Study to Assess Adverse Events and Change in Disease Activity of Intravenous (IV) Lemzoparlimab With or Without Oral/IV Dexamethasone and in Combination With Oral/IV/Subcutaneous Anti-Myeloma Regimens in Adult Participants With Multiple Myeloma

Multiple myeloma (MM) accounts for more than 10% of all blood cancers and 1% of all cancers. The purpose of this study is to assess how safe lemzoparlimab is and how lemzoparlimab moves through the body of adult participants with MM when given with or without dexamethasone, and in combination with other anti-myeloma regimens. Adverse events and change in disease activity will be assessed.

Lemzoparlimab is an investigational drug being developed for the treatment of relapsed/refractory (R/R) MM. Study doctors put the participants in groups called treatment arms. Two different dose levels of lemzoparlimab will be explored. Each treatment arm receives a different treatment combination depending on stage of the study and eligibility. This study will include a dose escalation phase to determine the best dose of lemzoparlimab, followed by a dose expansion phase to confirm the dose. Approximately 163 adult participants with R/R MM will be enrolled in the study in approximately 60 sites worldwide.

In the Dose Escalation arms, participants will receive intravenous (IV) lemzoparlimab with or without dexamethasone (oral/IV) in combination with pomalidomide (oral) or carfilzomib (IV) or subcutaneous (SC) daratumumab in 28-day cycles. In the Dose Expansion arms, participants will receive lemzoparlimab (IV) alone or with dexamethasone (oral/IV) in combination with pomalidomide (oral) or carfilzomib (IV) or daratumumab (SC) in 28-day cycles.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests and side effects.


Eligibility Criteria:
Inclusion Criteria:

* Diagnosis of relapsed/refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen based on the investigator's determination of the International Myeloma Working Group (IMWG) criteria.

  * Relapsed defined as previously treated myeloma that progresses and requires initiation of salvage therapy, but does not meet criteria for refractory myeloma.
  * Refractory defined as disease that is nonresponsive (failure to achieve minimal response or development of progressive disease) while on primary or salvage therapy, or progresses within 60 days of last therapy.
* Measurable disease per the protocol within 28 days prior to enrollment.
* Arm A - Lemzoparlimab with or without Dexamethasone

  * For Both Escalation and Expansion Phase, participant must have refractory to 3 prior lines of treatment of anti-myeloma treatments, as outlined in the protocol.
* Arm B - Lemzoparlimab + Pomalidomide-Dexamethasone

  * For Escalation Phase - Participant must have received at least 3 prior lines of therapy, as outlined in the protocol.
  * For Expansion Phase- Participant must have received at least 2 prior line of therapy, as outlined in the protocol.
* Arm C - Lemzoparlimab + Carfilzomib-Dexamethasone

  * For Escalation Phase- Participant must have received at least 3 prior lines of therapy as outlined in the protocol.
  * For Expansion Phase- Participant must have received at least 1 prior line of therapy.
* Arm D - Lemzoparlimab + Daratumumab-Dexamethasone -- For Both Escalation and Expansion Phase - Participant must: --- Have received at least 3 prior lines of therapy, as outlined in the protocol.

Exclusion Criteria:

* Arm B - Lemzoparlimab + Pomalidomide-Dexamethasone

  * For Both Escalation and Expansion Phase participant must have had no prior treatment with pomalidomide.
* Arm C - Lemzoparlimab + Carfilzomib-Dexamethasone

  * For Both Escalation and Expansion Phase - prior treatment with carfilzomib.
* Arm D - Lemzoparlimab + Daratumumab-Dexamethasone

  * For Both Escalation and Expansion Phase - prior treatment with daratumumab or other anti-CD38 therapy.