BELANTAMAB MAFODOTIN for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- Principal Inclusion Criteria Master Protocol: 1. 18 years of age inclusive or older, at the time of signing the informed consent."}
• {"criterion_text":"- 10.\tPhysiological doses oral steroids (<10 mg/day), inhaled steroids or ophthalmological steroids are allowed on study."}
• {"criterion_text":"- 11.\tMale or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- SS3: For Inclusion Criterion 11: please note contraception requirements specific to Sub study 3 (Section 8.3.7.2)."}
• {"criterion_text":"- SS6: For MP Inclusion Criterion 11: please note contraception requirements specific to Sub study 6 (Section 8.3.7.2)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- SS7: For MP Inclusion Criterion 11: please note contraception requirements specific to Sub study 7 (Section 8.2.8.2)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 2. Histologically or cytologically confirmed diagnosis of MM, as defined by the International Myeloma Working Group"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 4.\tHistory 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)."}
• {"criterion_text":"- 5.\tEastern 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."}
• {"criterion_text":"- 6.\tMeasurable disease"}
• {"criterion_text":"- 7.\tHave organ system functions as defined by the laboratory assessments in Table 15"}
• {"criterion_text":"- 8.\tPositive for HBcAb can be enrolled if criteria are met"}
• {"criterion_text":"- 9.\tAll 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)."}

Exclusion criteria

• {"criterion_text":"- Exclusion Criteria Master: 1.\tSymptomatic 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)."}
• {"criterion_text":"- 12.\tPositive 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."}
• {"criterion_text":"- 13.\tPresence of active renal condition"}
• {"criterion_text":"- 4.\tCurrent unstable liver or biliary disease per investigator assessment"}
• {"criterion_text":"- 14.\tParticipants 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."}
• {"criterion_text":"- 15.\tOther monoclonal antibodies within 30 days or systemic anti-myeloma therapy within <14 days of first dose of study drug."}
• {"criterion_text":"- 16.\tPrior radiotherapy within 2 weeks of start of study therapy."}
• {"criterion_text":"- 19.\tParticipants who have received prior CAR-T therapy with lymphodepletion with chemotherapy within 3 months of Screening."}
• {"criterion_text":"- 17.\tPlasmapheresis within 7 days prior to the first dose of study drug."}
• {"criterion_text":"- SS3: 31.\tAny condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement."}
• {"criterion_text":"- SS3: 32.\tPrevious administration of a gamma-secretase inhibitor."}
• {"criterion_text":"- 25.\tKnown, current drug or alcohol abuse."}
• {"criterion_text":"- SS3: 33.\tConcomitant administration of a strong or moderate CYP3A4 inhibitor or inducer (see Section 6.5.2)."}
• {"criterion_text":"- SS3: 60.\tKnown 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 5.\tMalignancies other than disease under study are excluded"}
• {"criterion_text":"- SS5: 39.\tSevere hypersensitivity to Isatuximab-irfc or to any of its excipients."}
• {"criterion_text":"- SS5: 40.\tPrior treatment with other anti-CD38 monoclonal antibody within 6 months of the first dose of study drug treatment."}
• {"criterion_text":"- SS5: 41.\tKnown intolerance or hypersensitivity to infused proteins products, sucrose, histidine, and polysorbate 80."}
• {"criterion_text":"- 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.\tUncontrolled small and/or large intestinal disease"}
