CTO-IUSCCC-0854

This is a pilot single arm, non-randomized study involving adult patients with melanoma receiving standard of care treatment for non-resectable or metastatic disease with ferritin levels below 30 ng/ml and transferrin saturations of less than 20%.

Cancer-associated anemia remains an underestimated and inadequately treated chronic condition that adversely affects the quality of life and overall prognosis in cancer patients. The correction of anemia in cancer patients would be a clinically applicable strategy to prevent and/or mitigate the expansion of tumor promoting erythroid progenitor cells (EPCs). Iron is an essential functional component of erythrocyte hemoglobin and is a crucial regulator of erythropoiesis. Strategies to therapeutically target the immunosuppressive machinery have emerged as a promising approach for cancer treatment. By promoting EPCs differentiation/maturation in anemic melanoma patients, immunosuppression could be mitigated and the therapeutic activity of immune checkpoint inhibitors enhanced.

A dose of intravenous iron will be given one week prior to standard of care chemotherapy and antibodies CD71 and CD235a will be used to detect EPCs in circulation and tumor microenvironment.

Inclusion Criteria:

1. ≥ 18 years old adults at the time of informed consent
2. Ability to provide written informed consent and HIPAA authorization
3. Unresectable or metastatic Melanoma
4. Eligible for standard of care treatment
5. ECOG performance status 0-2
6. Anemia defined as hemoglobin \< 13 g/dl in addition to ferritin \< 100 ng/ml and/or transferrin saturation \< 30%

Exclusion Criteria:

1. History of anaphylactic reaction to intravenous iron or any proposed standard of care treatments
2. Diagnosis of hemoglobinopathies
3. Therapeutic Iron supplementation in the past 3 months (oral iron as part of MVI allowed)
4. Diagnosis of hemochromatosis
5. Symptomatic brain metastases that require local treatment (brain metastasis which will be treated with systemic immunotherapy or treated metastasis with without need for steroids for symptomatic management are eligible).
6. Pregnant or lactating female adults
7. Active infections which in research teams' opinion increases risk for toxicities
8. Any condition that in the opinion of PI may interfere with patient being able to complete the required procedures.

Melanoma, Skin

Indiana University (IU)

• Indiana University Hospital / IU Simon Cancer Center