Clinical trial NCT06669247: A Study to Assess the Safety and Anti-Tumor Activity of REGN7945 in Combination With Linvoseltamab in Adult Participants With Relapsed/Refractory Multiple Myeloma
Official title: A First-in-Human (FIH) Phase 1/2 Study to Assess Safety, Tolerability, and Preliminary Anti-Tumor Activity of REGN7945, an Anti-CD38 x Anti-CD28 Costimulatory Bispecific Monoclonal Antibody, in Combination With Linvoseltamab, an Anti-BCMA x Anti-CD3 Bispecific Monoclonal Antibody, in Participants With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Multiple Myeloma
Keywords: R/RMM
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-11-01
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1: non-randomized dose escalation Phase 2: randomized dose expansion
Primary purpose: TREATMENT

Brief summary: This study is researching an experimental drug called REGN7945 in combination with another experimental drug called linvoseltamab, (also known as REGN5458) (each individually called a "study drug" or "study drugs" when combined).

This study is the first time REGN7945 will be tested in humans. Linvoseltamab has previously been studied by itself (without other cancer drugs) in participants who had advanced multiple myeloma that returned and needed to be treated again after several other therapies had failed.

The aim of the study is to see how safe, tolerable, and effective REGN7945 is when given in combination with linvoseltamab, compared with linvoseltamab alone.

The study is looking at several other research questions, including:

* What side effects may happen from taking the study drug(s)
* How many people treated with REGN7945 and linvoseltamab compared to linvoseltamab alone have improvement of their multiple myeloma and by how much
* How long people benefit from receiving REGN7945 in combination with linvoseltamab compared with linvoseltamab alone
* How much study drug(s) is in the blood at different times
* Whether the body makes antibodies against the study drugs(s) (which could make the study drug(s) less effective or could lead to side effects)
* If there is any change in pain and cancer-related symptoms, how well people are able to function, and their quality of life when taking the study drug(s)


Eligibility criteria: Key Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 as described in the protocol
2. Received at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 immunomodulatory imide drug (IMiD), and 1 proteasome inhibitor (PI) and have demonstrated disease progression on or after the last therapy, as defined in the protocol. Prior treatment with other BCMA directed immunotherapies, including BCMA CAR-T cells and BCMA antibody-drug conjugates (Phase 1 and 2), and with BCMA x CD3 bispecific antibodies (Phase 1 only), is allowed
3. Participants must have the measurable disease for response assessment as described in the protocol
4. Adequate hematologic, hepatic, and renal function as described in the protocol

Key Exclusion Criteria:

1. Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis (including myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
2. Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter
3. History of allogeneic stem cell transplantation within 6 months, or autologous stem cell transplantation within 12 weeks of the start of study treatment
4. Treatment with systemic corticosteroid treatment with more than 10 mg per day of prednisone or steroid equivalent within 72 hours of start of study drug
5. Participants who have known central nervous system (CNS) involvement with MM or known or suspected progressive multifocal leukoencephalopathy (PML), history of a neurocognitive condition or CNS disorder, or history of seizure within 12 months prior to study enrollment
6. Live or live attenuated vaccination within 28 days before first study drug administration with a vector that has replicative potential
7. Has received a COVID-19 vaccination within 1 week of planned start of study medication as described in the protocol
8. Myelodysplastic syndrome or another malignancy in the past 3 years, except for nonmelanoma skin cancer, in situ carcinoma, thyroid cancer, or low-risk early stage prostate adenocarcinoma, as described in the protocol
9. Significant cardiovascular disease as described in the protocol
10. Uncontrolled infection with HIV, Hep B or Hep C infection, or other uncontrolled infection, such as CMV, as described in the protocol
11. Known hypersensitivity to both allopurinol and rasburicase

