Phase II Study of IL-5-receptor-alpha-chain (IL-5Rα) Inhibition With Benralizumab for Eosinophil-Related Cutaneous Adverse Events in Cancer Patients
Phase: PHASE2
Conditions: Solid Tumor, Solid Carcinoma, Solid Tumor, Adult, Hematologic Malignancy
Sponsor: Memorial Sloan Kettering Cancer Center

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
 
MSK PROTOCOL COVER SHEET 
Phase II Study of IL-5-receptor-alpha-chain (IL-5Ra) Inhibition With Benralizumab for 
Eosinophil-Related Cutaneous Adverse Events in Cancer Patients 
Principal Investigator/Department: Alina Markova/Medicine 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
Table of Contents 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA ......................................................................... 3 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS .................................................................................. 3 
3.0 
BACKGROUND AND RATIONALE ........................................................................................ 4 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION............................................................... 10 
4.1 
Design ............................................................................................................................... 10 
4.2 
Intervention ........................................................................................................................ 10 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS & NON-THERAPEUTIC ASSESSMENTS ............ 10 
6.0 
CRITERIA FOR PARTICIPANT ELIGIBILITY ....................................................................... 11 
6.1 
Participant Inclusion Criteria .............................................................................................. 11 
6.2 
Participant Exclusion Criteria ............................................................................................. 12 
7.0 
RECRUITMENT PLAN ......................................................................................................... 13 
7.1 
Research Participant Registration ...................................................................................... 13 
7.2 
Randomization................................................................................................................... 14 
8.0 
INFORMED CONSENT PROCEDURES ................................................................................ 14 
9.0 
PRE-TREATMENT/INTERVENTION ..................................................................................... 14 
10.0 TREATMENT/INTERVENTION PLAN .................................................................................. 15 
11.0 EVALUATION DURING TREATMENT/INTERVENTION ...................................................... 17 
12.0 CRITERIA FOR REMOVAL FROM STUDY .......................................................................... 19 
13.0 
CRITERIA FOR OUTCOME ASSESSMENT AND ENDPOINT EVALUABILITY .................. 19 
14.0 BIOSTATISTICS ................................................................................................................... 19 
15.0 TOXICITIES/RISKS/SIDE EFFECTS .................................................................................... 23 
15.1 Serious Adverse Event (SAE) Reporting ............................................................................ 25 
15.2 External AE Reporting ....................................................................................................... 25 
16.0 PROTECTION OF HUMAN PARTICIPANTS ........................................................................ 28 
16.1 Privacy .............................................................................................................................. 28 
16.2 Data Management ............................................................................................................... 29 
16.3 Quality Assurance ............................................................................................................. 29 
16.4 Data and Safety Monitoring ............................................................................................... 29 
17.0 
REFERENCES ..................................................................................................................... 30 
18.0 
APPENDICES ...................................................................................................................... 36 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
This is a single-center, single-arm phase II study to evaluate the efficacy and safety of the 
anti-IL-5Rα chimeric monoclonal antibody benralizumab for the treatment of eosinophil- 
related cutaneous adverse events (ercAEs) resulting from immunotherapies or targeted 
therapies. Forty eight (48) patients will be enrolled and the estimated time to completion is 2 
years. The primary endpoint for the study is the percent reduction in CTCAE grade 2/3 
eosinophil-related cutaneous adverse events to grade ≤1. Eosinophil-related cutaneous 
adverse events are defined as maculopapular rash, pruritus/urticaria, bullous pemphigoid, or 
DRESS syndrome that are associated with blood eosinophil counts of at least .3 K/mcl. 
Secondary endpoints are safety and tolerability of benralizumab, calculated rash body 
surface area (BSA), relative dose intensity (RDI) of anticancer therapy, measurement of 
patient-reported quality of life, the ability to continue anticancer agents, effects on 
corticosteroid naïve and dependent/refractory ercAEs, the need for additional supportive care 
interventions (i.e. corticosteroids, antihistamines), and reduction in blood and skin 
eosinophils. An exploratory endpoint is analyzing eosinophils and Th2 immune pathway 
blood biomarkers ( IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, 
tryptase) that correlate with benralizumab efficacy. Patients with a diagnosis of solid or 
hematologic cancers undergoing treatment with checkpoint inhibitors (CPIs) or targeted 
therapies with a grade 2/3 cutaneous adverse associated with blood eosinophil counts of at 
least .3 K/mcl will be treated with benralizumab 30mg once every 4 weeks for the first 3 
doses (Week 0/Day 1, Week 4/Day 28, and Week 8/Day 56), followed by once every 8 weeks 
for 3 additional doses (Week 16/Day 112, Week 24/Day 168, and Week 32/Day 224). CTCAE 
v5.0 ercAE assessments will be done at baseline and then at Week 2/Day14, Week 4/Day 
28, and Week 8/Day 56, Week 16/Day 112, Week 24/Day 168, Week 32/Day 224 and 4 
weeks post-last dose. Patients may remain on study until ercAE progression or unacceptable 
toxicity from benralizumab for up to 32 weeks. 
 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS 
Primary Objectives 
• 
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. 
 
Secondary objectives 
• 
To investigate changes in adverse event-related quality of life using patient-reported 
questionnaires (PRO-CTCAE, Skindex 16). 
• 
To investigate the safety/tolerability of benralizumab in patients with eosinophil- 
related cutaneous adverse events. 
• 
To investigate the need for supportive medications (corticosteroids, antihistamines, 
immunosuppressants) in patients treated with benralizumab. 
• 
To investigate the effect of benralizumab on subsequent planned cycles of checkpoint 
inhibitors (CPIs), or targeted therapies. 
• 
To compare the effect of benralizumab on corticosteroid naïve and corticosteroid 
dependent/refractory ercAEs. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
• 
To correlate the percent reduction in blood absolute eosinophil numbers and skin 
histology with clinical response to benralizumab. 
• 
To investigate change in body surface area (BSA) of ercAE to quantify change in 
affected area in response to benralizumab over time. 
• 
To investigate relative dose intensity (RDI) and compliance of patients’ culprit 
anticancer therapy for the duration of the trial. 
Exploratory objectives 
• 
To discover changes in blood biomarkers (IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL- 
10, IL-12p70, IL-13, TNF-α, tryptase) that correlate with response to benralizumab. 
 
3.0 
BACKGROUND AND RATIONALE 
 
Background on eosinophil related cutaneous adverse events 
 
In areas where helminth exposure is uncommon, medication‐related drug reactions are a 
common cause of peripheral and blood eosinophilia (Ramirez and Frias, British Pharmacol 
Soc 2017). In the absence of systemic involvement, this condition generally constitutes a 
drug effect that can be caused by a myriad of medication classes, such as penicillin and 
sulphonamide drugs, and resolves upon drug discontinuation (Khoury and Bochner, JACIP 
2018). In the oncology setting, eosinophil-related cutaneous adverse events (ercAEs) are 
also frequent (10-20%) (Fischer et al, Am J Dermatopathol 2015; Lucas-Truyols et al, Acta 
Dermosiligrof 2017; Fujisawa et al, J Dermatol Sci 2017), but their impact is greater: they 
result in interruption or discontinuation of life-prolonging antineoplastic agents, negatively 
affect a patient’s quality of life, may affect other organs (i.e. liver and kidneys as part of the 
Drug Rash with Eosinophilia and Systemic Symptoms (Cho et al, Int J Mol Sci 2017)), and 
usually require treatment with corticosteroids which carry their own set of toxicities in an 
already vulnerable patient population. Indeed, in oncology drug development trials, 
dermatologic toxicities are a dose-limiting toxicity in 2.4% of cases (Drilon et al, Cancer 
2016). There are no FDA approved therapies for ercAEs, and whereas off-label use of 
corticosteroids and interruption of the offending agent may be effective in most patients, there 
are no additional therapeutic options for patients with corticosteroid dependent/refractory 
ercAEs. 
 
 
Possible eosinophil effects 
in cutaneous adverse 
events. 
• Damage of tissues by 
cytotoxic granule proteins 
• Antibody-dependent cellular 
cytotoxicity 
• Activation of tissue 
remodeling and fibrosis 
• Antigen presentation 
• Modulation of the adaptive 
immune response 
• Promotion of B cell 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
responses 
• Induction of tissue repair processes 
 
Abundant clinical data suggests that eosinophils play a pivotal role in cancer and cutaneous 
reactions to anticancer therapies (Davis and Rothemberg, Cancer Immunol Res 2014; 
Tracey et al, Am J Dermatopathol 2017; Sakkal and Miller, Curr Med Chem 2016; Roufousse 
2015; Blank et al, Eur J Pharmacol 2016)). Indeed, between 1/1/2015 and 3/11/2019 there 
were 2652 patients evaluated by the dermatology service at MSKCC with skin conditions and 
associated eosinophilia (MEL, unpublished data). Of these, 584 patients were receiving 
immunotherapies, and the remaining were receiving other drugs including cytotoxic 
chemotherapy, targeted therapies, or supportive care drugs. Therefore, eosinophils represent 
an attractive target for the treatment of immune—related adverse events (irAEs), as they 
have been reported in biopsy samples from skin, gut, and lungs in patients treated with 
immune checkpoint inhibitors (CPIs) developing rash, colitis, and pneumonitisin the majority 
of patients with drug reactions (Kizawa et al, J Clin Oncol 2019; Occhipinti et al, Drug Saf 
Case 2018; Furubayashi et al, Mol Clin Oncol. 2019; Georgianos et al, Case Rep Nephrol 
2019). In an analysis of 267 inpatients with ercAEs by any type of drug, 16.5% resulted in 
oncology patients, with 8.6% harboring an active cancer diagnosis, and the culprit being an 
antineoplastic agent in 11 of 154 drugs (7.1%) (Ramirez et al, Br J Clin Pharmacol 2017). In 
addition, high eosinophil and eosinophil-related cytokines (eotaxin-1, IL-9, TARC, IL-4) in 
blood have been associated with irAEs in melanoma patients treated with immune checkpoint 
inhibitors (ICIs) (Fujisawa et al, J Dermatol Sci 2017). Eosinophils are also well-known 
mediators of severe drug reactions in the non-cancer population, most notably 
maculopapular rashes (Kardaun et al, Br J Dermatol 2007). These are classified as Type 4 
(Gell and Coombs) reactions and the immune mediators are Th2 cells and IL-4/13 and IL-5, 
with eosinophils playing a major role (Ramirez et al, Biomed Res Int 2018). 
 
Many of these reactions involve only the skin but some patients manifest systemic features 
including fever, eosinophilia, lymphadenopathy and organ dysfunction which may principally 
affect the liver, bone marrow and/or kidneys (Cho et al, Int J Mol Sci 2017). The combination 
of a widespread eruption with systemic dysfunction is termed DRESS (Drug Reaction with 
Eosinophilia and Systemic Symptoms) or DIHS (Drug-Induced Hypersensitivity Syndrome). 
Eosinophilia is part of the RegiSCAR diagnostic criteria for Drug Reaction with Eosinophilia 
and Systemic Symptoms (DRESS/DIHS). There is now the realization that patients with 
DRESS often develop a worsening of the clinical picture after the initial reaction starts 
resolving. There may be recurrence of fever, either a leukocytosis or lymphopenia and 
deterioration of organ function. This is due to reactivation of members of the herpes virus 
family, HHV6 and HHV7 in particular, but EBV and/or CMV as well. Higher eosinophil counts 
correlated with poor liver function, extended hospitalization, and prolonged corticosteroid use 
in patients with EM–type, urticaria-like, and morbilliform drug eruptions. In addition, CPI lead 
to eosinophil-mediated cutaneous irAE that impact QoL and ability of patients to receive life 
prolonging or saving therapies (Phillips et al, J Clin Oncol 2019). 
In a broad evaluation of non-cancer inpatient adverse cutaneous drug reactions, only 18% 
had peripheral eosinophilia (>300 × 106 cells l−1). Eosinophil related cutaneous adverse 
events (ercAEs) have been described as a type IVb reaction, which involves a Th2‐mediated 
immune response with secretion of IL‐4, IL‐13, and IL‐5. IL‐5 is known to be the key factor in 
regulating the growth, differentiation, and activation of eosinophils. Eosinophil activity is also 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
augmented by Th1 cytokines, including IL‐3 and granulocyte‐macrophage colony‐stimulating 
factor (GM‐CSF). There are numerous types of ercAE, ranging from benign, asymptomatic 
eosinophilia to potentially fatal reactions resulting in organ damage, such as drug reaction 
with eosinophilia and systemic symptoms (DRESS). The extent of clinical involvement is also 
heterogeneous, ranging from isolated peripheral eosinophilia or single organ involvement 
(lung, kidney, liver) with skin being the most common, to systemic disease affecting multiple 
organs, classically exemplified by drug reaction with eosinophilia and systemic symptoms 
(DRESS). Previous in vivo and in vitro data indicate that eosinophils are particularly involved 
in patients with DRESS syndrome. DRESS is a distinctive reaction, first described during 
treatment with anticonvulsant drugs (most commonly carbamazepine), and subsequently with 
a multitude of medication classes. However, antiepileptic medications remain the 
predominant cause of DRESS, with an incidence of 1 per 5000 to 10,000 exposures. 
 
The actual definition of DRESS was proposed by Bocquet et al. in 1996 and updated in 2007 
by the Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) Study Group. DRESS 
syndrome diagnosis is complex due to the wide variety of signs and symptoms not all present 
at the same time in the patient. The phenotype of the skin is imprecise; the most common 
presentation is polymorphous maculopapular (85%); however, monomorphic (15%), pustules 
(30%), and purpura (26%) also occur. Hypereosinophilia was present in 95% of cases. Other 
haematological manifestations were atypical lymphocytes (67%) and lymphadenopathy 
(54%). Internal organ involvement has been reported in 91% of cases, primarily due to 
hepatic injury (elevation of liver function tests or hepatomegaly). Other frequent symptoms 
were high fever (90%) and mild mucosal involvement (56%). The pathogenesis is unclear, 
but is most likely to involve several aspects, including a network of drug metabolites, specific 
HLA alleles, herpes viruses (EBV, HHV‐6, HHV‐7, or CMV), and immune system activation. 
Patients with high peripheral blood eosinophilia had poorer liver function, prolongation of 
hospitalization, and higher cumulative doses of corticosteroids. Eosinophil count in patients 
with an erythema multiforme‐type drug eruption was associated with severe disease. In the 
RegiSCAR scoring system for the diagnosis of DRESS, the score increases with the degree 
of eosinophilia from one point if eosinophilia is between 700 and 1499 × 106 cells l−1, to two 
points if eosinophilia is >1500 × 106 cells l−1. The spectrum of eosinophilic drug reactions and 
the classes of medication associated with peripheral eosinophilia are expanding. Half (53.3%, 
64/120 cases) of symptomatic eosinophilic drug reactions are potential DRESS cases, with 
higher numbers of cases during hospitalization than in the community. Higher eosinophil 
counts in patients with DRESS are significantly associated with greater impairment of liver 
function, prolonged hospitalization, and higher cumulative doses of corticosteroids. 
 
In absence of other systemic involvement, isolated peripheral blood eosinophilia is a benign 
drug effect that can be caused by a myriad of medication classes. It might be a direct 
physiologic effect of certain cytokine or immune therapies (PD 1/L1 inhibitors, IL2, GM‐CSF) 
secondary to expansion of IL‐5‐producing T cells; however, the mechanisms underlying most 
instances of drug‐related eosinophilia have not been elucidated. Asymptomatic eosinophilia 
by drugs is more frequently observed than symptomatic eosinophilia. Among symptomatic 
eosinophilia cases, the most frequent cause was DRESS (64 cases, 53%), followed by 
eosinophilia with only dermatological symptoms (36 cases, 30%), and then with visceral 
involvement (19 cases, 16%). Substantial tissue damage is unlikely to occur with a low 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
eosinophil count, and expert opinion supports that isolated eosinophilia must be monitored; 
withdrawal of any drug that is not crucial for the patient is recommended, which is 
problematic in the oncology setting. Drug‐induced eosinophilia, however, frequently prompts 
clinical concern regarding impending organ involvement. Data have shown that the 
development of symptoms after eosinophilia onset was more likely with earlier onset of 
eosinophilia, higher eosinophil count, and a delayed onset of corticosteroids. In a prospective 
cohort study of 824 patients receiving prolonged intravenous antibiotic therapy as 
outpatients, patients with eosinophilia had a significantly higher likelihood of rash (adjusted 
HR, 4.16; 95% CI: 2.54–6.83) or renal injury (HR, 2.13; 95% CI: 1.36–3.33), compared with 
the patients without eosinophilia. However, DRESS syndrome only occurred in seven 
patients (Blumenthal et al, JACI 2015). Data support that DRESS syndrome can occur at a 
higher frequency than previously reported in the drug‐induced eosinophilia literature. 
 
Targeting ercAEs with benralizumab would represent a paradigm shift, as adverse events 
would be amenable to prophylactic (if very frequent or in populations at risk) and effective 
reactive therapies, precluding the need for immunotherapy dose interruptions or 
discontinuations, while maintaining quality of life and efficacy. There is precedent for this 
concept, as the tumor necrosis α (TNF) inhibitor infliximab is recommended for the treatment 
of ICI-related colitis and the IL-6 inhibitor tocilizumab has been approved for the treatment of 
cytokine release syndrome related to chimeric antigen receptor T (CAR-T) therapies in 
cancer (Buder-Bakhaya et al, Front Immunol 2018). At MSKCC we have reported the efficacy 
of agents targeting IL12/23, IL4/13, CD20, and IgE in patients treated with cutaneous AEs 
related to immunotherapies, which has allowed continued administration of the culprit 
medication (Phillips et al, J Clin Oncol 2019). 
Benralizumab 
 
Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody (IgG1, 
kappa) indicated for the add-on maintenance treatment of patients with severe asthma aged 
12 years and older, and with an eosinophilic phenotype. Besides linking IL-5Rα through its 
Fab regions, benralizumab also binds via the constant Fc fragment to the FcγRIIIa receptor, 
located on cell membrane of natural killer (NK) cells. In this regard, it is worth noting that 
benralizumab was developed in Chinese hamster ovary cells not expressing the α-1,6- 
fucosyltransferase enzyme. As a consequence, 
lack of the fucose molecule in the sugar 
component of the CH2 domain of the constant 
segment of the monoclonal antibody is responsible 
for a remarkable enhancement (5 to 50 times) of 
benralizumab affinity for the FcγRIIIa receptor of 
NK cells. In particular, with regard to the original 
fucosylated antibody, afucosylation makes 
benralizumab capable of inducing a ≥1000-fold 
amplification of the apoptotic mechanism named 
antibody-dependent cell-mediated cytotoxicity 
(ADCC). Indeed, benralizumab is a potent inducer 
of eosinophil apoptosis operated by NK cells 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
through the release of the proapoptotic proteins perforin and granzyme B. Afucosylation- 
dependent ADCC has also been demonstrated by benralizumab-induced increase in 
eosinophil staining with annexin V, a well-known biomarker of apoptosis. 
 
It can thus be argued that benralizumab is capable of killing eosinophils via a dual 
mechanism: the blockade of IL-5-mediated survival of these cells and the enhancement of 
eosinophil apoptosis induced by activation of the FcγRIIIa receptor of NK cells. By acting via 
such very powerful modalities, benralizumab rapidly and effectively depletes eosinophils in 
patients with asthma, thereby drastically reducing cell counts in both airways and peripheral 
blood. Benralizumab was recently approved by US FDA for the add-on biological therapy of 
severe eosinophilic asthma. A meta-analysis referring to 1951 subjects with eosinophilic 
asthma, enrolled in several different phase 1, 2, and 3 randomized controlled trials, 
demonstrated that, when compared to placebo, benralizumab induced significant score 
improvements of asthma control questionnaire-6 (ACQ-6) and asthma quality of life 
questionnaire (AQLQ) and enhanced Forced expiratory volume (FEV1)and also decreased 
the annual rate of disease exacerbations. 
 
In the 52-week Phase 2 dose-ranging trial, asthma patients received 1 of 3 doses of 
benralizumab [2 mg (n=81), 20 mg (n=81), or 100 mg (n=222)] or placebo (n=222). All doses 
were administered every 4 weeks for the first 3 doses, followed by every 8 weeks thereafter. 
Median blood eosinophil levels at baseline were 310, 280, 190 cells/μL in the 2, 20, and 100 
mg benralizumab and placebo groups, respectively. Dose-dependent reductions in blood 
eosinophils were observed. At the time of the last dose (Week 40), median blood eosinophil 
counts were 100, 50, 40, 170 cells/μL in the 2, 20, and 100 mg benralizumab and placebo 
groups, respectively. 
 
A reduction in blood eosinophil counts was observed 24 hours post dosing in a Phase 2 trial. 
In Trials 1 and 2, following subcutaneous (SC) administration of benralizumab at the 
recommended dose blood eosinophils were reduced to a median absolute blood eosinophil 
count of 0 cells/μL. This magnitude of reduction was seen at the first observed time point, 4 
weeks of treatment, and was maintained throughout the treatment period. 
 
Treatment with benralizumab was also associated with reductions in blood basophils, which 
was consistently observed across all clinical studies. In the Phase 2 dose-ranging trial, blood 
basophil counts were measured by flow cytometry. Median blood basophil counts were 45, 
52, 46, and 40 cells/µL in the 2 mg, 20 mg and 100 mg benralizumab and placebo groups, 
respectively. At 52 weeks (12 weeks after the last dose), median blood basophil counts were 
42, 18, 17, and 46 cells/µL in the 2 mg, 20 mg and 100 mg benralizumab and placebo 
groups, respectively. 
 
Benralizumab and placebo induced similar patterns of adverse effects. Benralizumab was 
characterized by a good safety profile. In fact, only mild-to-moderate and self-limiting adverse 
reactions occurred, such as cough, bronchitis, fever, headache, muscle spasms, dizziness, 
hyperhidrosis, and anxiety. After 12 weeks of treatment, anti-benralizumab antibodies were 
found in 6 patients, but no clinical consequence was reported. In 18 patients with severe 
eosinophilic and corticosteroid-dependent asthma showed that 30 mg of benralizumab, 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
administered subcutaneously every 4 or 8 weeks, when compared to placebo, significantly 
decreased the counts of mature eosinophils in both blood and induced sputum. In blood, 
benralizumab also significantly reduced the number of eosinophil progenitors. A similar result 
was also detected in induced sputum, where, however, this effect of benralizumab did not 
reach the threshold of statistical significance, probably because of the small number of 
matched data sets. Moreover, in blood, benralizumab significantly lowered the number of 
ILC2 cells expressing IL-5Rα, and a similar effect was also observed in induced sputum, 
where, however, only a trend, and not a significant difference, was found. Serum eosinophil 
derived neurotoxins (EDN) concentrations were also significantly diminished by 
benralizumab. In addition, benralizumab significantly increased the levels of granzyme B and 
interferon-γ in cell-free sputum supernatants. Therefore, the latter findings suggest that 
benralizumab was able to stimulate the activity of NK cells. All these biological effects of 
benralizumab were paralleled by relevant clinical and functional improvements, including a 
decrease in the maintenance dosage of oral corticosteroids, a better asthma control, and an 
increased ratio of prebronchodilator FEV1 to FVC (forced vital capacity). In particular, 
because of its very effective action as IL-5Rα antagonist, benralizumab has been shown to 
be capable of significantly inhibiting eosinophil differentiation in the bone marrow, as well as 
eosinophilic infiltration of airways. These eosinopenic effects are further potentiated by 
ADCC-mediated eosinophil apoptosis, operated by NK cells, and stimulated by 
benralizumab. At clinical and functional levels, such a dual mechanism of action of 
benralizumab translates into relevant improvements, including a significant decrease of 
asthma exacerbations, a better symptom control, a marked sparing effect on the intake of 
oral corticosteroids, and an important attenuation of airflow limitation. All these features, 
associated with a very good safety and tolerability profile, make benralizumab a valuable 
therapeutic option for add-on biological treatment of severe eosinophilic asthma. These 
effects were associated with drastic reductions in blood eosinophil counts and also in serum 
concentrations of the eosinophilic cytotoxic proteins ECP and EDN. Benralizumab is currently 
being investigated for other indications in which eosinophils play a major role, such as atopic 
dermatitis, eosinophilic gastritis, esophagitis, polyposis, rhinosinusitis, granulomatosis with 
polyangiitis, and hypereosinophilic syndrome. Based on the implication of eosinophils in 
cancer therapy-related cutaneous events, there is a strong rationale for its use in this setting. 
Interestingly, a 71 year old patient treated with the PD-L1 inhibitor pembrolizumab and 
worsening asthma associated with eosinophilia was treated with benralizumab. In 2 days 
there was resolution of asthma attacks and cough, and peak flow increased, along with a 
marked reduction in eosinophils, and tumor response to pembrolizumab was maintained 
(Izumo et al, 2019) 
 
PIK3CA-Related Overgrowth Spectrum disorder 
 
On April 5, 2022, the Food and Drug Administration granted accelerated approval to alpelisib 
for adult and pediatric patients two years of age and older with severe manifestations of 
PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy. 
 
In a retrospective study, approximately 50% of metastatic breast cancer patients receiving 
alpelisib develop dermatologic adverse events with associated peripheral eosinophilia (Wang 
et al, 2020). 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
Based on this new FDA-approved indication for alpelisib and the high incidence rate of 
alpelisib dermatologic adverse events with associated peripheral eosinophilia, benralizumab 
may provide benefit for this non-cancer patient population. 
 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
4.1 
Design 
This is a single-arm phase II study of patients with grade 2/3 eosinophil-related cutaneous 
adverse events treated with benralizumab. The primary objective is to determine the 
reduction of 2/3 ercAEs to grade ≤1. Secondary endpoints are reduction in blood and skin 
eosinophils and its association with response, safety/tolerability of benralizumab, impact on 
quality of life, concomitant supportive medications, calculated rash body surface area (BSA), 
relative dose intensity (RDI) of anticancer therapy, and ability to continue anticancer therapy. 
An exploratory endpoint is analyzing blood biomarkers that correlate with benralizumab 
efficacy. 
 
4.2 
Intervention 
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. This is the approved dose and schedule for eosinophilic asthma. 
Eosinophil-related cutaneous AE assessments will be conducted at baseline, Week 0/Day 1 
(+/-3), Week 2/Day 14 (+/-3), Week 4/Day 28 (+/-3 ), and Week 8/Day 56 (+/-3) using CTCAE 
v5.0. Patients may remain on study until progression of ercAE or unacceptable toxicity from 
benralizumab. Patients will continue receiving the investigational agent for up to 32 weeks (6 
doses). 
 
 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS & NON-THERAPEUTIC ASSESSMENTS 
 
Benralizumab is a humanized recombinant monoclonal antibody of the isotype IgG1k 
immunoglobulin that specifically binds to the alpha chain of the interleukin 5 receptor (IL-5R) 
with a dissociation constant of 11 pM. The IL-5 receptor is expressed on the surface of 
eosinophils and basophils. Benralizumab inhibits the binding of IL-5 as well as the hetero- 
oligomerization of the alpha and beta subunits of the IL-5R, thus blocking, signal 
transduction. In an in vitro setting, the absence of fucose in the Fc domain of benralizumab 
facilitates binding (45.5 nM) to FcɣRIII receptors on immune effectors cells, such as natural 
killer (NK) cells, leading to apoptosis of eosinophils and basophils through antibody- 
dependent cell-mediated cytotoxicity (ADCC). 
 
Benralizumab is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow 
solution for subcutaneous injection. Since benralizumab is a protein, a few translucent or 
white to off-white particles may be present in the solution. The protein chemical formula is 
C6492H10060N1724O2028S42; with a protein average weight of 146054.0 Da. Benralizumab should 
be administered by a healthcare professional. In line with clinical practice, monitoring of 
patients after administration of biologic agents is recommended. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
Benralizumab, FDA approved on November 14, 2017, was developed by MedImmune, 
AstraZeneca's global biologic research and development arm. Benralizumab is provided as a 
30 mg/mL solution in a single-dose prefilled syringe, provided by AstraZeneca 
Pharmaceuticals LP (NDC Code(s): 0310-1730-30, 0310-1730-85). Each single-dose 
prefilled syringe delivers 1 mL containing 30 mg benralizumab, L-histidine (1.4 mg); L- 
histidine hydrochloride monohydrate (2.3 mg); polysorbate 20 (0.06 mg); α,α-trehalose 
dihydrate (95 mg); and Water for Injection, USP. The single-dose prefilled syringe contains a 
1 mL glass syringe with a staked 29 gauge ½ inch stainless steel needle. It needs to be 
refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. 
 
6.0 
CRITERIA FOR PARTICIPANT ELIGIBILITY 
6.1 
Participant 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. 
o Rash maculo-papular 
o Bullous dermatitis 
o Pruritus 
o Urticaria 
o 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: 
o Immunotherapies: ipilimumab, nivolumab, pembrolizumab, avelumab, 
durvalumab, atezolizumab tremelimumab. 
o 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: 
o Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) 
o Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x 
ULN (≤ 5 x ULN for subjects with liver involvement of their cancer) 
o Alkaline phosphatase ≤ 2.5 x ULN (≤ 5 x ULN for subjects with liver 
involvement of their cancer) 
o Serum creatinine ≤ 1.8 xULN or calculated creatinine clearance >45 ml/min 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
o 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: 
o 
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. 
o 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. 
 
6.2 
Participant 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. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
• 
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 
o 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 
 
7.0 
RECRUITMENT PLAN 
Potential research subjects will be identified by a member of the patient’s treatment team, the 
protocol investigator, or research team. Patient recruitment most likely will occur in the 
medical oncology and dermatology clinics. If the investigator is a member of the treatment 
team, s/he will screen their patients’ medical records for suitable research study participants 
and discuss the study and their potential for enrolling in the research study. Potential subjects 
contacted by their treating physician will be referred to the investigator/research staff of the 
study. Investigators will discuss the study and review/sign the informed consent documents 
with the patient. 
 
The principal investigator may also screen the medical records of patients with whom they do 
not have a treatment relationship for the limited purpose of identifying patients who would be 
eligible to enroll in the study and to record appropriate contact information in order to 
approach these patients regarding the possibility of enrolling in the study. 
 
During the initial conversation between the investigator/research staff and the patient, the 
patient may be asked to provide certain health information that is necessary to the 
recruitment and enrollment process. The investigator/research staff may also review portions 
of their medical records in order to further assess eligibility. They will use the information 
provided by the patient and/or medical record to confirm that the patient is eligible and to 
contact the patient regarding study enrollment. If the patient turns out to be ineligible for the 
research study, the research staff will destroy all information collected on the patient during 
the initial conversation and medical records review, except for any information that must 
be maintained for screening log purposes. 
 
In most cases, the initial contact with the prospective subject will be conducted either by the 
treatment team, investigator or the research staff working in consultation with the treatment 
team. The recruitment process outlined presents no more than minimal risk to the privacy of 
the patients who are screened and minimal PHI will be maintained as part of a screening log. 
For these reasons, we seek a (partial) limited waiver of authorization for the purposes of (1) 
reviewing medical records to identify potential research subjects and obtain information 
relevant to the enrollment process; (2) conversing with patients regarding possible 
enrollment; (3) handling of PHI contained within those records and provided by the potential 
subjects; and (4) maintaining information in a screening log of patients approached (if 
applicable). 
 
7.1 
Research Participant Registration 
 
Confirm eligibility as defined in the section entitled Inclusion/Exclusion Criteria. Obtain 
informed consent, by following procedures defined in section entitled Informed Consent 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
Procedures. During the registration process registering individuals will be required to 
complete a protocol specific Eligibility Checklist. The individual signing the Eligibility Checklist 
is confirming whether the participant is eligible to enroll in the study. Study staff are 
responsible for ensuring that all institutional requirements necessary to enroll a participant to 
the study have been completed. See related Clinical Research Policy and Procedure #401 
(Protocol Participant Registration). 
 
7.2 
Randomization 
Not applicable 
8.0 
INFORMED CONSENT PROCEDURES 
Before protocol-specified procedures are carried out, consenting professionals will explain full 
details of the protocol and study procedures as well as the risks involved to participants prior 
to their inclusion in the study. Participants will also be informed that they are free to withdraw 
from the study at any time. All participants must sign an IRB/PB-approved consent form 
indicating their consent to participate. This consent form meets the requirements of the Code 
of Federal Regulations and the Institutional Review Board/Privacy Board of this Center. The 
consent form will include the following: 
 
1. The nature and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies.) 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information. In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 
 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
9.0 
PRE-TREATMENT/INTERVENTION 
The following assessments need to be preformed within the below timelines: 
 
Within 45 days of treatment start: 
• 
Signed Informed Consent Form 
 
Within 30 days of treatment start: 
• 
Skin biopsy per SOC 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
 
Prior to registration and within 14 days of treatment start: 
• 
Serum pregnancy test for women of child-bearing potential 
 
On day -7 to -1: 
• 
Medical history 
• 
Demographics 
• 
Physical Examination and vital signs, including heart rate, blood pressure, weight, and 
temperature 
• 
Skin exam 
• 
Concomitant medication review 
• 
ECOG performance status 
• 
CBC with differential 
• 
Comprehensive Metabolic Panel, including Albumin, alkaline phosphatase, total 
bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, potassium, total 
protein, SGOT[AST], SGPT[ALT], sodium 
• 
Phosphorus 
 
 
10.0 TREATMENT/INTERVENTION PLAN 
• 
Benralizumab 30mg as a subcutaneous injection will be administered by a healthcare 
professional at once every 4 weeks for the first 3 doses (Week 0/Day 1, Week 4/Day 
28, and Week 8/Day 56), followed by once every 8 weeks for 3 additional doses 
(Week 16/Day 112, Week 24/Day 168, and Week 32/Day 224), per the labeling 
instructions. 
 