• {"criterion_text":"- 9.\tKnown HIV infection unless criteria are met"}
• {"criterion_text":"- SS6: 43.\tUncontrolled skin disease"}
• {"criterion_text":"- 26.\tIs 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."}
• {"criterion_text":"- 20.\tAny major surgery (other than bone-stabilizing surgery) within 30 days of first dose."}
• {"criterion_text":"- 11.\tPresence of hepatitis B surface antigen (HBsAg) at Screening or within prior history."}
• {"criterion_text":"- 10.\tRecent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction."}
• {"criterion_text":"- 2.\tAny 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."}
• {"criterion_text":"- 7.\tKnown 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."}
• {"criterion_text":"- 3.\tCurrent corneal epithelial disease except mild punctate keratopathy."}
• {"criterion_text":"- SS6: 44.\tAny condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement"}
• {"criterion_text":"- SS6: 45.\tPrevious administration of a gamma-secretase inhibitor"}
• {"criterion_text":"- SS6: 46.\tConcomitant administration of a strong CYP3A4 inhibitor or inducer (see Section 6.5.2.1)."}
• {"criterion_text":"- SS6: 47.\tActive or history of venous thromboembolism within the past 3 months."}
• {"criterion_text":"- SS6: 48.\tEvidence of active mucosal or internal bleeding."}
• {"criterion_text":"- SS6: 49.\tContraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis or unable to tolerate antithrombolytic prophylaxis"}
• {"criterion_text":"- SS6: 50.\tDiscontinuation of prior treatment with lenalidomide due to intolerable AEs."}
• {"criterion_text":"- SS6: 60.\tKnown 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."}
• {"criterion_text":"- 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.\tUncontrolled small and/or large intestinal disease."}
• {"criterion_text":"- 6.\tEvidence of cardiovascular risk"}
• {"criterion_text":"- SS7: 52.\tUncontrolled skin disease."}
• {"criterion_text":"- 21.\tPrior 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."}
• {"criterion_text":"- Other Exclusions 22.\tPregnant or lactating female."}
• {"criterion_text":"- 23.\tHas 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 24.\tParticipants must not receive live/live attenuated vaccines within 30 days prior to first dose of study treatment or whilst receiving belantamab mafodotin +/-partner agent"}
• {"criterion_text":"- SS7: 53.\tAny condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement."}
• {"criterion_text":"- SS7: 54.\tPrevious administration of a gamma-secretase inhibitor."}
• {"criterion_text":"- SS7: 55.\tConcomitant administration of a strong CYP3A4 inhibitor or inducer (see Section 6.5.2.1)."}
• {"criterion_text":"- SS7: 56.\tActive or history of venous thromboembolism within the past 3 months."}
• {"criterion_text":"- SS7: 57.\tEvidence of active mucosal or internal bleeding."}
• {"criterion_text":"- SS7: 58.\tContraindications to or unwilling to undergo protocol-required anti-thrombotic prophylaxis or unable to tolerate antithrombotic prophylaxis."}
• {"criterion_text":"- SS7: 59.\tDiscontinuation of prior treatment with pomalidomide due to intolerable adverse events."}
• {"criterion_text":"- SS7: 60.\tKnown 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."}
• {"criterion_text":"- SS2: 28.\tIn addition, exclusion for a recent (within the past 6 months) history of symptomatic pericarditis."}
• {"criterion_text":"- 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.\tUncontrolled small and/or large intestinal disease."}
• {"criterion_text":"- 8.\tActive infection requiring antibiotic, antiviral, or antifungal treatment."}
• {"criterion_text":"- SS3: 30.\tUncontrolled skin disease."}

Primary endpoints

• {"endpoint_text":"- Dose Exploration: •\tPercentage (number) of participants with DLTs","definition_or_measurement_approach":"Percentage (number) of participants with DLTs (Dose Limiting Toxicities) as measured during Dose Exploration"}
• {"endpoint_text":"- Dose Exploration: •\tPercentage of participants with AEs, changes in clinical signs and laboratory parameters","definition_or_measurement_approach":"Percentage of participants with AEs and changes in clinical signs and laboratory parameters as assessed during Dose Exploration"}
• {"endpoint_text":"- Cohort Expansion: •\tORR, according to the IMWG Response Criteria [Kumar, 2016]","definition_or_measurement_approach":"Overall response rate (ORR) assessed according to the IMWG Response Criteria [Kumar, 2016]"}

Secondary endpoints

• {"endpoint_text":"- Key Secondary end point Dose Exploration: •\tClinical activity measured as ORR, according to IMWG Response Criteria","definition_or_measurement_approach":"Clinical activity measured as ORR per IMWG Response Criteria"}
• {"endpoint_text":"- Secondary End points Dose Exploration: Rates of PR, VGPR, CR, sCR","definition_or_measurement_approach":"Rates of PR, VGPR, CR, sCR (per IMWG criteria)"}
• {"endpoint_text":"- Belantamab mafodotin observed concentrations","definition_or_measurement_approach":"Observed plasma concentrations of belantamab mafodotin"}
• {"endpoint_text":"- Anticancer combination observed concentrations","definition_or_measurement_approach":"Observed plasma concentrations of the anticancer combination partner(s)"}
• {"endpoint_text":"- Incidence and titers of ADAs against belantamab mafodotin & combination treatments","definition_or_measurement_approach":"Incidence and titers of anti-drug antibodies (ADAs) measured against belantamab mafodotin and combination treatments"}
• {"endpoint_text":"- Incidence of AEs of special interest for belantamab mafodotin and combination treatments","definition_or_measurement_approach":"Incidence of predefined adverse events of special interest (AESIs) for belantamab mafodotin and combination treatments"}
• {"endpoint_text":"- Incidence of ocular findings on ophthalmic exam","definition_or_measurement_approach":"Incidence of ocular findings detected during ophthalmic examinations"}
• {"endpoint_text":"- Secondary end points Cohort Expansion: CBR according to the IMWG Response Criteria [Kumar, 2016]","definition_or_measurement_approach":"Clinical benefit rate (CBR) assessed according to IMWG Response Criteria"}
• {"endpoint_text":"- PFS","definition_or_measurement_approach":""}
• {"endpoint_text":"- DoR","definition_or_measurement_approach":""}
• {"endpoint_text":"- TTR","definition_or_measurement_approach":""}
• {"endpoint_text":"- Rates of: PR, VGPR; CR, sCR","definition_or_measurement_approach":"Response rates by category (PR, VGPR, CR, sCR) as per IMWG"}
• {"endpoint_text":"- OS","definition_or_measurement_approach":""}
• {"endpoint_text":"- Incidence of AEs, SAEs, AEs leading to discontinuation or dose reduction/delay, changes in clinical signs, and laboratory parameters.","definition_or_measurement_approach":"Incidence rates of AEs, SAEs, treatment discontinuations due to AEs, dose modifications, and changes in clinical/lab parameters"}
• {"endpoint_text":"- Incidence of AESIs for belantamab mafodotin.","definition_or_measurement_approach":"Incidence of predefined AESIs for belantamab mafodotin"}
• {"endpoint_text":"- Incidence of AESIs for the individual partner for each sub-study.","definition_or_measurement_approach":"Incidence of predefined AESIs for each combination partner in each sub-study"}
• {"endpoint_text":"- Incidence of ocular findings on ophthalmic exam for belantamab mafodotin.","definition_or_measurement_approach":"Incidence of ocular findings during ophthalmic exam specifically for belantamab mafodotin"}
• {"endpoint_text":"- Belantamab mafodotin and combination treatment’s plasma concentrations","definition_or_measurement_approach":"Plasma concentration measurements for belantamab mafodotin and combination treatments"}
• {"endpoint_text":"- Incidence and titers of ADAs against belantamab mafodotin and combination treatments, when measured","definition_or_measurement_approach":"Incidence and titers of ADAs when assays are performed"}

Sweden

Latest Decision Or Authorization Date

28-08-2024

Number Of Sites

1

Number Of Participants

8

France

Latest Decision Or Authorization Date

28-08-2024

Number Of Sites

3

Number Of Participants

22

Norway

Latest Decision Or Authorization Date

28-08-2024

Number Of Sites

1

Number Of Participants

8

Poland

Latest Decision Or Authorization Date

30-08-2024

Number Of Sites

4

Number Of Participants

24

Primary sponsor

Full Name

Glaxosmithkline Research & Development Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Syneos Health Inc.

Responsibilities

code: 4

Name

IQVIA Limited

Responsibilities

code: 13

Name

Fortrea Clinical Research Unit Limited

Responsibilities

code: 4

Name

Q Squared Solutions Limited

Responsibilities

code: 4

Third parties

• {"country":"Poland","full_name":"Clinops Tomasz Lusawa","duties_or_roles":"Renting equipment/medical devices to GSK clinical sites","organisation_type":"Industry"}
• {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Alliance Pharma Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Let Me Pay Sp. z o.o.","duties_or_roles":"Patient fee reimburstment","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Poland","full_name":"Komtur Polska Sp. z o.o.","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Certara USA Inc.","duties_or_roles":"code: 11","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Fortrea Clinical Research Unit Limited","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Menarini Silicon Biosystems Inc.","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Infinity Biologix LLC","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"code: 7","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"code: 7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Quanterix Corp.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Fm Richard Et Associes","duties_or_roles":"Reimbursement of patient fees // Payment of biological or radiological exams performed outside the sites","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"code: 13","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Quanterix Corp.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"code: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}