Relapsed/Refractory Multiple MyelomaPhase 1/2NCT06160609
Platform Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With aOX40 (GSK3174998) in Participants With RRMM
A Phase 1/2 study testing Belantamab Mafodotin and GSK3174998 in people with Relapsed/Refractory Multiple Myeloma, run by GlaxoSmithKline at 3 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory Multiple Myeloma
- What is being tested?
- Belantamab Mafodotin and GSK3174998
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 3 sitesin 3 countries
- Study dates
- 7 Oct 2019to 9 Jan 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: 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
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).
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Being tested
- Belantamab Mafodotin, GSK3174998
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belantamab MafodotinDrug
Also called GSK2857916
Belantamab Mafodotin will be administered.
GSK3174998Drug
Also called aOX40
GSK3174998 will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Belantamab mafodotin + GSK3174998 | Experimental | Not described Receives: Drug: Belantamab Mafodotin; Drug: GSK3174998 |
What is being measured
The primary outcome is the main question the study is designed to answer.
DE Phase: Number of Participants With Dose Limiting Toxicities (DLT)
Criteria for dose-limiting toxicity (DLT) included hematologic indicators such as Grade 3-5 febrile neutropenia and thrombocytopenia with bleeding. Non-hematologic criteria, excluding corneal toxicity, comprise Grade 3-5 toxicities, with exceptions for manageable nausea, vomiting, or diarrhea, controlled Grade 3 hypertension, and events linked to disease progression. Tumor lysis syndrome (TLS) of Grade 3 or 4, successfully managed within 7 days without end-organ damage, is considered. Corneal toxicity, assessed by the GSK corneal grading scale at Grade 4, is a DLT. Other organ-specific toxicities, notably liver toxicity meeting GSK stopping criteria, also qualify as DLTs.
Measured: Up to 21 days
DE Phase: Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Measured: Up to 170 weeks
DE Phase: Number of Participants With Worst-Case Hematology Results by Maximum Grade Increase Post - Baseline Relative to Baseline
Blood samples were collected for the analysis of following hematology parameters: eosinophils, anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, leukocytosis and white blood cell decreased. The laboratory parameters were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3: severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increase to G1, G2 and G3 are presented.
Measured: Baseline (Day 1) and up to 170 weeks
DE Phase: Number of Participants With Worst-Case Chemistry Results by Maximum Grade Increase Post - Baseline Relative to Baseline
Blood samples were collected for the analysis of following chemistry parameters: Hypoglycemia, hypoalbuminemia, alkaline phosphatase (ALP) increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatine kinase (CPK) increased, creatinine increased, gamma glutamyl transferase (GGT) increased, hyperkalemia, blood lactate dehydrogenase (LDH) increased, hypermagnesemia, hypomagnesemia, hypernatremia, hypercalcemia, hypocalcemia and Serum OR Plasma Glomerular Filtration Rate (GFR) from creatinine adjusted for body surface area (BSA) SA (mL/sec/1.73m^2)/chronic kidney disease. The laboratory parameters were graded according to CTCAE version 5. G1: mild; G2: moderate; G3: severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increase to G1, G2 and G3 are presented.
Measured: Baseline (Day 1) and up to 170 weeks
Cohort Expansion (CE) Phase: Overall Response Rate (ORR)
Overall Response Rate (ORR) was defined as the percentage of participants with a confirmed PR or better as the best overall response (i.e., Partial Response [PR], Very Good Partial Response [VGPR], Complete Response [CR], and stringent Complete Response [sCR]), as assessed by the investigator per international myeloma working group (IMWG) (2016). CR defined as negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR defined as CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR defined as serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 h; PR defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 h.
Measured: Up to 170 weeks
Secondary outcomes (33)
DE Phase: Overall Response Rate (ORR)
ORR was 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] and stringent complete response [sCR]), according to the International Myeloma Working Group (IMWG) Response Criteria. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 h; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 h.
Measured: Up to 170 weeks
CE Phase: Clinical Benefit Rate (CBR)
Clinical benefit rate was defined as the percentage of participants with a confirmed minimal response (MR) or better according to the IMWG Response Criteria. MR is >= 25% but < 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50-89%.
Measured: Up to 170 weeks
DE Phase: Percentage of Participants Achieving Stringent Complete Response (SCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)
Partial Response [PR], Very Good Partial Response [VGPR], Complete Response [CR], and stringent Complete Response [sCR] as assessed by the investigator per IMWG (2016). CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 h; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 h.
