A Study to Investigate the Safety and Efficacy of Belantamab for the Treatment of Multiple Myeloma When Used as Monotherapy and in Combination Treatments (DREAMM-20)

• ClinicalTrials.gov Identifier: NCT05714839
• Recruitment Status: Not yet recruiting
• First Posted: February 6, 2023
• Last Update Posted: February 6, 2023
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

The study consists of three parts

• Part 1: The primary purpose of this part is to determine the safety, and recommended part 2 dose of belantamab (bela) in participants with relapsed or refractory multiple myeloma (RRMM).
• Part 2: The primary purpose of this part is to determine safety, tolerability and percentage of adverse events (AEs) that happen to eyes in participants with RRMM treated with bela in combination with other treatments.
• Part 3: The primary objective of this part is to assess the safety, tolerability and rate of ocular AEs in participants with transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM) treated with either belantamab mafodotin (belamaf) or bela in combination with other treatments.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Bela; Drug: Belamaf; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Standard of Care	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 124 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Open-label, Multicentre, Dose Escalation and Expansion Study to Investigate the Safety, Tolerability, and Clinical Activity of Belantamab as Monotherapy and in Combination With Other Treatments in Participants With Multiple Myeloma
• Estimated Study Start Date: February 28, 2023
• Estimated Primary Completion Date: June 28, 2027
• Estimated Study Completion Date: June 28, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1 - Dose Escalation Phase in Participants with RRMM; Bela will be administered in participants with RRMM until progressive disease (PD). Participants may switch to Belamaf in case of PD.	Drug: Bela; Bela will be administered.; Other Names: Belantamab; GSK2857914; Drug: Belamaf; Belamaf will be administered.; Other Names: Belantamab mafodotin; GSK2857916 BLENREP
Experimental: Part 2 - Combination Treatments in Participants with RRMM; Participants with RRMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma.	Drug: Bela; Bela will be administered.; Other Names: Belantamab; GSK2857914; Drug: Belamaf; Belamaf will be administered.; Other Names: Belantamab mafodotin; GSK2857916 BLENREP; Drug: Lenalidomide; Lenalidomide will be administered.; Drug: Dexamethasone; Dexamethasone will be administered.; Drug: Standard of Care; Either standard of care (SoC) or an emerging treatment for Multiple Myeloma will be administered
Experimental: Part 3 - Combination Treatments in Participants with TI-NDMM; Participants with TI-NDMM will receive Bela-xRd and Belamaf-xRd. The combination treatment xRd includes lenalidomide (R) and dexamethasone (d). x will be either a standard of care (SoC) or an emerging treatment for Multiple Myeloma.	Drug: Bela; Bela will be administered.; Other Names: Belantamab; GSK2857914; Drug: Belamaf; Belamaf will be administered.; Other Names: Belantamab mafodotin; GSK2857916 BLENREP; Drug: Lenalidomide; Lenalidomide will be administered.; Drug: Dexamethasone; Dexamethasone will be administered.; Drug: Standard of Care; Either standard of care (SoC) or an emerging treatment for Multiple Myeloma will be administered

Outcome Measures

Primary Outcome Measures :

1. Part 1, 2 and 3: Number of Participants with any Adverse Event [ Time Frame: Up to 52 months ]
2. Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (Each cycle is of 28 days) ]
3. Part 1, 2 and 3: Number of Participants with Worst Case Grade Change from Baseline in Laboratory and Vital Sign Parameters [ Time Frame: Up to 52 months ]
4. Part 2 and 3: Number of Participants with Corneal Adverse Events (CAEs) [ Time Frame: Up to 52 months ]

Secondary Outcome Measures :

1. Part 1, 2 and 3: Observed Plasma Concentration of Bela [ Time Frame: Up to 52 months ]
2. Part 1, 2 and 3: Area Under the Curve (AUC) of Bela [ Time Frame: Up to 52 months ]
3. Part 1, 2 and 3: Maximum Concentration (Cmax) of Bela [ Time Frame: Up to 52 months ]
4. Part 1, 2 and 3: Number of Participants with Anti-Drug Antibodies (ADA) against Bela [ Time Frame: Up to 52 months ]
5. Part 1, 2 and 3: Titers of ADA against Bela [ Time Frame: Up to 52 months ]
6. Part 2 and 3: Number of Participants with ADAs against Belamaf [ Time Frame: Up to 52 months ]
7. Part 2 and 3: Titers of ADAs against Belamaf [ Time Frame: Up to 52 months ]
8. Part 1, 2 and 3: Objective Response Rate (ORR) [ Time Frame: Up to 52 months ]
   ORR is defined as the percentage of participants with a confirmed Partial Response (PR) or better [i.e., PR, Very Good Partial Response (VGPR), Complete Response (CR), Stringent Complete Response (sCR)] as per International Myeloma Working Group (IMWG) criteria.
9. Part 2 and 3: Stringent Complete Response (sCR) Rate [ Time Frame: Up to 52 months ]
   sCR is defined as the percentage of participants with CR plus normal free light chain ratio and absence of clonal cells in the bone marrow (BM) as per IMWG criteria.
10. Part 2 and 3: Complete Response (CR) Rate [ Time Frame: Up to 52 months ]
    CR rate is defined as the percentage of participants with a confirmed CR or better (i.e., CR, sCR) as per IMWG criteria.
11. Part 2 and 3: Very Good Partial Response (VGPR) Rate [ Time Frame: Up to 52 months ]
    VGPR rate is defined as the percentage of participants with a confirmed VGPR or better (i.e., VGPR, CR, sCR) as per IMWG criteria.
12. Part 2 and 3: Observed Plasma Concentration of Belamaf [ Time Frame: Up to 52 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Participants at the time of signing the Informed Consent Form (ICF) are at least 18 years old or are of the legal age of consent in the jurisdiction in which the study is taking place.
• Participants who have histologically or cytologically confirmed diagnosis of Multiple Myeloma (MM), as defined by the IMWG, and measurable disease.
• PART 1: Participants who have received at least 3 prior lines of anti-myeloma treatments, and have already received an immunomodulating agent, a proteasome inhibitor, and an anti-CD38 mAb (unless contraindicated or unavailable). Lines of therapy are defined by consensus panel of the International Myeloma Workshop.
• PART 2: Participants who meet all of the following:
• Have undergone Autologous stem cell transplant (ASCT) or are considered transplant ineligible
• Have been previously treated with at least ONE prior line of MM therapy
• Have documented disease progression during or after their most recent therapy
• PART 3: Participants who meet both of the following:
• NDMM with a requirement for treatment as documented per IMWG criteria

• Not considered a candidate for high dose chemotherapy with ASCT due to:

  1. Age ≥ 65 years OR
  2. Age 18-65 years with presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT or who refuse high-dose chemotherapy with ASCT as an initial treatment.
• Participants capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and protocol.

Exclusion Criteria:

• Diagnosis of primary Amyloid Light chain (AL) Amyloidosis, active Polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes (POEMS) syndrome, primary plasma cell leukemia.
• Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with participant's safety, obtaining informed consent, or compliance with study procedures.
• Active infection requiring antibiotic, antiviral, or antifungal treatment.
• Known, current drug or alcohol abuse.
• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this trial, unless prospective Independent Review Board (IRB) approval (by chair or designee) is allowing exception to this criterion for a specific participant.

Contacts and Locations

Contacts

Contact: US GSK Clinical Trials Call Center; 877-379-3718; GSKClinicalSupportHD@gsk.com

Contact: EU GSK Clinical Trials Call Center; +44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT05714839
• Other Study ID Numbers: 218670; 2022-501941-63 ( EudraCT Number )
• First Posted: February 6, 2023
• Last Update Posted: February 6, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• URL: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

Bela; Belamaf; Belatamab; Belantamab Mafodotin; Relapsed or Refractory Multiple Myeloma; Transplant-ineligible newly diagnosed multiple myeloma

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Dexamethasone; Lenalidomide; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents