Platform Study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination with Anti-Cancer Treatments in Participants with RRMM.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Jan 2020 → ongoing

Decision date (initial)

2024-08-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509550-55-00

EudraCT number

2019-001138-32

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Dose Exploration:
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 sub-study investigational combination treatment to explore in the CE Phase in participants with RRMM

Cohort Expansion:
To assess the clinical activity of belantamab mafodotin at each potential RP2D in combination with anti-cancer treatments compared to belantamab mafodotin monotherapy within each sub-study in participants with RRMM

Secondary objectives 10

1. Dose Exploration - Key Secondary To evaluate the clinical measures of efficacy of belantamab mafodotin and combination treatments in participants with RRMM
2. Dose Exploration: To further evaluate the clinical measures of efficacy of belantamab mafodotin and combination treatments in each sub-study in participants with RRMM
3. Dose Exploration: To describe the exposure of belantamab mafodotin when administered in combination with each combination treatment within each sub-study in participants with RRMM
4. Dose Exploration: To describe the exposure of the partner anti-cancer treatment when administered in combination with belantamab mafodotin in each sub-study
5. Dose Exploration To assess ADAs against belantamab mafodotin and against combination treatments (biologics) that are administered by IV infusion within each sub-study
6. Dose Exploration: To further determine the safety and tolerability of belantamab mafodotin in combination with other anti-cancer treatments (in each sub-study)
7. Cohort Expansion Secondary end points To further assess clinical activity of combination treatments with belantamab mafodotin at each potential RP2D compared with monotherapy within each sub-study in participants with RRMM
8. Cohort Expansion: To further characterize the safety of belantamab mafodotin in combination with anti-cancer treatments within each sub-study in participants with RRMM
9. Cohort Expansion: To evaluate plasma concentrations of belantamab mafodotin and combination treatments in participants within each sub-study with RRMM
10. Cohort Expansion: To assess ADAs against belantamab mafodotin and against combination treatments (biologics) that are administered by IV infusion within each sub-study

Conditions and MedDRA coding

Multiple Myeloma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Principal Inclusion Criteria Master Protocol: 1. 18 years of age inclusive or older, at the time of signing the informed consent.
2. 2. Histologically or cytologically confirmed diagnosis of MM, as defined by the International Myeloma Working Group
3. 3. Treated with at least 3 prior lines of anti-myeloma treatments including an immunomodulating agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody.
4. 4. History of autologous stem cell transplant are eligible for study participation provided the following eligibility criteria are met: a. transplant was >100 days prior to Screening. b. no active infection(s).
5. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, unless ECOG ≤2 is due solely to skeletal complications and/or skeletal pain due to MM.
6. 6. Measurable disease
7. 7. Have organ system functions as defined by the laboratory assessments in Table 15
8. 8. Positive for HBcAb can be enrolled if criteria are met
9. 9. All prior treatment-related toxicities (defined by National Cancer Institute-Common Toxicity Criteria for Adverse Events [NCI-CTCAE], Version 5.0, 2017) must be Grade </=1 at the time of Screening except for alopecia (any Grade), neuropathy (Grade </=2), or endocrinopathy managed with replacement therapy (any Grade).
10. 10. Physiological doses oral steroids (<10 mg/day), inhaled steroids or ophthalmological steroids are allowed on study.
11. 11. Male or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception
12. 12. Participants or legally authorized representative (LAR) sign written informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Note: Use of LAR is not applicable for Germany.
13. SS3: For Inclusion Criterion 11: please note contraception requirements specific to Sub study 3 (Section 8.3.7.2).
14. SS6: For MP Inclusion Criterion 11: please note contraception requirements specific to Sub study 6 (Section 8.3.7.2).
15. SS6: For MP Inclusion Criteria 7 (MP Table 15): For Sub-study 6 the Platelets value for Adequate Organ System Function is >/=75 × 109/L.
16. SS7: For MP Inclusion Criterion 11: please note contraception requirements specific to Sub study 7 (Section 8.2.8.2).
17. SS7: For MP Inclusion Criteria 7 (MP Table 15): For Sub-study 7 the platelets value for adequate organ system function is >/=75 × 109/L.

