Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat, Lenalidomide, and Dexamethasone in Participants With RRMM
Not Applicable
Active, not recruiting
- Conditions
- Multiple Myeloma
- Interventions
- Registration Number
- NCT07150091
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
The primary purpose is to determine the safety and tolerability of belantamab mafodotin in combination with nirogacestat, lenalidomide, and dexamethasone, and to establish the recommended Phase 2 dose for combination treatment to explore in the cohort expansion (CE) phase in participants with RRMM. This study is a sub study of the Master protocol (NCT04126200).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 20
Inclusion Criteria
- 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 ophthalmalogical steroids.
- Participants with platelets value for Adequate Organ System Function is ≥75 × 10^9/L.
Exclusion Criteria
- 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.
- 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. For participants receiving nirogacestat, HIV drugs that are strong Cytochrome P450 3A4 (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.
- Participants with uncontrolled small and/or large intestinal disease.
- Participants with uncontrolled skin disease.
- Participants with any condition causing hypophosphatemia, hypokalemia or hypomagnesemia which is refractory to electrolyte replacement.
- Participants with previous administration of a gamma secretase inhibitor.
- Participants with concomitant administration of a strong CYP3A4 inhibitor or inducer.
- Participants with active or history of venous thromboembolism within the past 3 months.
- Participants with evidence of active mucosal or internal bleeding.
- Participants with contraindications to or are unwilling to undergo protocol-required anti-thrombotic prophylaxis or unable to tolerate antithrombotic prophylaxis.
- Participants who discontinued prior treatment with lenalidomide due to intolerable adverse events.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Belantamab mafodotin + Nirogacestat + Lenalidomide + Dexamethasone Belantamab mafodotin - Belantamab mafodotin + Nirogacestat + Lenalidomide + Dexamethasone Nirogacestat - Belantamab mafodotin + Nirogacestat + Lenalidomide + Dexamethasone Lenalidomide - Belantamab mafodotin + Nirogacestat + Lenalidomide + Dexamethasone Dexamethasone -
- Primary Outcome Measures
Name Time Method Dose Exploration (DE) Phase: Number of participants with dose limiting toxicities (DLTs) Up to 21 days DE Phase: Number of participants with adverse events (AEs) Up to approximately 143 weeks DE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry, and urinalysis lab parameters Up to approximately 143 weeks Cohort Expansion (CE) Phase: Overall Response Rate (ORR) Up to approximately 143 weeks ORR is defined as the percentage of participants with a confirmed Partial response (PR) or better as the best overall response (BOR), according to the International Myeloma Working Group (IMWG) Response Criteria.
- Secondary Outcome Measures
Name Time Method DE Phase: Overall Response Rate Up to approximately 242 weeks ORR is defined as the percentage of participants with confirmed PR or better as BOR, according to the IMWG Response Criteria.
CE Phase: Clinical Benefit Rate (CBR) Up to approximately 242 weeks CBR is defined as the percentage of participants with a confirmed minimal response (MR) or better as BOR, according to IMWG response criteria.
DE Phase: Number of participants achieving Partial Response (PR) Up to approximately 242 weeks Number of participants with PR according to IMWG criteria will be analysed.
CE Phase: Number of participants achieving PR Up to approximately 242 weeks Number of participants with PR according to IMWG criteria will be analysed.
DE Phase: Number of participants achieving Very Good Partial Response (VGPR) Up to approximately 242 weeks Number of participants with VGPR according to IMWG criteria will be analysed.
CE Phase: Number of participants achieving VGPR Up to approximately 242 weeks Number of participants with VGPR according to IMWG criteria will be analysed.
DE Phase: Number of participants achieving Complete Response (CR) Up to approximately 242 weeks Participants with CR according to IMWG criteria will be analysed.
DE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments Up to approximately 242 weeks CE Phase: Number of participants achieving CR Up to approximately 242 weeks Participants with CR according to IMWG criteria will be analysed.
CE Phase: Belantamab mafodotin concentrations when administered in combination with anti-cancer treatments Up to approximately 242 weeks DE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin Up to approximately 242 weeks DE Phase: Number of participants achieving Stringent Complete Response (sCR) Up to approximately 242 weeks Participants with sCR according to IMWG criteria will be analysed.
CE Phase: Number of participants achieving sCR Up to approximately 242 weeks Participants with sCR according to IMWG criteria will be analysed.
CE Phase: Nirogacestat concentration when administered in combination with belantamab mafodotin Up to approximately 242 weeks DE Phase: Lenalidomide concentration when administered in combination with belantamab mafodotin Up to approximately 242 weeks CE Phase: Lenalidomide concentration when administered in combination with belantamab mafodotin Up to approximately 242 weeks DE Phase: Dexamethasone concentration when administered in combination with belantamab mafodotin Up to approximately 242 weeks CE Phase: Dexamethsone concentration when administered in combination with belantamab mafodotin Up to approximately 242 weeks DE Phase: Number of participants with anti-drug antibodies (ADAs) against belantamab mafodotin Up to approximately 242 weeks CE Phase: Titre of ADAs against belantamab mafodotin Up to approximately 242 weeks DE Phase: Titre of (ADAs) against belantamab mafodotin Up to approximately 242 weeks CE Phase: Number of participants with ADAs against belantamab mafodotin Up to approximately 242 weeks DE Phase: Number of participants with AESI for Lenalidomide Up to approximately 242 weeks DE Phase: Number of participants with adverse events of special interest (AESI) for belantamab mafodotin Up to approximately 242 weeks CE Phase: Number of participants with AESI for belantamab mafodotin Up to approximately 242 weeks DE Phase: Number of participants with AESI for Nirogacestat Up to approximately 242 weeks CE Phase: Number of participants with AESI for Nirogacestat Up to approximately 242 weeks CE Phase: Number of participants with AESI for Lenalidomide Up to approximately 242 weeks CE Phase: Duration of response (DoR) Up to approximately 242 weeks DoR is defined as the time from first documented evidence of confirmed PR or better until progressive disease per IMWG or death due to progressive disease among participants who achieve confirmed partial response or better.
DE Phase: Number of participants with AESI for Dexamethasone Up to approximately 242 weeks CE Phase: Number of participants with AESI for Dexamethasone Up to approximately 242 weeks DE Phase: Number of participants with abnormal ocular findings on ophthalmic examination Up to approximately 242 weeks CE Phase: Number of participants with abnormal ocular findings on ophthalmic examination Up to approximately 242 weeks CE Phase: Progression-free survival (PFS) Up to approximately 242 weeks 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.
CE Phase: Number of participants with AE leading to dose reduction or delay Up to approximately 242 weeks CE Phase: Time to response (TTR) Up to approximately 242 weeks TTR is defined as the time between the date of randomization and the first documented evidence of response (confirmed PR or better), among participants who achieve a response (confirmed PR or better).
CE Phase: Overall survival (OS) Up to approximately 242 weeks OS is defined as the time from randomization until death due to any cause.
CE Phase: Number of participants with AEs and SAEs Up to approximately 242 weeks CE Phase: Number of participants with AEs leading to discontinuation Up to approximately 242 weeks CE Phase: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis lab parameters Up to approximately 242 weeks
Trial Locations
- Locations (1)
GSK Investigational Site
🇰🇷Ulsan, South Korea
GSK Investigational Site🇰🇷Ulsan, South Korea