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Primary outcomes:
measure: Incidence of dose limiting toxicities (DLTs) from the first dose of REGN7945 in combination with linvoseltamab
timeFrame: Up to 21 days
measure: Incidence of treatment emergent adverse events (TEAEs) during the treatment period with REGN7945 in combination with linvoseltamab
timeFrame: Up to 5 years
measure: Severity of TEAEs during the treatment period with REGN7945 in combination with linvoseltamab
timeFrame: Up to 5 years
measure: Very Good Partial Response (VGPR) or better as determined by the investigator using the International Myeloma Working Group (IMWG) response criteria in patients receiving combination therapy
timeFrame: Within 12 weeks of starting cycle 1
measure: VGPR or better as determined by the investigator using the IMWG response criteria in patients receiving linvoseltamab monotherapy
timeFrame: Within 12 weeks of starting cycle 1
measure: Partial Response (PR) or better as determined by the investigator using the IMWG response criteria in patients receiving combination therapy
timeFrame: Within 12 weeks of starting cycle 1
measure: PR or better as determined by the investigator using the IMWG response criteria in patients receiving linvoseltamab monotherapy
timeFrame: Within 12 weeks of starting cycle 1
Secondary outcomes:
measure: Incidence of TEAEs
timeFrame: Up to 5 years
measure: Severity of TEAEs
timeFrame: Up to 5 years
measure: Concentrations of REGN7945 in the serum
timeFrame: Up to 5 years
measure: Concentrations of linvoseltamab in the serum
timeFrame: Up to 5 years
measure: Incidence of anti-drug antibodies (ADA) to REGN7945
timeFrame: Up to 5 years
measure: Titer of ADA to REGN7945
timeFrame: Up to 5 years
measure: Incidence of ADA to linvoseltamab
timeFrame: Up to 5 years
measure: Titer of ADA to linvoseltamab
timeFrame: Up to 5 years
measure: Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) Global Health Status / Quality of Life (GHS/QoL)
timeFrame: Up to 5 years
measure: Change in EORTC QLQ-C30 Physical Functioning (PF)
timeFrame: Up to 5 years
measure: Change in EORTC QLQ-C30 Role Functioning (RF)
timeFrame: Up to 5 years
measure: Change in EORTC QLQ-C30 pain
timeFrame: Up to 5 years
measure: Change in EORTC QLQ-C30 fatigue
timeFrame: Up to 5 years
measure: Time to definitive deterioration in EORTC QLQ-C30 GHS/QoL
timeFrame: Up to 5 years
measure: Time to definitive deterioration in EORTC QLQ-C30 PF
timeFrame: Up to 5 years
measure: Time to definitive deterioration in EORTC QLQ-C30 RF
timeFrame: Up to 5 years
measure: Time to definitive deterioration in EORTC QLQ-C30 pain
timeFrame: Up to 5 years
measure: Time to definitive deterioration in EORTC QLQ-C30 fatigue
timeFrame: Up to 5 years
measure: Time to first improvement in EORTC QLQ-C30 GHS/QoL
timeFrame: Up to 5 years
measure: Time to first improvement in EORTC QLQ-C30 PF
timeFrame: Up to 5 years
measure: Time to first improvement in EORTC QLQ-C30 RF
timeFrame: Up to 5 years
measure: Time to first improvement in EORTC QLQ-C30 pain
timeFrame: Up to 5 years
measure: Time to first improvement in EORTC QLQ-C30 fatigue
timeFrame: Up to 5 years
measure: Change in EORTC QLQ-Multiple Myeloma Module (MY20) Disease Symptoms (DS)
timeFrame: Up to 5 years
measure: Change in EORTC QLQ-MY20 Treatment Side Effects (TSE)
timeFrame: Up to 5 years
measure: Change in EORTC QLQ-MY20 Body Image (BI)
timeFrame: UP to 5 years
measure: Change in EORTC QLQ-MY20 Future Perspective (FP)
timeFrame: Up to 5 years
measure: Time to definitive deterioration in EORTC QLQ-MY20 DS
timeFrame: Up to 5 years
measure: Time to definitive deterioration in EORTC QLQ-MY20 TSE
timeFrame: Up to 5 years
measure: Time to definitive deterioration in EORTC QLQ-MY20 BI
timeFrame: Up to 5 years
measure: Time to definitive deterioration in EORTC QLQ-MY20 FP
timeFrame: Up to 5 years
measure: Time to first improvement in EORTC QLQ-MY20 DS
timeFrame: Up to 5 years
measure: Time to first improvement in EORTC QLQ-MY20 TSE
timeFrame: Up to 5 years
measure: Time to first improvement in EORTC QLQ-MY20 BI
timeFrame: Up to 5 years
measure: Time to first improvement in EORTC QLQ-MY20 FP
timeFrame: Up to 5 years
measure: Change in EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Visual Analogue Score (VAS) (EQ-5D-5L VAS)
timeFrame: Up to 5 years
measure: Time to definitive deterioration in EQ-5D-5L VAS
timeFrame: Up to 5 years
measure: Time to first improvement in EQ-5D-5L VAS
timeFrame: Up to 5 days
measure: Patient-reported overall impact of treatment toxicity measured by Functional Assessment of Cancer Therapy (FACIT)-Item GP5
timeFrame: Up to 5 years
measure: Objective Response Rate (ORR) as measured by IMWG criteria as determined by the investigator
timeFrame: Up to 5 years
measure: Complete response (CR) rate as measured by IMWG criteria as determined by the investigator
timeFrame: Up to 5 years
measure: Duration of response (DOR) by IMWG criteria as determined by the investigator
timeFrame: Up to 5 years
measure: Progression Free Survival (PFS) as measured by IMWG criteria as determined by the investigator
timeFrame: Up to 5 years
measure: Achievement of Minimal Residual Disease (MRD) negative status (at 10^5) in participants in CR or better
timeFrame: Up to 5 years
measure: Overall survival (OS)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Wollongong
country: Australia
facility: Illawarra Cancer Care Centre
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Fitzroy
country: Australia
facility: St Vincent's Hospital - Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: