Relapsed/Refractory Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: GSK2857916
Product Code: GSK2857916
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: belantamab mafodotin
CAS Number: N/A
Current Sponsor code: GSK2857916
Other descriptiv
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the criteria in Section 5.1 and Section 5.2 apply. In addition, participants must fulfil additional inclusion/exclusion criteria for at least 1 partner combination sub-study. Criteria for each individual sub-study can be found in the respective sub-study protocol section. Age 1. Participant must be 18 years of age inclusive or older, at the time of signing the informed consent. Note: if country/site age requirements for consent differ, the more stringent (e.g., higher age) restriction will be required for that country/site. Type of Participant and Disease Characteristics 2. Participants who have histologically or cytologically confirmed diagnosis of MM, as defined by the International Myeloma Working Group (IMWG, [Rajkumar, 2014]). 3. Participants who have been treated with at least 3 prior lines of anti-myeloma treatments including an immunomodulating agent (eg. lenalidomide), a proteasome inhibitor (eg. bortezomib) and an anti-CD38 monoclonal antibody. Lines of therapy are defined by consensus panel of the International Myeloma Workshop [Rajkumar, 2011a]. 4. Participants with a 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. 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. Measurable disease defined as at least 1 of the following: • Serum M-protein =0.5 g/dL (=5 g/L) • Urine M-protein =200 mg/24 hours • Serum free light chain (FLC) assay: Involved FLC level =10 mg/dL (=100 mg/L) and an abnormal serum FLC ratio (1.65). 7. Have organ system functions as defined by the laboratory assessments in Table 15 in the protocol. 8. Participants who have tested positive for HBcAb can be enrolled if the following criteria are met: - Serology result: HBcAb+, HBsAg- - Screening: HBV DNA undetectable - During Study Treatment: Monitoring per protocol (Section 6.6.5), Initiating antiviral treatment if HBV DNA becomes detectable. 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. Participants who are currently receiving physiological doses oral steroids (<10mg/day), inhaled steroids or ophthalmalogical steroids are allowed on study. Sex 11. Male or female reference section 12.7 removed Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies (see Appendix 7 for further details). a. Male Participants: Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in the clinical studies. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 6 months after the last dose of study intervention to allow for clearance of any altered sperm: Refrain from donating sperm PLUS either: • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term a
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1. Symptomatic amyloidosis, active ‘polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes’ (POEMS) syndrome, current or past diagnosis of plasma cell leukemia. 2. 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. 3. Current corneal epithelial disease except mild punctate keratopathy. 4. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if participant otherwise meets entry criteria. 5. Malignancies other than disease under study are excluded, except for any other malignancy from which the participant has been disease-free for more than 2 years and, in the opinion of the principal investigators and GSK Medical Director, will not affect the evaluation of the effects of this clinical trial treatment on the currently targeted malignancy (MM). • Participants with curatively treated non-melanoma skin cancer are not excluded. 6. Evidence of cardiovascular risk including any of the following: a. Evidence of current clinically significant untreated arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobiz Type II) or 3rd degree atrioventricular (AV) block. b. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting or bypass grafting, all within three months of Screening. c. Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system d. Uncontrolled hypertension. 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. 8. Active infection requiring antibiotic, antiviral, or antifungal treatment. 9. Known HIV infection unless the participant can meet all of the criteria stated in the protocol. 10. Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction. 11. Presence of hepatitis B surface antigen (HBsAg) at screening or within prior history. 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. Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if confirmatory negative Hepatitis C RNA test is obtained. Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required to undergo Hepatitis C RNA testing. 13. 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 are eligible, provided they fulfil criteria given in Table 15. Prior/Concomitant Therapy 14. Patients who have rec
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose Exploration Reference to GSK'916 has been removed and replaced with belantamab mafodotin. 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 CE Phase in participants with RRMM Cohort Expansion To assess the clinical activity of belantamab mafodotin at the RP2D in combination with anti-cancer treatments compared to GSK’916 (belantamab mafodotin) monotherapy in participants with RRMM;Secondary Objective: DE Key Secondary Reference to GSK'916 has been removed and replaced with belantamab mafodotin To evaluate the clinical measures of efficacy of belantamab mafodotin and combination treatments in each sub-study in participants with RRMM DE Secondary To further evaluate the clinical measures of efficacy of belantamab mafodotin and combination treatments in each sub-study in participants with RRMM CE Secondary To further assess clinical activity of combination treatments with belantamab mafodotin at the RP2D compared with monotherapy within each sub-study in participants with RRMM Refer to the protocol for remaining Dose Exploration & Cohort Expansion secondary points.;Primary end point(s): Dose Exploration - Percentage (number) of participants with dose limiting toxicities (DLTs) - Percent of subjects with AEs, changes in clinical signs and laboratory parameters Cohort Expansion Overall Response Rate (ORR), according to the International Myeloma Working Group (IMWG) Response Criteria [Kumar, 2016]. ;Timepoint(s) of evaluation of this end point: From when the first participant initiated treatment until the last participant has received 3 cycles of study drug(s). Cohort Expansion: 6 months after the last participant is dosed for each sub-study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Dose Exploration • Clinical activity measured as Overall Response Rate (ORR), according to the International Myeloma Working Group (IMWG) Response Criteria [Kumar, 2016] • Rates of: - Partial Response (PR); - Very Good Partial Response (VGPR); - Complete Response (CR); - stringent Complete Response (sCR) • The following text GSK'916 observed concentrations up to Cycle 6 has been replaced with Belantamab mafodotin observed concentrations • Anti-cancer combination treatment’s observed concentration • Incidence and titers of ADAs against GSK’916 (belantamab mafodotin) and combination treatments, when measured. • Incidence of AEs of special interest for belantamab mafodotin • Incidence of AEs of special interest for combination treatments • Incidence of ocular findings on ophthalmic exam Cohort Expansion • Assess the Clinical Benefit Rate (CBR) [Kumar, 2016] • PFS • DoR • TTR • Rates of: PR, VGPR, CR, sCR • OS • Incidence of adverse events (AEs), Serious Adverse Events (SAEs), AEs leading to discontinuation or dose reduction/delay, changes in clinical signs, and laboratory parameters • Incidence of AEs of special interest for belantamab mafodotin •Incidence of AESIs for the individual partner for each sub-study • Incidence of ocular findings on ophthalmic exam for belantamab mafodotin • Belantamab mafodotin and combination treatments’ plasma concentrations. • Incidence and titers of ADAs against belantamab mafodotin and combination treatments, when measured.;Timepoint(s) of evaluation of this end point: From when the first participant initiated treatment until the last participant has received 3 cycles of study drug(s). Cohort Expansion: 6 months after the last participant is dosed for each sub-study. | — |
Countries
Australia, Brazil, Canada, Czechia, France, Germany, Greece, Israel, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Russian Federation, Spain, Sweden, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed