Principal Investigator:Richardson, Paul, G
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.
- Participant must be 18 years of age inclusive or older, at the time of signing the
- 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 immunodilating agent (IMID) a proteasome inhibitor (PI) and an anti-CD38 monoclonal
- 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
- 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 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 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 and 7:
- Participants with contraception requirements specific to Sub-study 6 and 7
- Participants with platelets value for Adequate Organ System Function is ≥75 × 10^9/L.
- 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
- 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
- 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.
Additional Exclusion Criteria for Sub-study 1 and Sub-study 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:
- 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
- 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)
- 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
- 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 and 7:
- Participants with active or history of venous thromboembolism within the past 3
- 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:
- Participants who discontinued prior treatment with lenalidomide due to intolerable
Additional Exclusion Criteria for Sub-study 7:
- Participants who discontinued prior treatment with pomalidomide due to intolerable
Protocol #: 20-212