Exclusion criteria 58

1. Exclusion Criteria Master: 1. Symptomatic amyloidosis, active ‘polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes’ (POEMS) syndrome, current or past diagnosis of plasma cell leukemia, as per 2021 IMWG guidelines (Fernández de Larrea et al 2021).
2. 25. Known, current drug or alcohol abuse.
3. 26. 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 study, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific participant.
4. 18. Prior allogeneic transplant is prohibited.
5. Exclusion Criteria SS2: The exclusion criteria #27 and #28 below are in addition to the exclusion criteria already defined in 208887 MP Section 5.2. Please note: The numbering in the criteria may not be sequential from the MP.
6. SS2: 28. In addition, exclusion for a recent (within the past 6 months) history of symptomatic pericarditis.
7. Exclusion Criteria SS3: The exclusion criteria #29, #30, #31, #32, #33, and #60 below are in addition to the exclusion criteria already defined in 208887 MP Section 5.2. Please note: The numbering in the criteria may not be sequential from the MP. Note: for Germany, female participants of childbearing potential using hormonal contraception at the time of inclusion/exclusion criteria screening are excluded. Participants are excluded from the study if any of the following criteria apply: SS3: 29. Uncontrolled small and/or large intestinal disease.
8. 8. Active infection requiring antibiotic, antiviral, or antifungal treatment.
9. SS3: 30. Uncontrolled skin disease.
10. 12. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at Screening or within 3 months prior to first dose of study treatment.
11. 13. Presence of active renal condition
12. 4. Current unstable liver or biliary disease per investigator assessment
13. 14. Participants who have received prior therapy with belantamab mafodotin are excluded. Participants previously treated with other BCMA-targeting agents, such as CAR-T cells or bispecific antibodies, are permitted only during the DE Phase.
14. 15. Other monoclonal antibodies within 30 days or systemic anti-myeloma therapy within <14 days of first dose of study drug.
15. 16. Prior radiotherapy within 2 weeks of start of study therapy.
16. 19. Participants who have received prior CAR-T therapy with lymphodepletion with chemotherapy within 3 months of Screening.
17. 17. Plasmapheresis within 7 days prior to the first dose of study drug.
18. SS3: 31. Any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement.
19. SS3: 32. Previous administration of a gamma-secretase inhibitor.
20. SS3: 33. Concomitant administration of a strong or moderate CYP3A4 inhibitor or inducer (see Section 6.5.2).
21. SS3: 60. Known HIV infection, unless the participant can meet all criteria listed in exclusion criterion 9 in the MP Section 5.2, in which case the participant would be eligible for CE Phase only. Note: for patients receiving nirogacestat, HIV drugs that are strong 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 outlined in Section 6.5.2.
22. Exclusion Criteria SS5: The exclusion criteria #39-41 below are in addition to the Exclusion Criteria already defined in 208887 MP Section 5.2. Please note: The numbering in the criteria may not be sequential from the MP.
23. 5. Malignancies other than disease under study are excluded
24. SS5: 39. Severe hypersensitivity to Isatuximab-irfc or to any of its excipients.
25. SS5: 40. Prior treatment with other anti-CD38 monoclonal antibody within 6 months of the first dose of study drug treatment.
26. SS5: 41. Known intolerance or hypersensitivity to infused proteins products, sucrose, histidine, and polysorbate 80.
27. Exclusion Criteria SS6: The exclusion criteria #42 to #50, and #60 below are in addition to the exclusion criteria already defined in 208887 MP Section 5.2. The numbering in the criteria may not be sequential from the MP. Note: for Germany, female participants of childbearing potential using hormonal contraception at the time of inclusion/exclusion criteria screening are excluded. Participants are excluded from the study if any of the following criteria apply: SS6 42. Uncontrolled small and/or large intestinal disease
28. 9. Known HIV infection unless criteria are met
29. SS6: 43. Uncontrolled skin disease
30. 20. Any major surgery (other than bone-stabilizing surgery) within 30 days of first dose.
31. 11. Presence of hepatitis B surface antigen (HBsAg) at Screening or within prior history.
32. 10. Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
33. 2. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with participants safety, obtaining informed consent, or compliance with study procedures.
34. 7. 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 mAbs.
35. 3. Current corneal epithelial disease except mild punctate keratopathy.
36. SS6: 44. Any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement
37. SS6: 45. Previous administration of a gamma-secretase inhibitor
38. SS6: 46. Concomitant administration of a strong CYP3A4 inhibitor or inducer (see Section 6.5.2.1).
39. SS6: 47. Active or history of venous thromboembolism within the past 3 months.
40. SS6: 48. Evidence of active mucosal or internal bleeding.
41. SS6: 49. Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis or unable to tolerate antithrombolytic prophylaxis
42. SS6: 50. Discontinuation of prior treatment with lenalidomide due to intolerable AEs.
43. SS6: 60. Known HIV infection, unless the participant can meet all criteria listed in exclusion criterion 9 in the MP Section 5.2, in which case the participant would be eligible for CE Phase only. Note: for patients receiving nirogacestat, HIV drugs that are strong 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 outlined in Section 6.5.2.
44. Exclusion Criteria SS7: The exclusion criteria #51 to #60 below are in addition to the exclusion criteria already defined in 208887 MP Section 5.2. Please note: The numbering in the criteria may not be sequential from the MP. Note: for Germany, female participants of childbearing potential using hormonal contraception at the time of inclusion/exclusion criteria screening are excluded. Participants are excluded from the study if any of the following criteria apply: SS7: 51. Uncontrolled small and/or large intestinal disease.
45. 6. Evidence of cardiovascular risk
46. SS7: 52. Uncontrolled skin disease.
47. 21. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose of study drugs, or treatment with an investigational agent or approved systemic anti-myeloma therapy (including systemic steroids) within 14 days or 5 half-lives of receiving the first dose of study drugs, whichever is shorter.
48. Other Exclusions 22. Pregnant or lactating female.
49. 23. Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony stimulating factor [GM CSF], recombinant erythropoietin) or any thrombopoietin receptor agonists within 2 weeks before the first dose of study drug.
50. 24. Participants must not receive live/live attenuated vaccines within 30 days prior to first dose of study treatment or whilst receiving belantamab mafodotin +/-partner agent
51. SS7: 53. Any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement.
52. SS7: 54. Previous administration of a gamma-secretase inhibitor.
53. SS7: 55. Concomitant administration of a strong CYP3A4 inhibitor or inducer (see Section 6.5.2.1).
54. SS7: 56. Active or history of venous thromboembolism within the past 3 months.
55. SS7: 57. Evidence of active mucosal or internal bleeding.
56. SS7: 58. Contraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis or unable to tolerate antithrombotic prophylaxis.
57. SS7: 59. Discontinuation of prior treatment with pomalidomide due to intolerable adverse events.
58. SS7: 60. Known HIV infection, unless the participant can meet all criteria listed in exclusion criterion 9 in the MP Section 5.2, in which case the participant would be eligible for CE Phase only. Note: for patients receiving nirogacestat, HIV drugs that are strong 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 outlined in Section 6.5.2.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Dose Exploration: • Percentage (number) of participants with DLTs
2. Dose Exploration: • Percentage of participants with AEs, changes in clinical signs and laboratory parameters
3. Cohort Expansion: • ORR, according to the IMWG Response Criteria [Kumar, 2016]

