Dose Escalation Study of I-131-CLR1404 in Patients With Relapsed or Refractory Multiple Myeloma

Multiple myeloma (MM) is an incurable, monoclonal proliferation of plasma cells.
Approximately 80,000 Americans are affected by MM with approximately 22,000 new cases
diagnosed and 11,000 deaths each year. The introduction of newer therapies in the past twenty
years, such as autologous stem cell transplantation and novel agents such as proteasome
inhibitors and immune modulating drugs has improved outcomes, with current median overall
survival estimates of 3-10 years depending on a number of patient-, disease- and
treatment-related factors. However, despite these innovations, myeloma relapse is inevitable.
Therefore, there is a clear need for improved therapies for MM and, in particular, for
relapsed disease.

I-131-CLR1404 is a radioiodinated therapeutic that exploits the selective uptake and
retention of phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel
cancer-targeted small-molecule compound (CLR1404) is radiolabeled with the isotope iodine-131
(I-131). Radioiodinated CLR1404 has been evaluated in over 60 xenograft and spontaneous
(transgenic) tumor models. In all but two cases of hepatocellular carcinoma, CLR1404
demonstrated selective cancer cell uptake and retention. In various rodent tumor models,
I-131-CLR1404 has also demonstrated tumor growth delay and prolongation of survival.

Based on the critical unmet medical need for effective agents with novel mechanisms of action
in MM, the exquisite radiosensitivity of MM, and initial preclinical and clinical experience
with radioiodinated CLR1404, Cellectar Biosciences has chosen to assess I-131-CLR1404 in a
MM-specific phase 1 trial.

Inclusion Criteria:

- Histologically or cytologically confirmed multiple myeloma

- Prior treatment with or intolerance to proteasome inhibitor and immunomodulator

- Bone marrow biopsy within 28 days of study drug infusion demonstrating at least 5%
plasma cell involvement

- Progressive disease defined by any of following:

25% increase in serum M-protein from lowest response value during (or after) last
therapy and/or absolute increase in serum M-protein of > or equal to 0.5 g/dL; 25%
increase in urine M-protein from lowest response value during (or after) last therapy
and/or absolute increase in urine M-protein of > or equal to 200 mg/24h; 25% increase
in bone marrow plasma cell percentage from lowest response value during (or after)
last therapy - absolute bone marrow plasma cell percentage must be > or equal to 10%
unless prior complete response when absolute bone marrow plasma cell percentage must
be > or equal to 5%; 25% increase in serum FLC level from the lowest response value
during (or after) last therapy - the absolute increase must be > 10 mg/dL; new onset
hypercalcemia > 11.5 mg/dL

- Measurable disease defined by any of following: Serum M-protein > 1 g/dL; Urine
M-protein > 200 mg/24h; Serum free light chain (FLC) assay: involved FLC level > or
equal to 10 mg/dL provided serum FLC ratio is abnormal; subjects who are non-secretors
will be considered on a case-by-case basis

- Eastern Cooperative Oncology Group performance status of 0 to 2

- Life expectancy of at least 6 months

- Have initiative and means to be compliant with protocol and within geographical
proximity to make required study visits as judged by Investigator

- Subject or legal representative has ability to read, understand and provide written
informed consent for study related procedures

- Women of childbearing potential must have negative pregnancy test within 24 hours of
enrollment

- Women of childbearing potential and men who are able to father a child, must agree to
use an effective contraception method during study and for 12 months following study
drug administration

Exclusion Criteria:

- Grade 2 or greater toxicities due to previous therapies, subject to laboratory
abnormalities listed below. Stable, tolerable Grade 2 adverse events may be allowed at
discretion of Investigator

- Prior external beam radiation therapy resulting in greater than 20% total bone marrow
receiving greater than 20 Gy

- Prior radioisotope therapy

- Prior total body or hemi-body irradiation

- Extradural tumor in contact with the spinal cord or tumor located where swelling in
response to therapy may impinge upon spinal cord

- Subject has any of following laboratory abnormalities: WBC < 3000/uL; ANC < 1500/uL;
Hemoglobin < 8 g/dL; Estimated glomerular filtration rate < 30 mL/min/1.73 m2; ALT > 3
x ULN ; Bilirubin > 1.5 x ULN

- Platelet count < 100,000/uL without full-dose anticogulation therapy

- Platelet count < 150,000/uL with ongoing full-dose anticoagulation therapy

- Clinically significant bleeding event, as judged by investigator, within prior 6
months

- Chronic immunosuppressive therapy

- Anti-platelet therapy, except low-dose aspirin for cardioprotection

- PTT > 1.3 x ULN

- INR > 1.3

- Radiation therapy, chemotherapy, immunotherapy, investigational therapy or
corticosteroid use within 2 weeks of or after eligibility-defining bone marrow biopsy.
Bisphosphonates and denosumab are permitted if subject has been receiving for at least
90 days

- History of hypersensitivity to iodine

- Any other concomitant serious illness or organ system dysfunction in opinion of
Investigator would either compromise subject safety or interfere with test drug safety
evaluation

- Major surgery within 6 weeks of enrollment

- Known history of HIV, hepatitis C or hepatitis B infection

- Pregnancy or breast-feeding