Study of CLR 131 in Relapsed or Refractory Select B-Cell Malignancies (CLOVER-1)

B-cell malignancies represent a diverse collection of diseases and, taken together, make up
the majority of hematologic malignancies. B-cell lymphomas represent the largest percentage
of these neoplasms, and the relapsed and/or refractory B-cell lymphomas have proven very
difficult to treat. Success rate, defined as complete or partial response, is as low as 2% to
4% in many of these diseases, and they remain an area of a significant unmet medical need.

CLR 131 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, CLR 131 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 B-cell malignancies, the radiosensitivity of these cancers, and initial preclinical and
clinical experience with radioiodinated CLR1404, Cellectar Biosciences has chosen to assess
CLR 131 in a phase 2 trial.

Inclusion Criteria:

All Patients

- Histologically or cytologically confirmed MM; CLL/SLL, LPL, MZL; or MCL OR
histologically proven, DLBCL. Patients with transformed DLBCL are allowed.

- ECOG performance status of 0 to 2

- 18 years of age or older

- Life expectancy of at least 6 months

- Platelets ≥ 100,000/µL (if full-dose anticoagulation therapy is used, platelets ≥
150,000/µL are required)

- WBC count ≥ 3000/µL

- Absolute neutrophil count ≥ 1500/µL

- Hemoglobin ≥ 9 g/dL (last transfusion, if any, must be at least 1 week prior to study
registration, and no transfusions are allowed between registration and dosing)

- Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2

- Alanine aminotransferase < 3 × upper limit of normal (ULN)

- Bilirubin < 1.5 × ULN

- International normalized ratio (INR) < 2.5

- If patient is on full-dose anticoagulation therapy, the anticoagulation therapy must
be reversible and reversal of the anticoagulation therapy must not be
life-threatening, as judged by the Investigator

- Patients who have undergone stem cell transplant must be at least 100 days from
transplant

- Patient is judged by the Investigator to have the initiative and means to be compliant
with the protocol and be within geographical proximity to make the required study
visits

- Patient or his or her legal representative has the ability to read, understand, and
provide written informed consent for the initiation of any study-related procedures

- Female patients of childbearing potential must have a negative pregnancy test within
24 hours of dosing

- Women of childbearing potential and men who are able to father a child must agree to
use an effective method of contraception (eg, oral contraceptives, double-barrier
methods such as a condom and a diaphragm, intrauterine device, Norplant, Depo-Provera)
during the study and for 12 months following administration of the study drug

Patients with Multiple Myeloma

- At least 2 prior regimens, which must include at least 1 approved proteasome inhibitor
(bortezomib, carfilzomib, or ixazomib) and at least 1 approved immunomodulatory agent
(thalidomide, lenalidomide, or pomalidomide), with or without maintenance therapy,
unless patients are intolerable to such agents or ineligible to receive such agents.

- Progressive disease defined by any of the following:

- 25% increase in serum M-protein from the lowest response value during (or after)
last therapy and/or absolute increase in serum M-protein of ≥ 0.5 g/dL

- 25% increase in urine M-protein from the lowest response value during (or after)
last therapy and/or absolute increase in urine M-protein of ≥ 200 mg/24 h

- 25% increase in bone marrow plasma cell percentage from the lowest response value
during (or after) last therapy. Absolute bone marrow plasma cell percentage must
be ≥ 10% unless prior CR when absolute bone marrow plasma cell percentage must be
≥ 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

- Failure to obtain a partial response or better to current treatment, or cannot
further improve their response to current treatment

- Appearance of new extramedullary disease

- Measurable disease defined by any of the following:

- Serum M-protein > 0.5 g/dL

- Urine M-protein > 200 mg/24 h

- Serum FLC assay: Involved FLC level ≥ 10 mg/dL provided serum FLC ratio is
abnormal.

- Measurable plasmacytoma or extramedullary disease

- Patients who are non-secretors will be considered for accrual on a case-by-case basis
by the Sponsor and will require an Investigator plan to define PD prior to enrollment
and to assess clinical benefit after treatment.

Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Lymphoplasmacytic
Lymphoma, or Marginal Zone Lymphoma

- Prior treatment with at least 2 prior regimens, which may include chemotherapy, an
approved anti-CD20 antibody with or without maintenance therapy, and an approved
targeted agent, unless patients are ineligible to receive such agents

- Patients with Helicobacter pylori+ mucosa-associated lymphoid tissue lymphoma must
have received 1 prior antibiotic regimen for H pylori

- At least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable
extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. Additional
parameters (e.g., measurable IgM for patients with Lymphoplasmacytic Lymphoma) may be
allowed if they meet current NCCN guidelines for symptomatic disease. Patients with
uptake by FDG-PET scan may be allowed with prior approval of Sponsor.

Patients with Mantle Cell Lymphoma

- Prior treatment with at least 1 prior regimen

- At least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable
extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. Patients with
uptake by FDG-PET scan may be allowed with prior approval of Sponsor.

Patients with Diffuse Large B-Cell Lymphoma

- Relapsed or refractory to combination chemotherapy for DLBCL that contains rituximab
and an anthracycline; or is intolerable to such agents. Relapsed disease is defined as
either recurrence of disease after a CR or PD after achieving a partial response (PR)
or SD. Refractory disease is defined as failure to achieve at least SD with any 1 line
of therapy or with PD ≤ 3 months of the most recent chemotherapy regimen.

- At least 1 measurable nodal lesion with longest diameter > 15 mm or 1 measurable
extranodal lesion (eg, hepatic nodule) with longest diameter > 10 mm. Patients with
uptake by FDG-PET scan may be allowed with prior approval of Sponsor.

Exclusion Criteria:

- Ongoing Grade 2 or greater toxicities due to previous therapies. Stable, tolerable
Grade 2 AEs (eg, neuropathy) may be allowed.

- Prior external-beam RT resulting in greater than 20% of total bone marrow receiving
greater than 20 Gy.

- Prior total body or hemi-body irradiation. Patients who have received prior low-dose
total body or hemi-body irradiation may be allowed on a case-by-case basis after
discussion with Sponsor (considerations may include factors such as time since
irradiation, total lifetime accumulated dose, etc.)

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

- Central nervous system involvement unless previously treated with surgery or
radiotherapy with the patient neurologically stable and off corticosteroids

- For patients with CLL/SLL, LPL, or MZL, transformation to a more aggressive form of
NHL

- Ongoing chronic immunosuppressive therapy

- Clinically significant bleeding event within prior 6 months

- Ongoing anti-platelet therapy (except low-dose aspirin [eg, 81 mg daily] for
cardioprotection)

- Anti-cancer therapy within two weeks of initial CLR 131 infusion. Low dose
dexamethasone for symptom management is allowed

- Radiation therapy, chemotherapy, immunotherapy, or investigational therapy within 2
weeks of eligibility-defining bone marrow biopsy.

- History of hypersensitivity to iodine

- Any other concomitant serious illness or organ system dysfunction that in the opinion
of the Investigator would either compromise patient safety or interfere with the
evaluation of the safety of the test drug including, but not limited to,
myelodysplastic syndromes; New York Heart Association class III-IV heart disease;
unstable angina pectoris; serious cardiac arrhythmia requiring medication or a
pacemaker/automatic implantable cardioverter defibrillator; myocardial infarction
within the past 6 months; uncontrolled hypertension; severe peripheral vascular
disease; ongoing hemodialysis or peritoneal dialysis; poorly controlled severe chronic
obstructive pulmonary disease; ongoing/active infection requiring antibiotics; and
uncontrolled hypothyroidism or hyperthyroidism

- Major surgery within 6 weeks of enrollment

- Known history of human immunodeficiency virus, hepatitis C, or hepatitis B infection

- Pregnancy or breast-feeding