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

Phase II Study of IL-5-receptor-alpha-chain (IL-5Rα) Inhibition With Benralizumab for Eosinophil-Related Cutaneous Adverse Events in Cancer Patients

The purpose of this study is to find out whether the study drug benralizumab is a safe treatment that can reduce the skin side effects caused by cancer treatment by reducing the level of eosinophils in your blood. Reducing the skin side effects of your cancer treatment may improve quality of life and allow participants to continue to receive their usual cancer treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumor; Hematologic Malignancy; Solid Tumor, Adult; Solid Carcinoma
• Intervention / Treatment: Drug: Benralizumab

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alina Markova, MD; Phone Number: 646-608-2342; Email: markovaa@mskcc.org
• Study Contact Backup: Name: Mario E. Lacouture, MD; Phone Number: 646-608-2337; Email: LacoutuM@mskcc.org

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Cancer Center
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center @ Suffolk - Commack (Limited Protocol Activities)
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • Hauppauge, New York, United States, 11788
      • Memorial Sloan Kettering Cancer Center Suffolk - Hauppauge (Limited Protocol Activities)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with eosinophil-related cutaneous events; Study participants will have grade 2/3 eosinophil-related cutaneous adverse events	Drug: Benralizumab; All eligible patients will receive a benralizumab dose of 30 mg SC administered by a healthcare provider once every 4 weeks for the first 3 doses, followed by once every 8 weeks for 3 additional doses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent reduction in CTCAE grade 2/3 eosinophil-related cutaneous adverse events	To evaluate the percent reduction in CTCAE grade 2/3 eosinophil-related cutaneous adverse events to grade ≤1 resulting from checkpoint inhibitors (CPIs) or targeted therapies with absolute blood eosinophil counts of at least .3 K/mcl.	4 weeks

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Mario E. Lacouture, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2020
• Primary Completion (Estimated): March 16, 2024
• Study Completion (Estimated): March 16, 2024

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 17, 2020

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Benralizumab; Memorial Sloan Kettering Cancer Center; hematologic cancer; solid cancer; 20-344
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: 20-344

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No