Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (DREAMM 5)

JRCT ID: jRCT2061230056

Registered date:12/09/2023

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Multiple Myeloma
• Date of first enrollment: 30/10/2023
• Target sample size: 464
• Countries of recruitment: Australia,Japan,Brazil,Japan,Canada,Japan,France,Japan,Germany,Japan,Greece,Japan,Republic of Korea,Japan,Mexico,Japan,Netherlands,Japan,Norway,Japan,Poland,Japan,Russian Federation,Japan,Spain,Japan,Sweden,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Dose Exploration(DE) Phase, Cohort Expansion(CE) Phase
Drug: Belantamab mafodotin
Drug: Nirogacestat
Drug: Lenalidomide
Drug: Dexamethasone

Outcome(s)

Primary Outcome

DE Phase
Number of participants achieving dose limiting toxicities (DLT)
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters

CE Phase
Overall Response Rate (ORR)

Secondary Outcome

DE Phase:
-ORR
-Number of participants achieving Partial Response (PR)
-Number of participants achieving Very Good Partial Response (VGPR)
-Number of participants achieving Complete Response (CR)
-Number of participants achieving stringent Complete Response (sCR)
-Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments
-Nirogacestat concentration when administered in combination with belantamab mafodotin
-Concentration of anti-drug antibodies (ADAs) against belantamab mafodotin when administered in combination
-Number of participants with adverse events of special interest (AESI) for belantamab mafodotin
-Number of participants with AESI for Nirogacestat
-Number of participants with abnormal ocular findings on ophthalmic examination

CE Phase:
-Clinical Benefit Rate (CBR)
-Number of participants achieving PR
-Number of participants achieving VGPR
-Number of participants achieving CR
-Number of participants achieving sCR
-Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments
-Nirogacestat concentration when administered in combination with belantamab mafodotin with anti-cancer treatments
-Concentration of ADAs against belantamab mafodotin when administered in combination with anti-cancer treatments
-Number of participants with AESI for belantamab mafodotin
-Number of participants with AESI for Nirogacestat
-Number of participants with abnormal ocular findings on ophthalmic examination
-Progression-free survival (PFS)
-Duration of response (DoR)
-Time to response (TTR)
-Overall survival (OS)
-Number of participants with AEs and SAEs
-Number of participants with AEs leading to discontinuation
-Number of participants with dose reduction or delay
-Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable

Include 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 immunodilating 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 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.

Exclude 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.

Related Information

• Primary Sponsor: Ishibashi Hideyasu
• Secondary ID(s): NCT04126200