Platform Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With aOX40 (GSK3174998) in Participants With RRMM

Study Overview
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Brief Summary
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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 the sub study of the Master protocol (NCT04126200).

Official Title
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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 1 - Belantamab Mafodotin and aOX40 (GSK3174998) in Combination

Conditions
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Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: Belantamab Mafodotin
* Drug: GSK3174998


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Belantamab mafodotin + GSK3174998<br> | Drug: Belantamab Mafodotin<br>* Belantamab Mafodotin will be administered.<br>* Other names: GSK2857916;Drug: GSK3174998<br>* GSK3174998 will be administered.<br>* Other names: aOX40;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DE Phase: Number of participants with dose limiting toxicities (DLT) |  | Up to 170 weeks | 
| DE Phase: Number of participants with adverse events (AEs) and serious adverse events (SAEs) |  | Up to 170 weeks | 
| DE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters |  | Up to 170 weeks | 
| CE Phase: 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 170 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DE Phase: Overall Response Rate | ORR is defined as the percentage of participants with PR or better, according to the IMWG Response Criteria. | Up to 170 weeks | 
| CE Phase: 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 170 weeks | 
| DE Phase: Number of participants achieving Partial Response (PR) | Number of participants with PR according to IMWG criteria will be analyzed. | Up to 170 weeks | 
| CE Phase: Number of participants achieving PR | Number of participants with PR according to IMWG criteria will be analyzed. | Up to 170 weeks | 
| 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 170 weeks | 
| CE Phase: Number of participants achieving VGPR | Number of participants with VGPR according to IMWG criteria will be analyzed. | Up to 170 weeks | 
| DE Phase: Number of participants achieving Complete Response (CR) | Participants with CR according to IMWG criteria will be analyzed. | Up to 170 weeks | 
| CE Phase: Number of participants achieving CR | Participants with CR according to IMWG criteria will be analyzed. | Up to 170 weeks | 
| DE Phase: Number of participants achieving stringent Complete Response (sCR) | Participants with sCR according to IMWG criteria will be analyzed. | Up to 170 weeks | 
| CE Phase: Number of participants achieving sCR | Participants with sCR according to IMWG criteria will be analyzed. | Up to 170 weeks | 
| DE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments |  | Up to 170 weeks | 
| CE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments |  | Up to 170 weeks | 
| DE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin |  | Up to 170 weeks | 
| CE Phase: GSK3174998 concentration when administered in combination with belantamab mafodotin |  | Up to 170 weeks | 
| DE Phase: Concentration of anti-drug antibodies (ADAs) against belantamab mafodotin when administered in combination with anti-cancer treatments |  | Up to 170 weeks | 
| CE Phase: Concentration of ADAs against belantamab mafodotin when administered in combination with anti-cancer treatments |  | Up to 170 weeks | 
| DE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin |  | Up to 170 weeks | 
| CE Phase: Concentration of ADAs against GSK3174998 when administered in combination with belantamab mafodotin |  | Up to 170 weeks | 
| DE Phase: Number of participants with adverse events of special interest (AESI) for belantamab mafodotin |  | Up to 170 weeks | 
| CE Phase: Number of participants with AESI for belantamab mafodotin |  | Up to 170 weeks | 
| DE Phase: Number of participants with AESI for GSK3174998 |  | Up to 170 weeks | 
| CE Phase: Number of participants with AESI for GSK3174998 |  | Up to 170 weeks | 
| DE Phase: Number of participants with abnormal ocular findings on ophthalmic examination |  | Up to 170 weeks | 
| CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination |  | Up to 170 weeks | 
| CE Phase: 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 170 weeks | 
| 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 170 weeks | 
| 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 170 weeks | 
| CE Phase: Overall survival (OS) | OS is defined as the time from randomization until death due to any cause. | Up to 170 weeks | 
| CE Phase: Number of participants with AEs and SAEs |  | Up to 170 weeks | 
| CE Phase: Number of participants with AEs leading to discontinuation |  | Up to 170 weeks | 
| CE Phase: Number of participants with AEs with dose reduction or delay |  | Up to 170 weeks | 
| CE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters |  | Up to 170 weeks |