 
 
 
• 
Patients will also have a comprehensive physical examination at Week 0/Day 1 
• 
Skin examination prior to benralizumab administration will be completed at Week 
0/Day 1, Week 4/Day 28, Week 8/Day 56). 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
• 
Phlebotomy for CBC w differential at every visit (Screening, Week 0/Day 1, Week 
2/Day 14, Week 4/Day 28, Week 8/Day 56, Week 16/Day 112, Week 24/Day 168, 
Week 32/Day 224, and 4 Weeks post-last dose). 
• 
Total body photography at Screening, Week 0/Day 1, Week 4/Day 28, Week 8/Day 
56,. 
• 
Research blood collection for biomarker analysis (MSD Panel and IL-5) on Week 
0/Day 1, Week 4/Day 28 and Week 8/Day 56: 
o Approximately 10 mL of blood will be collected in a green top sodium heparin 
Vacutainer tube. This sample will be sent to the Immune Monitoring Facility 
(IMF). 
o Approximately 4 mL of blood will be collected in a lavender top tube (with 
EDTA). This sample will be sent to Mayo Clinic. 
 
Missed doses will not be made up. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
11.0 EVALUATION DURING TREATMENT/INTERVENTION 
 
Study Procedures 
Screening 
Visit 
(-7 days to 
Day 1 )5 
Week 0/ 
Day 1 
Week 2/ Day 
14 
(+/- 3 days) 
Week 4/ 
Day 28 
(+/- 3 days) 
Week 8/ 
Day 56 
(+/- 3 days) 
Week 16/ 
Day 112 (+/- 
7 days)4 
Week 24/ 
Day 168 (+/- 
7 days)4 
Week 32/ 
Day 224 (+/- 
7 days)4 
4 Weeks post-last 
dose 
(+/- 7 days) 
Informed Consent 
X1 
Demographics 
X 
Medical history 
X 
Concomitant medication review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum pregnancy test, per SOC 
and if applicable 
X2 
Skin biopsy3 
X 
X 
CBC with differential 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Comprehensive Metabolic Panel 
X 
Physical exam and vital signs (HR, 
BP, weight, and temperature) 
X 
Skin Exam (prior to Benralizumab 
administration) 
X 
X 
X 
ECOG Performance Status 
(Appendix C) 
X 
Total body photography 
X 
X 
X 
X 
Eosinophil-related Adverse Event 
Grading (CTCAE v5.0) (Appendix A) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Research blood collection for 
biomarker analysis (IL-5 & MSD 
Panel) 
X 
X 
X 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
 
Adverse event evaluation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patient self-assessment (PRO- 
CTCAE (Appendix D) & Skindex 16 
(Appendix B) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
RegiSCAR Scoring System for 
Diagnosing DRESS Syndrome 
X 
Benralizumab 30mg SC 
administration 
X 
X 
X 
X 
X 
X 
SOC, standard of care. 
1. Informed consent within 45 days prior to treatment. 
2. Serum pregnancy test for WOCBP within 14 days prior to treatment. 
3. The baseline skin biopsy will be obtained within 30 days of treatment start, if applicable per standard of care. The biopsy at day 
28 will be RNB if the patient’s symptoms are improving. 
4. Assessments will continue as long as the patient continues receiving benralizumab (up to 32 weeks). If a patient discontinues 
benralizumab, they will move to the 4 weeks post-last dose follow-up visit. 
5. Screening and Week 0/Day 1 visits can be combined as long as comprehensive metabolic panel, CBC w/ differential, and 
pregnancy test (if applicable) are resulted to confirm eligibility prior to first benralizumab injection. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
12.0 CRITERIA FOR REMOVAL FROM STUDY 
• 
Patients may be removed from the study for protocol non-compliance with visits. 
• 
If at any time the patient develops unacceptable toxicity he/she will be removed from 
study. 
• 
Participants can be removed from the study at any time if the investigator considers 
that it is in their best interest to do so. 
• 
Patients may withdraw consent from the study at any time. 
13.0 
CRITERIA FOR OUTCOME ASSESSMENT AND ENDPOINT EVALUABILITY 
Please refer to Section 11.0 regarding the timing of ercAE assessments. Documentation 
(photographic) must be provided for patients removed from study for ercAE progression. 
Response and ercAE severity will be evaluated in this study using the Common Terminology 
Criteria for Adverse Events version 5.0. Changes in severity grade by specific 
skin/subcutaneous tissue AE term will be used. 
 
13.1 Criteria for Therapeutic Response/Outcome Assessment 
Evaluation of ercAE by CTCAE v5.0 
Response (R): Grade 2 or 3 event reduction to grade 0 or 1. 
Nonresponding AE (nrAE): Grade 2 or 3 event that does not reduce to grade 0 or 1. 
Progressive AE (pAE): Grade 2 event that increases by ≥1 grade in severity. 
 
13.2 Criteria for Study Endpoint Evaluability 
Patients who are removed from the study prior to starting Benralizumab will be considered 
inevaluable and replaced. Patients who receive at least one dose of Benralizumab will be 
included in the evaluation of the primary objective if they have a post-therapy documented 
clinical response. Patients who progress and are placed on agents instead of or in addition to 
the culprit agents will be removed from the study. Patients who receive steroids at doses 
greater than prednisone 20mg a day or equivalent or other immunosuppressive agents to 
manage additional irAEs will be considered a failure for the primary endpoint. 
14.0 BIOSTATISTICS 
This is a single-center single-arm phase II study to evaluate the efficacy and safety of 
benralizumab for the treatment of eosinophil-related cutaneous adverse events (ercAE) in 
patients having grade 2/3 ercAE to various treatments (such as checkpoint inhibitors 
ortargeted therapies) with blood eosinophil counts of at least .3 K/mcL. 
The primary endpoint of efficacy is defined as the proportion of patients who have a reduction 
from CTCAE grade 2/3 eosinophil-related cutaneous adverse events to grade ≤1 following 
treatment with benralizumab. The study will be declared positive if ≥70% of patients have a 
reduction of grade 2/3 eosinophil-related cutaneous adverse events to grade ≤1 (between 
Week 0/Day 1 and Week 4/Day 28). 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
Data from medical oncology and other MSK visits will be collected at the last study visit for 
each patient and immune related adverse events with grade and attribution will be included in 
the final analysis. 
Data analysis will be conducted by externally funded biostatistician (consultant), George 
Dranitsaris of Augmentium Pharma Consulting Inc. The Consultant will serve to review, 
analyze, and assess data, documents and information provided from MSK, which shall be 
MSK’s Confidential Information, and provide subsequent guidance in a format. The 
Consultant will also provide independent information to support MSK’s clinical research 
activities. Additional projects that are beyond the scope of this WP with require a separate 
document executed in writing between the Parties. The Services shall be provided by 
Consultant at the direction and discretion of MSK and all deliverables or other materials 
produced by the Consultant shall be subject to Section 5 of the Agreement. The consultant 
will have access to participant PHI including name, demographics (DOB, age, gender, race, 
ethnicity), medical history (treatment start and end date and treatment information) and 
questionnaire responses. Details of this contract are available on the PIMS regulatory binder. 
14.1 Populations for Analyses 
A total of 48 evaluable patients will be accrued to this study. Patients having a solid tumor or 
hematologic malignancy, grade 2/3 ercAE to various treatments and blood eosinophil counts 
of at least .3 K/mcL will be recruited from the medical oncology and dermatology clinics 
(Section 7.0). Patients will receive benralizumab treatment on Week 0/Day 1 and Week 
4/Day 28, and will be assessed for efficacy at baseline Week 0/Day 1 (+/- 3 days), Week 
2/Day 14 (+/- 3 day), Week 4/Day 28 (+/- 3day) and Week 8/Day 56 (+/- 3 days) (Section 
4.2). If the second dose is missed, it will not be made up (Section 10.0). Patients can remain 
on study until progression of ercAE or unacceptable toxicity related to benralizumab up to 32 
weeks (Section 4.2). 
Patients will be considered evaluable as long as they receive at least one dose of 
benralizumab. Patients who are enrolled and removed from study before they receive their 
first dose of benralizumab will be considered inevaluable and will be replaced. Data analyses 
for the primary, secondary and exploratory endpoints will be based on 28 evaluable patients. 
Summary statistics will also be reported separately for patients removed from the study, 
including a summary of reasons for removal, their median duration in the study and range, 
mean and standard deviation of their eosinophil counts, and proportion of in ercAE 
categories at baseline and at all follow-up times prior to their removal from the study. 
 
Primary endpoint: 
Efficacy: We will compare the decrease in patients with grade 2/3 ercAEs to grade ≤1 
(between Week 0/Day 1 and Week 4/Day 28) in 28 evaluable patients using a one-sample 
test for proportions. Benralizumab will be declared to be efficacious if a response (reduction 
from grade 2/3 to grade ≤1) is achieved by >70% of patients. As noted in Section 3, high 
eosinophil levels refers to a count of > 300 eosinophils per microliter of blood (based on 
studies in eosinophilic asthma patients that resulted in the approval of benralizumab). With 
an expected response rate of >70% at Week 4/Day 28 and 28 evaluable patients and a 
historical reference value of 40% (response based on an improvement of ercAEs grades of 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
other treatment regimens from clinical experience of the PI) we have >80% power to detect a 
significant difference if we observe a decrease in grade 2/3 ercAEs to grade ≤1 in 17 or more 
of the 28 participants at Week 4/Day 28 based on a mixed model for repeated measures 
analysis with an alpha-level of 5%. An expansion cohort of 19 patients was added once the 
initial 28 patients were accrued. 
 
On average, we expect to accrue 2 patients to this protocol per month. The overall accrual 
period for this study will be 15 months. 
 
Secondary endpoints: 
AE-related quality of life: Quality of life will be assessed for all patients at Week 0/ Day 1, 
Week 2/Day 14, Week 4/Day 28 and Week 8/Day 56, Week 16/Day 112, Week 24/Day 168, 
Week 32/Day 224 and 4 weeks post-last dose using PRO-CTCAE and Skindex 16 (Appendix 
D). Prior to conducting analyses, we will evaluate questionnaire compliance. The amount of 
missing data across the PRO instruments will be summarized. A questionnaire will be 
considered complete if enough questions were completed to be a valid score. Since these 
instruments are broken into sections, completion of any section for a given adverse event will 
be considered complete information for that adverse event. Baseline characteristics of study 
participants with completed and incomplete QOL data will be compared in a descriptive 
manner. Mouth/throat sores, dry skin and itchy skin are reported on a 5-point scale, while 
rash, hives and sensitivity of the skin to sunlight are reported on a 2-point scale. These 
symptoms will be summarized using descriptive statistics. The proportion of patients with 
different levels of these symptoms will be assessed at each study time point along with exact 
binomial confidence intervals. A summary score for the Skindex-16 will calculated for each 
participant at each time point. The total Skindex-16 score will with summarized for each study 
time point along with 95% confidence intervals. 
 
The Skindex-16 has been shown to have good reproducibility (r = 0.88-0.90). Patients 
answer every question with a number ranging from 0 (never bothered) to 6 (always 
bothered). After the questionnaire is completed, the responses to each item are transformed 
to a linear scale of 100 that ranges from 0 (never bothered) to 100 (always bothered). 
Consequently, each item has a minimum score of 0 and a maximum score of 100. The 
Skindex-16 results are reported as an overall score and as 3 domain scores: symptoms, 
emotions, and functioning. For the overall score, the mean score of all items is calculated. 
Thus, the overall score has a minimum of 0 and a maximum of 100. Items 1 through 4 on the 
Skindex-16 pertain to the symptoms domain. The mean of these items is calculated, and a 
symptoms domain score is determined that also ranges from 0 to 100. Similarly, the emotions 
domain is based on items 5 through 11, and an emotions domain score is calculated on a 
scale from 0 to 100. The functioning domain is based on items 12 through 16, and a 
functioning domain score is calculated in the same manner. Skindex-16 items also are 
analyzed within each domain to assess the influence of specific items on the overall domain 
score. The means of the transformed scores for each item are compared statistically within 
each domain. When up to 25% of Skindex-16 items have missing responses, the items with 
non-missing responses will be scored. For the analysis of the Skindex-16 score change from 
baseline, patients with a missing score at week 4 will have the Skindex-16 score imputed by 
their baseline Skindex-16 score. This method is considered conservative under the 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
assumption that the majority of patients will withdraw prematurely from the study, resulting in 
missing the week 4 score. 
 
For the PRO-CTCAE, each item is scored individually, as they are rated 0-4 by the patient. 
Interpretation of scores will be descriptive. If an individual item is not completed, it will be 
considered missing. There are otherwise no subscales or minimum thresholds for item 
completion to calculate a score on a given item. 
 
Safety and tolerability of benralizumab: This endpoint will be measured in terms of CTCAE 
v5.0 ercAE. The proportion of patients with different grade categories (0, 1, 2 etc) will be 
assessed at each study time point along with exact binomial confidence intervals. Patients 
progressing to grade 4 ercAE will be removed from the study (Section 12.0). The proportion 
of such patients at each time point will be reported. The proportion of patients having a 
reduction and the proportion having an increase in ercAE grade category will be reported. 
 
Need for supportive medication: The proportion of patients requiring supportive medications 
such as corticosteroids, antihistamines and immunosuppressants will be reported at each 
time point along with exact binomial confidence intervals. 
 
Effect of benralizumab on subsequent planned cycles of checkpoint inhibitors (CPIs) or 
targeted therapies: We will measure changes in blood eosinophil levels between baseline 
and cycles of various planned treatments for these patients, and report the mean, standard 
deviation, range and number of patients scheduled to receive different therapies. 
 
Effect of benralizumab on corticosteroid naïve and corticosteroid dependent/refractory 
ercAEs: Corticosteroid naïve patients are those not receiving corticosteroids for 14 days 
since Week 0/Day 1 of benralizumab treatment. Corticosteroid dependent/refractory ercAEs 
are patients that are on prednisone 10mg a day or greater at the initiation of study. We will 
report the number of corticosteroid naïve and dependent/refractory ercAE patients, measure 
change in blood eosinophil levels between Week 0/Day 1 and Week 8/Day 56, report 
descriptive statistics such as mean, standard deviation and range in these groups of patients. 
 
Effect on eosinophil counts: Changes in eosinophil counts will be calculated and reported as 
percent reduction +/- standard deviation. In addition to comparing baseline and end-of-study 
percent change in eosinophils, we will also compare percent changes across baseline ercAE 
categories and end-of-study ercAE categories. We will use regression models to examine the 
association between longitudinal measurements of percent change in eosinophils at Week 
0/Day 1, Week 2/Day 14, Week 4/Day 28, and Week 8/Day 56, Week 16/Day 112, Week 
24/Day 168, Week 32/Day 224 and 4 weeks post-last dose and longitudinal measurements 
of ercAE categories. 
 
Body Surface Area (BSA): Changes in BSA of ercAE will be calculated from total body 
photography images taken at Week 0/Day 1, Week 4/Day 28, and Week 8/Day 56. We will 
use regression models and descriptive statistics to quantify change in affected BSA in 
response to benralizumab. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
Relative Dose Intensity (RDI): RDI of the culprit anticancer therapy will be calculated from 
Week 0/ Day 1 to end of study date of the trial for each patient. Relative dosage and 
standard dosage will be derived based on the investigators’ and primary oncologists’ notes 
and other documentation from the electronic medical records at Memorial Sloan Kettering 
Cancer Center. We will use regression models to assess differences in compliance to 
different culprit anticancer therapies in response to benralizumab. 
 
Exploratory objective: 
We will measure blood biomarkers – IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, 
IL-13, TNF-α, tryptase – at Week 0/Day 1, Week 4/Day 28, and Week 8/Day 56. We will 
correlate baseline levels of each biomarker with response to benralizumab, where response 
will be coded as a binary value for each patient with response = 1 if a patient’s ercAE 
reduced to grade 0 or 1, and response = 0 otherwise. We will report the difference in average 
value of biomarkers between the two response groups and the standard error of the 
difference. Next, we will correlate the response with biomarker measurements taken on 
Week 4/Day 28. We will also calculate the slope of each biomarker value over time for each 
patient and correlate the slope with the response. These are exploratory investigation, for 
which we will report differences in means and standard errors, but not p-values. Where 
relevant, we will also report these correlations separately based on the evaluable patients 
and those removed from the study. 
 
15.0 TOXICITIES/RISKS/SIDE EFFECTS 
The dose of benralizumab is 30mg SC once every 4 weeks for the first 3 doses, followed by 
once every 8 weeks for 3 additional doses.. Doses will be delayed for clinically significant 
hematologic and non-hematologic toxicities that are related to protocol therapy according to 
the guidelines described in sections below. Dose adjustments for hematologic toxicity are 
based on the blood counts obtained prior to the day of treatment. 
 
Most common adverse reactions (incidence greater than or equal to 5%) include headache 
and pharyngitis. Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) 
have occurred following administration of benralizumab. These reactions generally occur 
within hours of administration, but in some instances have a delayed onset (i.e., days). In the 
event of a hypersensitivity reaction, benralizumab should be discontinued. 
 
Systemic or topical corticosteroids should not be abruptly interrupted or discontinued upon 
initiation of therapy with benralizumab. Reductions in corticosteroid dose, if appropriate, 
should be gradual. Reduction in corticosteroid dose may be associated with systemic 
withdrawal symptoms and/or unmask conditions previously suppressed by systemic 
corticosteroid therapy. Eosinophils may be involved in the immunological response to some 
helminth infections. Patients with known helminth infections were excluded from participation 
in clinical trials. It is unknown if benralizumab will influence a patient’s response against 
helminth infections. 
 
Treat patients with pre-existing helminth infections before initiating therapy with 
benralizumab. If patients become infected while receiving treatment with benralizumab and 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
do not respond to anti-helminth treatment, discontinue treatment with benralizumab until 
infection resolves. 
 
Across Trials 1, 2, and 3, 1,808 patients received at least 1 dose of benralizumab. The data 
described below reflect exposure to benralizumab in 1,663 patients, including 1,556 exposed 
for at least 24 weeks and 1,387 exposed for at least 48 weeks. The safety exposure for 
benralizumab is derived from two phase 3 placebo-controlled studies (Trials 1 and 2) from 48 
weeks duration [benralizumab every 4 weeks (n = 841), every 4 weeks for 3 doses, then 
every 8 weeks (n = 822), and placebo (n = 847)]. While a dosing regimen of benralizumab 
every 4 weeks was included in clinical trials, benralizumab administered every 4 weeks for 3 
doses, then every 8 weeks thereafter is the recommended dose. The population studied was 
12 to 75 years of age, of which 64% were female and 79% were white. 
 
Adverse reactions that occurred at greater than or equal to 3% incidence are shown below. 
 
Adverse Reactions with BENRALIZUMAB with Greater than or Equal to 3% Incidence 
in Patients with Asthma (Trials 1 and 2) 
Adverse Reactions 
BENRALIZUMAB (N= 822) % 
Placebo (N=847) % 
Headache 
8 
6 
Pyrexia 
3 
2 
Pharyngitis* 
5 
3 
Hypersensitivity reactions† 
3 
3 
 
Adverse reactions from Trial 3 with 28 weeks of treatment with benralizumab (n = 73) or 
placebo (n = 75) in which the incidence was more common in benralizumab than placebo 
include headache (8.2% compared to 5.3%, respectively) and pyrexia (2.7% compared to 
1.3%, respectively). The frequencies for the remaining adverse reactions with benralizumab 
were similar to placebo. 
 
In Trials 1 and 2, injection site reactions (e.g., pain, erythema, pruritus, papule) occurred at a 
rate of 2.2% in patients treated with benralizumab compared with 1.9% in patients treated 
with placebo. As with all therapeutic proteins, there is potential for immunogenicity. The 
detection of antibody formation is highly dependent on the sensitivity and specificity of the 
assay. Additionally, the observed incidence of antibody (including neutralizing antibody) 
positivity in an assay may be influenced by several factors including assay methodology, 
sample handling, timing of sample collection, concomitant medications, and underlying 
disease. For these reasons, comparison of the incidence of antibodies to benralizumab in the 
studies described below with the incidence of antibodies in other studies or to other products 
may be misleading. 
 
Overall, treatment-emergent anti-drug antibody response developed in 13% of patients 
treated with benralizumab at the recommended dosing regimen during the 48 to 56 week 
treatment period. A total of 12% of patients treated with benralizumab developed neutralizing 
antibodies. Anti-benralizumab antibodies were associated with increased clearance of 
benralizumab and increased blood eosinophil levels in patients with high anti-drug antibody 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
titers compared to antibody negative patients. No evidence of an association of anti-drug 
antibodies with efficacy or safety was observed. The data reflect the percentage of patients 
whose test results were positive for antibodies to benralizumab in specific assays. 
 
Long-term animal studies have not been performed to evaluate the carcinogenic potential of 
benralizumab. Published literature using animal models suggests that IL-5 and eosinophils 
are part of an early inflammatory reaction at the site of tumorigenesis and can promote tumor 
rejection. However, other reports indicate that eosinophil infiltration into tumors can promote 
tumor growth. Therefore, the malignancy risk in humans from an antibody that binds to IL- 
5Rα such as benralizumab is unknown. 
 
Animal Data 
In a prenatal and postnatal development study, pregnant cynomolgus monkeys received 
benralizumab from beginning on GD20 to GD22 (dependent on pregnancy determination), on 
GD35, once every 14 days thereafter throughout the gestation period and 1-month 
postpartum (maximum 14 doses) at doses that produced exposures up to approximately 310 
times that achieved with the MRHD (on an AUC basis with maternal IV doses up to 30 mg/kg 
once every 2 weeks). Benralizumab did not elicit adverse effects on fetal or neonatal growth 
(including immune function) up to 6.5 months after birth. There was no evidence of treatment- 
related external, visceral, or skeletal malformations. Benralizumab was not teratogenic in 
cynomolgus monkeys. Benralizumab crossed the placenta in cynomolgus monkeys. 
Benralizumab concentrations were approximately equal in mothers and infants on 
postpartum day 7, but were lower in infants at later time points. Eosinophil counts were 
suppressed in infant monkeys with gradual recovery by 6 months postpartum; however, 
recovery of eosinophil counts was not observed for one infant monkey during this period. 
 
Human Data 
Of the total number of patients in clinical trials of benralizumab, 13% (n = 320) were 65 and 
over, while 0.4% (n=9) were 75 and over. No overall differences in safety or effectiveness 
were observed between these patients and younger patients, and other reported clinical 
experience has not identified differences in responses between the elderly and younger 
patients, but greater sensitivity of some older individuals cannot be ruled out. 
 
CTCAE Version 5 will be utilized for toxicity evaluation. 
 
 
15.1 
Serious Adverse Event (SAE) Reporting 
An adverse event is considered serious if it results in ANY of the following outcomes: 
• 
Death 
• 
A life-threatening adverse event 
• 
An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
• 
Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or participant and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition 
 
Note: Hospital admission for a planned procedure/disease treatment is not considered an 
SAE. 
 
SAE reporting is required as soon as the participant starts investigational 
treatment/intervention. SAE reporting is required for 30-days after the participant’s last 
investigational treatment/intervention. Any event that occur after the 30-day period that is 
unexpected and at least possibly related to protocol treatment must be reported. 
 
Please note: Any SAE that occurs prior to the start of investigational treatment/intervention 
and is related to a screening test or procedure (i.e., a screening biopsy) must be reported. 
 
All SAEs must be submitted in PIMS. If an SAE requires submission to the HRPP office per 
IRB SOP RR-408 ‘Reporting of Serious Adverse Events’, the SAE report must be submitted 
within 5 calendar days of the event. All other SAEs must be submitted within 30 calendar 
days of the event. 
The report should contain the following information: 
• 
The date the adverse event occurred 
• 
The adverse event 
• 
The grade of the event 
• 
Relationship of the adverse event to the treatment(s) 
• 
If the AE was expected 
• 
Detailed text that includes the following 
o An explanation of how the AE was handled 
o A description of the participant’s condition 
o Indication if the participant remains on the study 
• 
If an amendment will need to be made to the protocol and/or consent form 
• 
If the SAE is an Unanticipated Problem 
 
 
15.2 
External AE Reporting 
Adverse Event Reporting Period 
All AEs/SAEs, irrespective of attribution of causality, must be reported. 
 