Secondary endpoints 19

1. Key Secondary end point Dose Exploration: • Clinical activity measured as ORR, according to IMWG Response Criteria
2. Secondary End points Dose Exploration: Rates of PR, VGPR, CR, sCR
3. Belantamab mafodotin observed concentrations
4. Anticancer combination observed concentrations
5. Incidence and titers of ADAs against belantamab mafodotin & combination treatments
6. Incidence of AEs of special interest for belantamab mafodotin and combination treatments
7. Incidence of ocular findings on ophthalmic exam
8. Secondary end points Cohort Expansion: CBR according to the IMWG Response Criteria [Kumar, 2016]
9. PFS
10. DoR
11. TTR
12. Rates of: PR, VGPR; CR, sCR
13. OS
14. Incidence of AEs, SAEs, AEs leading to discontinuation or dose reduction/delay, changes in clinical signs, and laboratory parameters.
15. Incidence of AESIs for belantamab mafodotin.
16. Incidence of AESIs for the individual partner for each sub-study.
17. Incidence of ocular findings on ophthalmic exam for belantamab mafodotin.
18. Belantamab mafodotin and combination treatment’s plasma concentrations
19. Incidence and titers of ADAs against belantamab mafodotin and combination treatments, when measured

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 23

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 21

Locations

4 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 113 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications