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

Multiple Myeloma Clinical Trial

— DREAMM5  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04126200
• Other study ID #: 208887
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 7, 2019
• Est. completion date: February 12, 2029

Study information

• Verified date: February 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 464
• Est. completion date: February 12, 2029
• Est. primary completion date: February 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Belantamab mafodotin
Belantamab mafodotin will be administered.
• GSK3174998
GSK3174998 will be administered.
• Feladilimab
feladilimab will be administered.
• Nirogacestat
Nirogacestat will be administered.
• Dostarlimab
Dostarlimab will be administered.
• Isatuximab
Isatuximab will be administered.
• Lenalidomide
Lenalidomide will be administered.
• Dexamethasone
Dexamethasone will be administered.
• Pomalidomide
Pomalidomide will be administered.

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Fitzroy	Victoria
Australia	GSK Investigational Site	Melbourne	Victoria
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Salvador	Bahía
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Halifax	Nova Scotia
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Vancouver	British Columbia
France	GSK Investigational Site	Lille Cedex
France	GSK Investigational Site	Lyon cedex 08
France	GSK Investigational Site	Mont-de-Marsan
France	GSK Investigational Site	Villejuif Cedex
Germany	GSK Investigational Site	Frankfurt am Main	Hessen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Kiel	Schleswig-Holstein
Germany	GSK Investigational Site	Leipzig	Sachsen
Greece	GSK Investigational Site	Athens
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Petach Tikva
Israel	GSK Investigational Site	Tel Aviv
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Ulsan
Mexico	GSK Investigational Site	Mexico City
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Dordrecht
Netherlands	GSK Investigational Site	Enschede
Netherlands	GSK Investigational Site	Leeuwarden
Netherlands	GSK Investigational Site	Utrecht
Norway	GSK Investigational Site	Oslo
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Poznan
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	St'Petersburg
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Pamplona
Spain	GSK Investigational Site	Pozuelo (Madrid)
Sweden	GSK Investigational Site	Falun
Sweden	GSK Investigational Site	Stockholm
United States	GSK Investigational Site	Atlanta	Georgia
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Grand Rapids	Michigan
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Madison	Wisconsin
United States	GSK Investigational Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  France,  Germany,  Greece,  Israel,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Norway,  Poland,  Russian Federation,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DE Phase: Number of participants achieving dose limiting toxicities (DLT)	An event is considered to be a DLT if the event occurs within the first 28 days of treatment and meets protocol defined DLT criteria.	Up to 12 months
Primary	DE Phase: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	AEs and SAEs will be collected.	Up to 12 months
Primary	DE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters	Blood and urine samples will be collected to evaluate hematology, clinical chemistry and urinalysis lab parameters.	Up to 12 months
Primary	CE Phase: Number of participants achieving Overall Response Rate (ORR)	ORR is defined as the percentage of participants with a Partial response (PR) or better, according to the International Myeloma Working Group (IMWG) Response Criteria.	Up to 36 months
Secondary	DE Phase: Number of participants achieving ORR	ORR is defined as the percentage of participants with PR or better, according to the IMWG Response Criteria.	Up to 12 months
Secondary	CE Phase: Number of participants achieving Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with a minimal response (MR) or better, according to IMWG response criteria.	Up to 36 months
Secondary	DE Phase: Number of participants achieving Partial Response (PR)	Number of participants with PR according to IMWG criteria will be analyzed.	Up to 12 months
Secondary	CE Phase: Number of participants achieving PR	Number of participants with PR according to IMWG criteria will be analyzed.	Up to 36 months
Secondary	DE Phase: Number of participants achieving Very Good Partial Response (VGPR)	Number of participants with VGPR according to IMWG criteria will be analyzed.	Up to 12 months
Secondary	CE Phase: Number of participants achieving VGPR	Number of participants with VGPR according to IMWG criteria will be analyzed.	Up to 36 months
Secondary	DE Phase: Number of participants achieving Complete Response (CR)	Participants with CR according to IMWG criteria will be analyzed.	Up to 12 months
Secondary	CE Phase: Number of participants achieving CR	Participants with CR according to IMWG criteria will be analyzed.	Up to 36 months
Secondary	DE Phase: Number of participants achieving stringent Complete Response (sCR)	Participants with sCR according to IMWG criteria will be analyzed.	Up to 12 months
Secondary	CE Phase: Number of participants achieving sCR	Participants with sCR according to IMWG criteria will be analyzed.	Up to 36 months
Secondary	DE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments	Blood samples will be collected for concentrations of belantamab mafodotin.	Up to 12 months
Secondary	CE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments	Blood samples will be collected for concentrations of belantamab mafodotin.	Up to 36 months
Secondary	DE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin	Blood samples will be collected for concentrations of GSK3174998.	Up to 12 months
Secondary	CE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin	Blood samples will be collected for concentrations of GSK3174998.	Up to 36 months
Secondary	DE Phase: Feladilimab concentration when administered in combination with belantamab mafodotin	Blood samples will be collected for concentrations of feladilimab.	Up to 12 months
Secondary	CE Phase: Feladilimab concentration when administered in combination with belantamab mafodotin	Blood samples will be collected for concentrations of feladilimab.	Up to 36 months
Secondary	DE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin	Blood samples will be collected for concentrations of nirogacestat.	Up to 12 months
Secondary	CE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin	Blood samples will be collected for concentrations of nirogacestat.	Up to 36 months
Secondary	DE Phase: Dostarlimab concentration when administered in combination with belantamab mafodotin	Blood samples will be collected for concentrations of dostarlimab.	Up to 12 months
Secondary	CE Phase: Dostarlimab concentration when administered in combination with belantamab mafodotin	Blood samples will be collected for concentrations of dostarlimab.	Up to 36 months
Secondary	DE Phase: Isatuximab concentration when administered in combination with belantamab mafodotin	Blood samples will be collected for concentrations of isatuximab.	Up to 12 months
Secondary	CE Phase: Isatuximab concentration when administered in combination with belantamab mafodotin	Blood samples will be collected for concentrations of isatuximab.	Up to 36 months
Secondary	DE Phase: Concentration of anti-drug antibodies (ADAs) against belantamab mafodotin when administered in combination with anti-cancer treatments	Blood samples for concentrations for ADAs will be collected.	Up to 12 months
Secondary	CE Phase: Concentration of ADAs against belantamab mafodotin when administered in combination with anti-cancer treatments	Blood samples for concentrations for ADAs will be collected.	Up to 36 months
Secondary	DE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin	Blood samples for concentrations for ADAs will be collected.	Up to 12 months
Secondary	CE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin	Blood samples for concentrations for ADAs will be collected.	Up to 36 months
Secondary	DE Phase: Concentration of ADAs against feladilimab when administered in combination with belantamab mafodotin	Blood samples for concentrations for ADAs will be collected.	Up to 12 months
Secondary	CE Phase: Concentration of ADAs against feladilimab when administered in combination with belantamab mafodotin	Blood samples for concentrations for ADAs will be collected.	Up to 36 months
Secondary	DE Phase: Concentration of ADAs against dostarlimab when administered in combination with belantamab mafodotin	Blood samples for concentrations for ADAs will be collected.	Up to 12 months
Secondary	CE Phase: Concentration of ADAs against dostarlimab when administered in combination with belantamab mafodotin	Blood samples for concentrations for ADAs will be collected.	Up to 36 months
Secondary	DE Phase: Concentration of ADAs against isatuximab when administered in combination with belantamab mafodotin	Blood samples for concentrations for ADAs will be collected.	Up to 12 months
Secondary	CE Phase: Concentration of ADAs against isatuximab when administered in combination with belantamab mafodotin	Blood samples for concentrations for ADAs will be collected.	Up to 36 months
Secondary	DE Phase: Number of participants with adverse events of special interest (AESI) for belantamab mafodotin	AESIs will be collected.	Up to 12 months
Secondary	CE Phase: Number of participants with AESI for belantamab mafodotin	AESIs will be collected.	Up to 36 months
Secondary	DE Phase: Number of participants with AESI for GSK3174998	AESIs will be collected.	Up to 12 months
Secondary	CE Phase: Number of participants with AESI for GSK3174998	AESIs will be collected.	Up to 36 months
Secondary	DE Phase: Number of participants with AESI for Feladilimab	AESIs will be collected.	Up to 12 months
Secondary	CE Phase: Number of participants with AESI for Feladilimab	AESIs will be collected.	Up to 36 months
Secondary	DE Phase: Number of participants with AESI for Nirogacestat	AESIs will be collected.	Up to 12 months
Secondary	CE Phase: Number of participants with AESI for Nirogacestat	AESIs will be collected.	Up to 36 months
Secondary	DE Phase: Number of participants with AESI for Dostarlimab	AESIs will be collected.	Up to 12 months
Secondary	CE Phase: Number of participants with AESI for Dostarlimab	AESIs will be collected.	Up to 36 months
Secondary	DE Phase: Number of participants with AESI for Isatuximab	AESIs will be collected.	Up to 12 months
Secondary	CE Phase: Number of participants with AESI for Isatuximab	AESIs will be collected.	Up to 36 months
Secondary	DE Phase: Number of participants with abnormal ocular findings on ophthalmic examination	Ophthalmic examination will assess abnormal findings.	Up to 12 months
Secondary	CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination	Ophthalmic examination will assess abnormal findings.	Up to 36 months
Secondary	CE Phase: Number of participants achieving Progression-free survival (PFS)	PFS is defined as the time from randomization until the earliest date of confirmed progressive disease (PD) per IMWG, or death due to any cause.	Up to 36 months
Secondary	CE Phase: Duration of response (DoR)	DoR is defined as the time from first documented evidence or PR or better until progressive disease per IMWG or death due to progressive disease among participants who achieve confirmed partial response or better.	Up to 36 months
Secondary	CE Phase: Time to response (TTR)	TTR is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (confirmed PR or better).	Up to 36 months
Secondary	CE Phase: Number of participants achieving Overall survival (OS)	OS is defined as the time from randomization until death due to any cause.	Up to 36 months
Secondary	CE Phase: Number of participants with AEs and SAEs	AEs and SAEs will be collected.	Up to 36 months
Secondary	CE Phase: Number of participants with AEs leading to discontinuation	Number of participants with AEs leading to discontinuation will be evaluated.	Up to 36 months
Secondary	CE Phase: Number of participants with dose reduction or delay	Number of participants with dose reduction or delay will be evaluated.	Up to 36 months
Secondary	CE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters	Blood and urine samples will be collected to evaluate hematology, clinical chemistry and urinalysis lab parameters.	Up to 36 months