A Study of Melflufen-dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide

This is a randomized, controlled, open-label, Phase 3 multicenter study which will enroll
patients with RRMM following 2-4 lines of prior therapy and who are refractory to
lenalidomide in the last line of therapy as demonstrated by disease progression on or within
60 days of completion of the last dose of lenalidomide.

Patients will be randomized to either one of two arms:

Arm A: Melflufen 40 mg on Day 1 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each
28-day cycle.

Arm B: Pomalidomide 4 mg daily on Days 1 to 21 and dexamethasone 40 mg on Days 1, 8, 15 and
22 of each 28-day cycle.

Patients ≥ 75 years of age will have a reduced dose of dexamethasone of 20 mg on Days 1, 8,
15 and 22 for both Arm A and Arm B.

Patients may receive treatment until such time as there is documented disease progression,
unacceptable toxicity or the patient/treating physician determines it is not in the patient's
best interest to continue.

Dose modifications and delays in therapy may be implemented based on patient tolerability as
detailed in the protocol. In the event of a cycle delay, unrelated to dexamethasone toxicity,
it is recommended to continue dexamethasone weekly.

Inclusion Criteria:

1. Male or female, age 18 years or older

2. A prior diagnosis of multiple myeloma with documented disease progression requiring
further treatment at time of screening

3. Measurable disease defined as any of the following:

- Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis.

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

- Serum free light chain ≥ 10 mg/dL AND abnormal serum kappa to lambda free light
chain ratio

4. Received 2-4 prior lines of therapy, including lenalidomide and a PI, either
sequential or in the same line, and is refractory (relapsed and refractory or
refractory) to both the last line of therapy and to lenalidomide (≥ 10 mg)
administered within 18 months prior to randomization. Refractory to lenalidomide is
defined as progression while on lenalidomide therapy or within 60 days of last dose,
following at least 2 cycles of lenalidomide with at least 14 doses of lenalidomide per
cycle.

5. Life expectancy of ≥ 6 months

6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

7. Females of child bearing potential (FCBP) must have a negative serum or urine
pregnancy test prior to start of treatment. Participants must agree to ongoing
pregnancy testing. All patients must be willing to comply with all requirements of the
USA pomalidomide Risk Evaluation and Mitigation Strategy (REMS) program or the
pomalidomide Pregnancy Prevention Plan (PPP).

8. Ability to understand the purpose and risks of the study and provide signed and dated
informed consent.

9. 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula
(QTcF) interval of ≤ 470 msec Fridericia Formula.

10. The following laboratory results must be met during screening and also immediately
before study drug administration on Cycle 1 Day 1:

- Absolute neutrophil count (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

- Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), or patients diagnosed with
Gilberts syndrome, that have been reviewed and approved by the medical monitor.

- Aspartate transaminase (AST /SGOT) and alanine transaminase (ALT/SGPT) ≤ 3.0 x
ULN.

- Renal function: Estimated creatinine clearance by Cockcroft-Gault formula ≥ 45
mL/min.

11. Must be able to take antithrombotic prophylaxis.

12. Must have, or be willing to have an acceptable central catheter. (Port a cath,
peripherally inserted central catheter [PICC-line], or central venous catheter)
(Insertion only required if randomized to Arm A).

Exclusion Criteria:

1. Primary refractory disease (i.e. never responded (≥ MR) to any prior therapy)

2. Evidence of mucosal or internal bleeding or platelet transfusion refractory

3. Any medical conditions that, in the Investigator's opinion, would impose excessive
risk to the patient or would adversely affect his/her participating in this study.

4. Prior exposure to pomalidomide

5. Known intolerance to IMiDs.

6. Known active infection requiring parenteral or oral anti-infective treatment within 14
days of randomization.

7. Other malignancy diagnosed or requiring treatment within the past 3 years with the
exception of adequately treated basal cell carcinoma, squamous cell skin cancer,
carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in
active surveillance.

8. Pregnant or breast-feeding females

9. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or
confuse compliance or follow-up evaluation

10. Known human immunodeficiency virus or active hepatitis C viral infection

11. Active hepatitis B viral infection (defined as HBsAg+).

- Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-,
Anti-HBs+, Anti-HBc-).

- Non-active hepatitis B (HBsAg-, Anti-HBs+, Anti-HBc+) may be enrolled at the
discretion of the investigator after consideration of risk of reactivation.

12. Concurrent symptomatic amyloidosis or plasma cell leukemia

13. POEMS syndrome

14. Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple
myeloma within 3 weeks (6 weeks for nitrosoureas) prior to randomization. IMiDs, PIs
and or corticosteroids within 2 weeks prior to randomization. Other investigational
therapies and monoclonal antibodies within 4 weeks of randomization. Prednisone up to
but no more than 10 mg orally q.d. or its equivalent for symptom management of
comorbid conditions is permitted but dose should be stable for at least 7 days prior
to randomization

15. Residual side effects to previous therapy > grade 1 prior to randomization (Alopecia
any grade and/or neuropathy grade 2 without pain are permitted)

16. Prior peripheral stem cell transplant within 12 weeks of randomization

17. Prior allogeneic stem cell transplantation with active graft-versus-host-disease.

18. Prior major surgical procedure or radiation therapy within 4 weeks of the
randomization

19. Known intolerance to steroid therapy