Short summary

An open label, phase two, prospective, non-randomized, sponsor-initiated single center feasibility study of elranatamab to 20 patients with relapsed multiple myeloma exposed to at least one proteasome inhibitor, one immunomodulatory agent (IMID), and one anti CD-38 antibody. The intervention of the study is self-administration of elranatamab by the patient, thereby changing the administration from an outpatient setting to a home setting in cycle 2-6 (28 days per cycle).

Rationale

There is an unmet need in the treatment of multiple myeloma as patients have a very short life expectancy after they have been treated with an IMID, a proteasome inhibitor, and an anti CD 38 antibody. Bispecific CD3xBCMA antibodies may be part of the solution to this unmet need as they have demonstrated very high response rates in heavily pretreated patients. Elranatamab is one of two bispecific CD3xBCMA antibodies that are conditionally approved by EMA for treatment in patients with MM. As elranatamab is administered weekly until progression patients have multiple visits to the outpatient clinic, meaning that they spend a substantial amount of time on transport, and that they are continuously exposed to potential infections, which has proven to be one of the most common and severe side effects to CD3xBCMA bispecifics. During the COVID-19 pandemic, we all learned that social distance is the best way to avoid infections. Patients with MM has a severely reduced immune system, so transporting them weekly to a hospital, to be placed a few hours in an outpatient clinic with other sick patients may not be the optimal way to avoid potential lethal infection. The primary objective of this study is to investigate if partly self-administration of elranatamab in the patients' own home can be conducted in in a safe manner and perhaps also reduce the risk of infection.

Description of the cohort

20 patients with relapsed multiple myeloma exposed to at least one proteasome inhibitor, one immunomodulatory agent (IMID), and one anti CD-38 antibody is planned for inclusion in the study. Physicians in the outpatient clinic at the department of hematology will identify potential candidates. Patients and caregivers will be invited to participate in the study, if they fulfil the inclusion and exclusion criteria. Due to the risk of CRS, patients will be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose. If no CRS, ICANS, or other events incompatible with treatment in the outpatient clinic occurs, D8, D15, and D22 will be administered in the outpatient clinic and will include training of the patients in self-administration. Patients must be assessed according to criteria for home treatment by the treating physician before proceeding to outpatient treatment. In cycle 2 to cycle 6, patients will administer the treatment themselves in the outpatient clinic D1 and at home D8, D15, and D22.

Data and biological material

To meet the first primary endpoint of the study, number of discarded doses, planned doses administered at home, and doses diverted from the patients' homes to the outpatient clinic will be collected. Moreover, data on AEs/SAEs will continuously be collected throughout the study. In particular, focus will be directed towards the occurrence of infections, CRS, and ICANS. At inclusion, data on age, gender, marital status, educational level, employment status, PS, R-ISS, ISS, vital signs, myeloma type, renal and liver function, concomitant medication (CM), weight, number of previous lines of treatment, and response to previous lines of treatment will be registered in an electronic case report form (eCRF). Results of standard-of-care tests or examinations performed prior to obtaining informed consent and within 28 days prior to C1D1 may be used. These tests do not need to be repeated for screening. At inclusion, patients will further be physically examined and cognitively tested, which will include a writing test and a test of their ability to recognize known pictures. Finally, patients must complete the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), the EORTC Multiple Myeloma Quality of Life Questionnaire (QLQ-MY20), and the Functional Assessment of Cancer Therapy - Cognitive (FACT Cognitive) questionnaires electronically. Caregivers will be asked to complete the Family Reported Outcome Measure (FROM-16). If the caregiver do not attend the patient to the outpatient clinic, the patient will be handed out the questionnaire in paper form to bring home. Upon completion, the questionnaire must be returned to the study team in a pre-paid envelope. During planned hospitalization in cycle 1, patients will be continuously examined, and data on PS, vital signs, results of blood samples, CM, AEs, and results of CRS and ICANS screening will be collected. Similar data will be collected at C1D8, C1D15, and C1D22. Starting from cycle 2, data on location of administration will be collected. Specifically, redirected administrations and discarded doses will be registered. When patients attend the outpatient clinic at D1, they will be physically examined, and data on PS, vital signs, results of blood samples, CM, AEs, and weight will be collected. Further, they will be asked to complete the FACT Cognitive questionnaire. Moreover, in cycle 3, they will be asked to complete EORTC QLQ-C30 and EORTC QLQ-MY20 as well; caregivers will be asked to complete FROM-16, if necessary in paper form at home. At D1 (in the outpatient clinic) and D8 (at home) in cycle 2-6, patients, caregivers, nurses, and physicians in the outpatient clinic must register their time spent on the administration. For patients and caregivers, this includes waiting time and time spent on transportation. Further, they should register their mode of transportation and if they have had any need for taking time off from work due to the planned administration. For nurses and physicians, registrations include both administrative activities and time spent with the patient. Before each home administration (D8, D15, and D22), patients will receive an electronic questionnaire on their physical and cognitive condition. They will be asked about any side effects or sickness since their last treatment. In specific, they will be asked if they have or have had a fever (they will be instructed in measuring their temperature before every injection), if they have experienced dizziness, or if they have received any antibiotics. The questionnaire must be completed two days prior to the administration. On the day of treatment, a specialized nurse from the outpatient clinic will assess the responses and call the patient in the morning to make sure there are no side effects incompatible with treatment. In Part 1, patients must register if they have had any unplanned contact with the healthcare system (e.g. the hospital or their GP). For this purpose, they will automatically be contacted electronically each week through the app My Hospital, and if they register any unplanned contacts, a study nurse will contact them for clarification and register the cause of the contact. At EoP1, patients will be asked to complete a questionnaire on their preferences (treatment at home or in the outpatient clinic). Moreover, they will be asked to complete the EORTC QLQ-C30, EORTC QLQ-MY20, and FACT Cognitive questionnaires and caregivers will be asked to complete FROM-16 (at home, if necessary). Finally, a joint interview with the patients and their caregivers will be conducted. When all patients have reached EoP1, a focus group interview with involved healthcare professionals at the outpatient clinic will be conducted. For patients continuing elranatamab after EoP1, AEs/SAEs, best obtained response, and duration of response will continuously be monitored until EoP2 according to SoA.

Collaborating researchers and departments

Blandecentralen, Sygehusapotek FYN Odense University Hospital J.B. Winsløwsvej 6C, Entrance 212 C DK-5000 Odense C

• Tina Mose