Study of Benralizumab in People With Skin Side Effects Caused by Cancer Therapies

Inclusion criteria

• Patients must have pathologically or cytologically confirmed solid or hematologic cancers.

OR

• Patient is receiving alpelisib for PIK3CA-Related Overgrowth Spectrum disorder.
• Female and male aged 18 to 85 years, inclusively, at the time of Week 0/Day 1 of treatment.
• Patients must have a therapy-related CTCAE grade 2/3 (See Appendix A)cutaneous adverse event defined as any cutaneous reaction listed below and blood eosinophil counts of at least .3 K/mcl.

• Rash maculo-papular
• Bullous dermatitis
• Pruritus
• Urticaria
• Eczema
• Patients must plan to continue on culprit drugs (cancer patients).
• Patients planning to receive alpelisib indicated for PIK3CA-Related Overgrowth

Spectrum disorder OR patients receiving immunotherapy and/or targeted therapy, including but not limited to the following agents, will be eligible for inclusion:

• Immunotherapies: ipilimumab, nivolumab, pembrolizumab, avelumab, durvalumab, atezolizumab tremelimumab.
• Targeted therapies: trastuzumab, pertuzumab, alpelisib, osimertinib, everolimus, temsirolimus, sorafenib, regorafenib.

• Patients using topicals/orals for indication of skin rash/pruritus for at least 7 days should continue using these drugs for the study duration
• Adequate bone marrow, liver and renal function:
• Total bilirubin ≤ 1.5 x the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver involvement of their cancer)
• Serum creatinine ≤ 1.8 xULN or calculated creatinine clearance >45 ml/min
• Platelet count > 50 K/mcL , hemoglobin (Hb) > 8 g/dL, absolute neutrophil count (ANC) >1.0 K/mcL. Blood transfusion to meet the inclusion criteria will not be allowed.

• ECOG performance status 0-1 (see Appendix C).
• Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.
• Female patients are authorized to participate if they meet the following criteria:
• Women of child bearing potential must meet both of the following conditions:
• Have a negative serum pregnancy test prior to enrollment and within 14 days prior to administration of the investigational product (IP).
• Patient must use an effective form of birth control (confirmed by the Investigator) throughout the study duration and within 16 weeks after last dose of IP.
• Female subjects who cannot bear children as evidenced by one or more of the following:
• Bilateral Oophorectomy
• Bilateral Salpingectomy
• Bilateral Salpingectomy-Oophorectomy
• Hysterectomy
• Menopause (no menses ≥ 1 year prior to treatment)
• Surgical Sterilization (i.e., tubal ligation or blockage) Note: If criteria not met, patient should be regarded as having child bearing potential

• Subject must be able to receive a subcutaneous injection.
• New/worsening ercAE within 90 days prior to study enrollment. Note: This assessment will be performed by the treating investigator.

Exclusion criteria

• Concurrent use of another investigational drug or device for the ercAE (i.e., outside of study treatment) during, or within 4 weeks of treatment.
• Patients receiving prednisone ≥ 20mg a day.
• Known use of anti-IL-5 agents or biologics for the treatment of asthma which are known to decrease blood eosinophil levels.
• Patients cannot use new topicals or medications for indication of pruritus or skin rash
• Known history of anaphylaxis to biologic therapy.
• A helminthic parasitic infection diagnosed within 24 weeks prior to the first treatment, that had not been treated with, or has failed to respond to, standard of care therapy.
• Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy.
• Active infection that would impair the ability of the patient to receive study treatment.
• Women who are pregnant or breast-feeding.
• Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation.
• Receipt of live attenuated vaccines 30 days prior to the date of randomization

° Receipt of inactive/killed vaccinations (e.g., inactive influenza) is allowed provided they were not administered within 1 week before/after any investigational product administration.

• Known history of allergy or reaction to the investigational product formulation