Measured: Up to 170 weeks
CE Phase: Percentage of Participants Achieving SCR, CR, VGPR and PR
Partial Response [PR], Very Good Partial Response [VGPR], Complete Response [CR], and stringent Complete Response [sCR] as assessed by the investigator per IMWG (2016). CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 h; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 h.
Measured: Up to 170 weeks
DE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC)
Blood samples were collected for PK analysis of belantamab mafodotin Antibody-Drug Conjugate (ADC).
Measured: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
CE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC)
Blood samples were collected for PK analysis of Belantamab Mafodotin Antibody-Drug Conjugate (ADC).
Measured: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
DE Phase: Plasma Concentration of Belantamab Mafodotin Total Antibody
Blood samples were collected for PK analysis of Belantamab mafodotin total antibody.
Measured: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
CE Phase: Plasma Concentration of Belantamab Mafodotin Plasma Total Antibody
Blood samples were collected for PK analysis of Belantamab mafodotin plasma total antibody.
Measured: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
DE Phase: Plasma Concentrations of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)
Blood samples were collected for PK analysis of belantamab mafodotin cys- monomethyl auristatin-F (cys-mcMMAF).
Measured: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
CE Phase: Plasma Concentrations of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)
Blood samples were collected for PK analysis of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)
Measured: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
DE Phase: OX40 Concentration When Administered in Combination With Belantamab Mafodotin
Blood samples were collected for PK analysis of OX40 when administered intravenously in combination with belantamab mafodotin.
Measured: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
CE Phase: OX40 Concentration When Administered in Combination With Belantamab Mafodotin
Blood samples were collected for PK analysis of OX40 when administered intravenously in combination with belantamab mafodotin.
Measured: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
DE Phase: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were tested in screening assay, and positive samples were further characterized for antibody titers.
Measured: Up to 170 weeks
CE Phase: Number of Participants With Post-baseline Positive ADAs Against Belantamab Mafodotin
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were tested in screening assay, and positive samples were further characterized for antibody titers.
Measured: Up to 170 weeks
DE Phase: Number of Participants With Post-baseline Positive ADAs Against OX40
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were tested in screening assay, and positive samples were further characterized for antibody titers.
Measured: Up to 170 weeks
CE Phase: Number of Participants With Post-baseline Positive ADAs Against OX40
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were tested in screening assay, and positive samples were further characterized for antibody titers.
Measured: Up to 170 weeks
DE Phase: Concentration of ADAs Against Belantamab Mafodotin
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were to be further tested in screening assay, and positive samples were further to be characterized for antibody titers.
Measured: Up to 170 weeks
CE Phase: Concentration of ADAs Against Belantamab Mafodotin
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were to be further tested in screening assay, and positive samples were further to be characterized for antibody titers.
Measured: Up to 170 weeks
DE Phase: Concentration of ADAs Against OX40 When Administered in Combination With Belantamab Mafodotin
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were to be further tested in screening assay, and positive samples were further to be characterized for antibody titers.
Measured: Up to 170 weeks
CE Phase: Concentration of ADAs Against OX40 When Administered in Combination With Belantamab Mafodotin
Serum samples collected for the analysis of the presence of ADAs using validated immunoassays. All samples were to be further tested in screening assay, and positive samples were further to be characterized for antibody titers.
Measured: Up to 170 weeks
DE Phase: Number of Participants With Adverse Events of Special Interest (AESI)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Adverse Events of Special Interest (whether serious or non serious) were collected.
Measured: Up to 170 weeks
CE Phase: Number of Participants With AESI
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function.
Measured: Up to 170 weeks
DE Phase: Number of Participants With Any Corneal Events by Maximum Grade as Per CTCAE Grade
The corneal events were graded according to CTCAE version 5. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Results are presented for number of participants with any corneal events by maximum grade as per CTCAE grade.
Measured: Up to 170 weeks
CE Phase: Number of Participants With Any Corneal Events by Maximum Grade as Per CTCAE Grade
Corneal Events were examined.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: Up to 170 weeks
CE Phase: Overall Survival (OS)
OS is defined as the time from randomization until death due to any cause.
Measured: Up to 170 weeks
CE Phase: Number of Participants With AEs and SAEs
AEs and SAEs were collected.
Measured: Up to 170 weeks
CE Phase: Number of Participants With AEs Leading to Discontinuation
Number of participants with AEs leading to discontinuation were evaluated.
Measured: Up to 170 weeks
CE Phase: Number of Participants With Dose Reduction or Delay
Number of participants with dose reduction or delay were evaluated.
Measured: Up to 170 weeks
CE Phase: Number of Participants With Clinically Significant Changes in Hematology Lab Parameters
Blood samples were collected for the analysis of following hematology parameters: eosinophils, anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, leukocytosis and white blood cell decreased. The laboratory parameters were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3: severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade.
Measured: Up to 170 weeks
CE Phase: Number of Participants With Clinically Significant Changes in Clinical Chemistry Lab Parameters
Blood samples were collected for the analysis of following chemistry parameters: Hypoglycemia, hypoalbuminemia, alkaline phosphatase (ALP) increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatine kinase (CPK) increased, creatinine increased, gamma glutamyl transferase (GGT) increased, hyperkalemia, blood lactate dehydrogenase (LDH) increased, hypermagnesemia, hypomagnesemia, hypernatremia, hypercalcemia, hypocalcemia and chronic kidney disease. The laboratory parameters were graded according to CTCAE version 5. G1: mild; G2: moderate; G3: severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade.
Measured: Up to 170 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2023
- Study start7 Oct 2019
- Primary completion9 Jan 2023
- Study completion9 Jan 2023
Why it stopped: The study was terminated due to lack of efficacy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Relapsed/Refractory Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06160609
- Sponsor's protocol ID
- 208887 Sub Study 1
- Other IDs
- 2019-001138-32, 2019
- Status last verified
- Feb 2024
- First submitted
- 29 Nov 2023
- Last updated
- 12 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06160609
- Acronym / sponsor ID
- 208887 Sub Study 1
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to lack of efficacy.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 7 Oct 2019 (actual)
- Primary completion
- 9 Jan 2023 (actual)
- Study completion
- 9 Jan 2023 (actual)
- First posted
- 7 Dec 2023 (actual)
- Results
- Posted 12 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Belantamab mafodotin + GSK3174998 | Experimental | Drug: Belantamab Mafodotin, Drug: GSK3174998 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Belantamab MafodotinAlso: GSK2857916Belantamab Mafodotin will be administered. | Drug | Belantamab mafodotin + GSK3174998 |
| GSK3174998Also: aOX40GSK3174998 will be administered. | Drug | Belantamab mafodotin + GSK3174998 |
Primary outcome
DE Phase: Number of Participants With Dose Limiting Toxicities (DLT)
Time frame: Up to 21 days
Criteria for dose-limiting toxicity (DLT) included hematologic indicators such as Grade 3-5 febrile neutropenia and thrombocytopenia with bleeding. Non-hematologic criteria, excluding corneal toxicity, comprise Grade 3-5 toxicities, with exceptions for manageable nausea, vomiting, or diarrhea, controlled Grade 3 hypertension, and events linked to disease progression. Tumor lysis syndrome (TLS) of Grade 3 or 4, successfully managed within 7 days without end-organ damage, is considered. Corneal toxicity, assessed by the GSK corneal grading scale at Grade 4, is a DLT. Other organ-specific toxicities, notably liver toxicity meeting GSK stopping criteria, also qualify as DLTs.
DE Phase: Number of Participants With Adverse Events (AEs)
Time frame: Up to 170 weeks
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
DE Phase: Number of Participants With Worst-Case Hematology Results by Maximum Grade Increase Post - Baseline Relative to Baseline
Time frame: Baseline (Day 1) and up to 170 weeks
Blood samples were collected for the analysis of following hematology parameters: eosinophils, anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, leukocytosis and white blood cell decreased. The laboratory parameters were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. Grade 1 (G1): mild; Grade 2 (G2): moderate; Grade 3 (G3: severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increase to G1, G2 and G3 are presented.
DE Phase: Number of Participants With Worst-Case Chemistry Results by Maximum Grade Increase Post - Baseline Relative to Baseline
Time frame: Baseline (Day 1) and up to 170 weeks
Blood samples were collected for the analysis of following chemistry parameters: Hypoglycemia, hypoalbuminemia, alkaline phosphatase (ALP) increased, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood bilirubin increased, creatine kinase (CPK) increased, creatinine increased, gamma glutamyl transferase (GGT) increased, hyperkalemia, blood lactate dehydrogenase (LDH) increased, hypermagnesemia, hypomagnesemia, hypernatremia, hypercalcemia, hypocalcemia and Serum OR Plasma Glomerular Filtration Rate (GFR) from creatinine adjusted for body surface area (BSA) SA (mL/sec/1.73m^2)/chronic kidney disease. The laboratory parameters were graded according to CTCAE version 5. G1: mild; G2: moderate; G3: severe or medically significant. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Any worst-case post baseline increase to G1, G2 and G3 are presented.
Cohort Expansion (CE) Phase: Overall Response Rate (ORR)
Time frame: Up to 170 weeks
Overall Response Rate (ORR) was defined as the percentage of participants with a confirmed PR or better as the best overall response (i.e., Partial Response [PR], Very Good Partial Response [VGPR], Complete Response [CR], and stringent Complete Response [sCR]), as assessed by the investigator per international myeloma working group (IMWG) (2016). CR defined as negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR defined as CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR defined as serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 h; PR defined as ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 h.
33 secondary outcomes
DE Phase: Overall Response Rate (ORR)
Time frame: Up to 170 weeks
CE Phase: Clinical Benefit Rate (CBR)
Time frame: Up to 170 weeks
DE Phase: Percentage of Participants Achieving Stringent Complete Response (SCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)
Time frame: Up to 170 weeks
CE Phase: Percentage of Participants Achieving SCR, CR, VGPR and PR
Time frame: Up to 170 weeks
DE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC)
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
CE Phase: Plasma Concentrations of Belantamab Mafodotin Antibody-Drug Conjugate (ADC)
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
DE Phase: Plasma Concentration of Belantamab Mafodotin Total Antibody
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
CE Phase: Plasma Concentration of Belantamab Mafodotin Plasma Total Antibody
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
DE Phase: Plasma Concentrations of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
CE Phase: Plasma Concentrations of Belantamab Mafodotin Cys- Monomethyl Auristatin-F (Cys-mcMMAF)
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
DE Phase: OX40 Concentration When Administered in Combination With Belantamab Mafodotin
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
CE Phase: OX40 Concentration When Administered in Combination With Belantamab Mafodotin
Time frame: Up to Day 1 (End of Infusion) of Cycle 6 (Each Cycle consist of 21 days)
DE Phase: Number of Participants With Post-baseline Positive Anti-drug Antibodies (ADAs) Against Belantamab Mafodotin
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Post-baseline Positive ADAs Against Belantamab Mafodotin
Time frame: Up to 170 weeks
DE Phase: Number of Participants With Post-baseline Positive ADAs Against OX40
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Post-baseline Positive ADAs Against OX40
Time frame: Up to 170 weeks
DE Phase: Concentration of ADAs Against Belantamab Mafodotin
Time frame: Up to 170 weeks
CE Phase: Concentration of ADAs Against Belantamab Mafodotin
Time frame: Up to 170 weeks
DE Phase: Concentration of ADAs Against OX40 When Administered in Combination With Belantamab Mafodotin
Time frame: Up to 170 weeks
CE Phase: Concentration of ADAs Against OX40 When Administered in Combination With Belantamab Mafodotin
Time frame: Up to 170 weeks
DE Phase: Number of Participants With Adverse Events of Special Interest (AESI)
Time frame: Up to 170 weeks
CE Phase: Number of Participants With AESI
Time frame: Up to 170 weeks
DE Phase: Number of Participants With Any Corneal Events by Maximum Grade as Per CTCAE Grade
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Any Corneal Events by Maximum Grade as Per CTCAE Grade
Time frame: Up to 170 weeks
CE Phase: Progression-free Survival (PFS)
Time frame: Up to 170 weeks
CE Phase: Duration of Response (DoR)
Time frame: Up to 170 weeks
CE Phase: Time to Response (TTR)
Time frame: Up to 170 weeks
CE Phase: Overall Survival (OS)
Time frame: Up to 170 weeks
CE Phase: Number of Participants With AEs and SAEs
Time frame: Up to 170 weeks
CE Phase: Number of Participants With AEs Leading to Discontinuation
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Dose Reduction or Delay
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Clinically Significant Changes in Hematology Lab Parameters
Time frame: Up to 170 weeks
CE Phase: Number of Participants With Clinically Significant Changes in Clinical Chemistry Lab Parameters
Time frame: Up to 170 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Belantamab Mafodotin and GSK3174998 in people with Relapsed/Refractory Multiple Myeloma, run by GlaxoSmithKline at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia, Canada, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DE Phase: Number of Participants With Dose Limiting Toxicities (DLT) (time frame: Up to 21 days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2024.