Safety, Efficacy, and Pharmacokinetics of Continuous Subcutaneous Lenalidomide in Multiple Myeloma (MM)

Inclusion Criteria:

1. Male or female ≥18 years at the time of informed consent.

2. Autologous stem cell transplant (ASCT) ineligible.

3. SARS -CoV2 virus (COVID)-19 negative.

4. A prior diagnosis of MM as defined by International Myeloma Working Group (IMWG)criteria (Appendix 7).

5. Documented measurable disease following first line therapy defined as:

• Serum monoclonal protein ≥1.0 g/dL by protein electrophoresis.

• ≥200 mg/24 hours of monoclonal protein in the urine on 24-hour electrophoresis.

• Serum free light chain (SFLC) ≥10 mg/dL AND abnormal serum kappa to lambda freelight chain (FLC) ratio.

6. Intended to be treated in 2nd line or greater with lenalidomide, dexamethasone, anda PI.

7. Proteasome inhibitor sensitive defined as progression free for > 6 months fromcessation of PI or never received a prior PI.

8. Progression per IMWG criteria on the most recent line of therapy.

9. Eastern Cooperative Oncology Group (ECOG-Appendix 1) performance status ≤2 (patientswith a performance status of 3 based solely on bone pain secondary to MM may beeligible following consultation and approval by the Medical Monitor).

10. Willing to comply with the protocol defined Lenalidomide Pregnancy Risk MinimizationPlan for the prevention of pregnancy (Appendix 5). Females of childbearing potential (FCBP) must have a medically supervised negative serum or urine pregnancy test 4-14days prior to planned start of treatment and again 24 hours prior to initiation ofstudy medication. All FCBP must agree to either commit to continued abstinence fromsexual intercourse or begin TWO acceptable methods of birth control AT THE SAMETIME, at least 28 days before receiving the first dose of STAR-LLD. FCBP must alsoagree to ongoing pregnancy testing. Males must agree to use a latex or syntheticcondom during sexual contact with a FCBP from the time of starting study treatmentthrough 28 days after the last dose, even if they have had a vasectomy.

11. Able to take anti-thrombotic prophylaxis.

12. The following laboratory results must be met during screening:

• ANC ≥1,000 cells/mm3 (1.0 x 109/L).

• Platelet count ≥75,000 cells/mm3 (75 x 109/L).

• Hemoglobin ≥8.0 g/dL (red blood cell (RBC) transfusions are permitted prior toinitiation of study drug if hemoglobin is stable for 72 hours).

• Total bilirubin ≤1.5 x upper limit of normal (ULN), or patient diagnosed withGilberts syndrome with a total bilirubin <5.0 x ULN that has been reviewed andapproved by the Medical Monitor.

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 x ULN.

• Calculated creatinine clearance ≥60 mL/min. Appendix 4

• Negative pregnancy test for FCBP (must be obtained within 4-14 days before theinitiation of study drug.

13. The following criteria must be met within 72 hours prior to first administration ofcontinuous infusion STAR-LLD:

• ANC ≥1,000 cells/mm3 (1.0 x 109/L).

• Platelet count ≥75,000 cells/mm3 (75 x 109/L).

• Hemoglobin ≥8.0 g/dL (RBC transfusions are permitted prior to initiation ofstudy drug if hemoglobin is stable for 72 hours).

• Calculated creatinine clearance ≥60 mL/min. Appendix 4

• Negative pregnancy test for FCBP (must be obtained within 24 hours of firstdose of study drug).

14. Able and willing to receive percutaneous ambulatory therapy.

15. Has an in-home care partner willing to receive training from a nurse for assistancewith pump management.

Exclusion Criteria:

1. Pregnant or breastfeeding.

2. Received an ASCT.

3. Venous thromboembolism within 12 months of starting treatment on study.

4. Patients with active hepatitis B or C or human immunodeficiency virus (HIV) positiveand on active therapy for those viral illnesses.

5. Currently taking any investigational therapy for the treatment of MM. A 28-daywashout prior to Cycle 1 Day 1 is required for any previous investigational therapy.

6. Received a prior treatment line containing lenalidomide and failed to achieve anobjective response (CR, VGPR or PR).

7. Discontinued a prior line of treatment due to intolerability to lenalidomide.

8. Concomitant use of strong CYP3A inducers (seehttps://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers#table3-3).

9. Concurrent clinically significant amyloidosis or plasma cell leukemia or POEMSsyndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy,monoclonal protein and skin changes).

10. Known active infection requiring systemic anti-infective treatment (prophylactictreatment is permitted).

11. Prior malignancies within the previous 3 years, other than previously treatedsquamous and basal cell carcinomas of the skin and carcinoma in situ of the cervixor breast or another malignancy that is considered cured with minimal risk ofrecurrence (e.g., very low and low risk prostate cancer in active surveillance).

12. Prior major surgical procedure or radiation therapy within 4 weeks of the initiationof STAR-LLD (this does not include limited course of radiation used for managementof bone pain within 7 days of initiation of STAR-LLD).

13. Any other condition that precludes adequate understanding, cooperation, andcompliance with study procedures or any condition that could pose a risk to thepatient's safety, as per the Investigator's judgment.