AE reporting, irrespective of seriousness, ends 30 days after the last dose of the study drug. 
 
SAEs considered related to study drug(s) or study procedures occurring after the end of the 
AE reporting period (as defined above) must be reported. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
 
If an SAE is present at the last study visit, the SAE should be followed to resolution or until 
the Investigator assesses the subject as stable, or the subject is lost to follow-up or 
withdraws consent. Resolution/stable means the subject has returned to baseline state of 
health or the Investigator does not expect any further improvement or worsening of the event. 
Assessment of Adverse Events 
 
Investigators will assess the occurrence of AEs and SAEs at all subject evaluation timepoints 
during the study. All AEs and SAEs whether volunteered by the subject, discovered by study 
personnel during questioning, or detected through physical examination, or other means, will 
be recorded in the subject’s medical record and on the AE CRF. 
Each recorded AE or SAE will be described using CTCAE v5.0 , including , duration (eg, start 
and end dates), severity, grade, suspected relationship to the study drug, and any actions 
taken. 
Adverse events related to disease under study (cancer in this case) including disease 
progression will not be reported as SAE for Benralizumab. Since Benralizumab can cause 
hypersensitivity reactions including anaphylaxis involving the skin, any worsening of 
cutaneous reactions should be reviewed by the investigator in the context of possible 
hypersensitivity reactions and assessed with other suspect concomitant medications before 
reporting. 
Pregnancy 
 
Subjects should be instructed to immediately notify the investigator of any pregnancies. Any 
female subjects receiving study drug who become pregnant must immediately discontinue 
study drug. The investigator should counsel the subject, discussing any risks of continuing 
the pregnancy and any possible effects on the fetus. 
Overdose 
 
Study drug overdose is the accidental or intentional use of the drug in an amount higher than 
the dose being studied. An overdose or incorrect administration of study drug is not an AE 
unless it results in untoward medical effects. 
 
If the associated AE fulfills serious criteria, Investigators should report the event to the 
Sponsor within 5 days using the MSK SAE form. 
 
In the event that the subject received more than the recommended benralizumab dosage, the 
subject should be treated with appropriate supportive management to mitigate adverse 
effects. 
Expedited Reporting Requirements for SAEs 
 
Investigators should report any SAEs to AstraZeneca within 5 calendar days using the MSK 
SAE form. The Sponsor will submit appropriate reports to applicable local regulatory 
agencies and to IRBs as required. MSK will notify AstraZeneca in parallel with submission to 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
the IRB and Regulatory Authorities for Suspected Unexpected Serious Adverse Reactions 
(SUSARs) and within fifteen (15) calendar days of awareness for other SAEs.. 
 
Follow-up information will be submitted to AstraZeneca within the same time frame as initial 
reports. 
 
Whenever possible, SAEs should be reported by diagnosis term not as a constellation of 
symptoms. 
 
If the primary cause of death is something other than disease progression, then the death 
should be reported as an SAE with the primary cause of death as the event AE term, as 
death is typically the outcome of the event, not the event itself. 
 
If study drug is discontinued because of an SAE, this information must be included in the 
SAE report. 
 
All SAEs are to be submitted to the AstraZeneca Product Safety mailbox: 
AEMailboxClinicalTrialTCS@astrazeneca.com 
 
Type and Duration of Follow-up of Subjects after Adverse Events 
All AEs and SAEs that are encountered during the protocol-specified AE reporting period 
should be followed to resolution, or until the investigator assesses the subject as stable, or 
the subject is lost to follow-up or withdraws consent. 
 
Reporting Requirements at the End of the Study 
MSK will Provide AstraZeneca, at latest within two weeks after Database Lock, a final 
unblinded line listing of all SAEs notified to regulatory authority and AstraZeneca 
during the study for safety event reconciliation. 
i. 
The email subject line MUST contain: ESR-19-14427 the study acronym (if 
possible) and the text “End of study reconciliation” 
ii. 
Studies with more than 50 SAEs should provide unblinding randomization data in 
xml-format 
 
The final end of study line listings should be sent using a secure email, to the AstraZeneca 
Data Entry Site (DES): 
AE-MailboxDCR-TCS@astrazeneca.com 
 
Final end of study line listings may also be faxed using the same subject line as above for 
sending emails to: 
o 
Preferred Fax Number: +1 302 886 4114 
o 
Backup fax number: +46 31 776 37 34 
 
16.0 PROTECTION OF HUMAN PARTICIPANTS 
16.1 
Privacy 
MSK’s Privacy Office may allow the use and disclosure of protected health information 
pursuant to a completed and signed Research Authorization form. The use and disclosure of 
protected health information will be limited to the individuals/entities described in the 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
Research Authorization form. A Research Authorization form must be approved by the IRB 
and Privacy Board (IRB/PB). 
The consent indicates that individualized de identified information collected for the purposes 
of this study may be shared with other qualified researchers. Only researchers who have 
received approval from MSK will be allowed to access this information which will not include 
protected health information, such as the participant’s name, except for dates. It is also 
stated in the Research Authorization that their research data may be shared with others at 
the time of study publication. 
 
16.2 
Data Management 
A Clinical Research Coordinator (CRC) will be assigned to the study. The responsibilities of 
the CRC include project compliance, data collection, abstraction and entry, data reporting, 
regulatory monitoring, problem resolution and prioritization, and coordinating the activities of 
the protocol study team. 
 
The data collected for this study will be entered into Medidata. Source documentation will be 
available to support the computerized patient record. Research blood collection for biomarker 
analysis and photographic data will be deidentified; will be labelled with patient study IDs to 
preserve links to clinical data. Canfield imaging systems Inc will be used to store 
photographic data. 
 
16.3 
Quality Assurance 
Weekly registration reports will be generated to monitor patient accruals and completeness of 
registration data. Routine data quality reports will be generated to assess missing data and 
inconsistencies. Accrual rates and extent and accuracy of evaluations and follow-up will be 
monitored periodically throughout the study period and potential problems will be brought to 
the attention of the study team for discussion and action. 
 
16.4 
Data and Safety Monitoring 
The Data and Safety Monitoring Plan utilized for this study must align with the MSK DSM 
Plan, where applicable. 
The Data and Safety Monitoring (DSM) Plans at Memorial Sloan Kettering were approved by 
the National Cancer Institute in August 2018. The plans address the new policies set forth by 
the NCI in the document entitled “Policy of the National Cancer Institute for Data and Safety 
Monitoring of Clinical Trials.” 
There are several different mechanisms by which clinical studies are monitored for data, 
safety and quality. At a departmental/PI level there exists procedures for quality control by 
the research team(s). Institutional processes in place for quality assurance include protocol 
monitoring, compliance and data verification audits, staff education on clinical research QA 
and two institutional committees that are responsible for monitoring the activities of our 
clinical trials programs. The committees: Data and Safety Monitoring Committee (DSMC) for 

Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
Phase I and II clinical trials, and the Data and Safety Monitoring Board (DSMB) for Phase III 
clinical trials, report to the Deputy Physician-in-Chief, Clinical Research. 
During the protocol development and review process, each protocol will be assessed for its 
level of risk and degree of monitoring required. 
The MSK DSMB monitors phase III trials and the DSMC monitors non-phase III trials. The 
DSMB/C have oversight over the following trials: 
• 
MSK Investigator Initiated Trials (IITs; MSK as sponsor) 
• 
External studies where MSK is the data coordinating center 
• 
Low risk studies identified as requiring DSMB/C review 
The DSMC will initiate review following the enrollment of the first participant/or by the end of 
the year one if no accruals and will continue for the study lifecycle until there are no 
participants under active therapy and the protocol has closed to accrual. The DSMB will 
initiate review once the protocol is open to accrual. 
17.0 
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Memorial Sloan Kettering Cancer Center 
IRB Number: 20-344 A(13) 
Approval date: 13-Aug-2024 
 
18.0 
APPENDICES 
Appendix A: Eosinophil-related Adverse Event Grading (CTCAE v5.0) 
Appendix B: Skindex-16 
Appendix C: ECOG Performance Status 
Appendix D: PRO-CTCAE for Skin Events 
Appendix E: RegiSCAR Scoring System for Diagnosing DRESS Syndrome