AESI for Isatuximab
Timeframe: Up to 36 months
DE Phase: Number of participants with abnormal ocular findings on ophthalmic examination
Timeframe: Up to 12 months
CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination
Timeframe: Up to 36 months
CE Phase: Number of participants achieving Progression-free survival (PFS)
Timeframe: Up to 36 months
CE Phase: Duration of response (DoR)
Timeframe: Up to 36 months
CE Phase: Time to response (TTR)
Timeframe: Up to 36 months
CE Phase: Number of participants achieving Overall survival (OS)
Timeframe: Up to 36 months
CE Phase: Number of participants with AEs and SAEs
Timeframe: Up to 36 months
CE Phase: Number of participants with AEs leading to discontinuation
Timeframe: Up to 36 months
CE Phase: Number of participants with dose reduction or delay
Timeframe: Up to 36 months
CE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters
Timeframe: Up to 36 months
Interventions:
Enrollment:
208
Primary completion date:
2029-12-02
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Multiple Myeloma
Product
Not applicable
Collaborators
Not applicable
Study date(s)
October 2019 to February 2029
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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 with current corneal epithelial disease except mild punctate keratopathy.
- Participants with evidence of cardiovascular risk.
Inclusion and exclusion 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 ophthalmalogical steroids. Inclusion Criteria Specific to Sub-study 6,7, and 8:
- Participants with contraception requirements specific to Sub-study 6, 7, and 8 respectively.
- Participants with platelets value for Adequate Organ System Function is ≥75 × 10^9/L. Inclusion Criteria Specific to Sub-study 8:
- In Japan, participants should reside in Japan and be Japanese as defined by having all biological Japanese grandparents. Similarly, in China, subjects should reside in China and be Chinese as defined by having all biological Chinese grandparents.
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. For participants receiving nirogacestat, HIV drugs that are strong Cytochrome P450 3A4 (CYP3A4) inhibitors are prohibited. HIV drugs that are moderate CYP3A4 inhibitors, while permitted, should be co-administered with caution and must be accompanied by nirogacestat dose modifications. Additional Exclusion Criteria for Sub-study 1 and 2:
- 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. Additional Exclusion Criteria for Sub-study 3, 6, 7, and 8:
- Participants with uncontrolled small and/or large intestinal disease.
- Participants with uncontrolled skin disease.
- Participants with any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement.
- Participants with previous administration of a gamma secretase inhibitor.
- Participants with concomitant administration of a strong CYP3A4 inhibitor or inducer. Additional Exclusion Criteria for Sub-study 4:
- 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. Additional Exclusion Criteria for Sub-study 5:
- Participants with Severe hypersensitivity to Isatuximab-irfc or to any of its excipients.
- Participants with prior treatment with other anti-CD38 monoclonal antibody within 6 months of the first dose of study drug treatment.
- Participants with known intolerance or hypersensitivity to infused proteins products, sucrose, histidine, and polysorbate 80. Additional Exclusion Criteria for Sub-study 6, 7, and 8:
- Participants with active or history of venous thromboembolism within the past 3 months.
- Participants with evidence of active mucosal or internal bleeding.
- Participants with contraindications to or are unwilling to undergo protocol-required anti-thrombotic prophylaxis or unable to tolerate antithrombolitic prophalaxis. Additional Exclusion Criteria for Sub-study 6 and 8:
- Participants who discontinued prior treatment with lenalidomide due to intolerable adverse events. Additional Exclusion Criteria for Sub-study 7:
- Participants who discontinued prior treatment with pomalidomide due to intolerable adverse events. Additional Exclusion Criteria for Sub-study 8:
- Pregnant or lactating female or female who are interrupting lactation.
- Previously diagnosed with interstitial lung disease or current complication of interstitial lung disease.
Trial location(s)
Showing 1 - 6 of 47 Results
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
Sub-study protocol summary
Available language(s): English
Sub-study results summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Study Results yet to be posted
Recruitment status
Recruitment complete
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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