SABCS: Open-label, phase 1 study to evaluate duration of severe neutropenia after same-day dosing of eflapegrastim in patients with breast cancer receiving docetaxel and cyclophosphamide

San Antonio Breast Cancer Symposium® - December 8-12, 2020 • Abstract #322

*Eflapegrastim is an investigational drug not approved by the FDA

Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia After the Same-Day, Varying Dosing Time Schedules of Eflapegrastim* Administration in Patients with Breast-Cancer Receiving Docetaxel and Cyclophosphamide (NCT04187898)

Lee S. Schwartzberg1, Jawad Francis2, Hlalah Osama3, Manuel Modiano4, Jayaram Bharadwaj5, Shanta Chawla6, Gajanan Bhat6, Francois Lebel6 and Nishan Tchekmedyian7

1West Cancer Center, Germantown, TN; 2Mercy Health Youngstown, Youngstown, OH; 3Bond & Steele Clinic, P.A., Winter Haven, FL; 4ACRC/Arizona Clinical Research Center, Tucson, AZ; 5Pacific Cancer Medical Center, Inc., Anaheim, CA; 6Spectrum Pharmaceuticals, Inc, Irvine, CA; 7Pacific Shores Medical Group, Long Beach, CA

INTRODUCTION

• As a standard of practice, G-CSF products require administration

24 hours after chemotherapy

• Eflapegrastim (ROLONTIS®) is a long-actinggranulocyte-colony

stimulating factor (G-CSF), consisting of a recombinant human

G-CSF analog conjugated to a human IgG4 Fc fragment via a

short polyethylene glycol linker. Eflapegrastim is not a biosimilar

and represents the first long-acting myeloid growth factor that is

the subject of a pending innovator biologics license application in

more than 18 years

• In two Phase 3 studies that randomized a total of 643 patients

with early-stage breast cancer (ESBC) to either eflapegrastim (3.6

mg GCSF n=314) or pegfilgrastim (6 mg G-CSF n=329) given ~ 24

• Phase 1, open-label,multi-center trial

• Intravenous (IV) administration of TC on Day 1 of each cycle will be as

follows:

- Docetaxel 75 mg/m2 IV, infusion time per institution's SOC

- Cyclophosphamide 600 mg/m2 IV, infusion time per institution's SOC

- Patients may receive premedications for chemotherapy prophylaxis

according to institutional standard of care (SOC).

• 13.2 mg/0.6 mL (3.6 mg G-CSF) fixed dose eflapegrastim administered

subcutaneously (SC) at 0.5, 3 or 5 hours after TC

• Blood for CBC and PK analysis will be drawn before TC dose on Day 1 and

post eflapegrastim dose at 1, 3, 6, and 8 hours (±15 min), 24, 48, and 72

hours (±2 hours), 144 hours (Day 7 ±1 day) and 192 hours (Day 9 ±1 Day),

STUDY DESIGN

Figure 1. Study Schema

	Additional CBC Samples Drawn Daily			22, Day
			Cycle	Cycle	Cycle
		Cycle 1,
					2,	3,	4,
		Days
					1Day	1Day	1Day
-30				15	21
1 2 3 4 5 6 7 8 9 10
Day

Screening

End of Study Visit

35 (±5) Days

From the last dose of TC/Eapegrastim

STATISTICAL METHODS

• Target accrual: 45 patients randomized 1:1:1 to 30 min, 3 hr and 5 hr dosing
• A sample size of 15 patients per dosing schedule arm was determined to provide adequate precision for the 95% CI of the DSN and secondary endpoints, including PK parameters
• The sample size produces a 2-sided 95% CI with a distance from the mean DSN to the limits that is equal to 0.554 using t-distribution when the estimated standard deviation is 1.0 days
• A safety evaluation will be performed once the first three patients in each arm have completed Cycle 1

hours after docetaxel and cyclophosphamide (TC) administration,

the duration of severe neutropenia (DSN) was statistically

noninferior in patients treated with eflapegrastim compared to

pegfilgrastim, despite eflapegrastim being given at 60% of the

G-CSF dose of pegfilgrastim1,2

• In preclinical studies with chemotherapy-induced neutropenic

rats compared to pegfilgrastim (Neulasta®), eflapegrastim showed

approximately 3-fold higher exposure in serum, and higher

exposure in bone marrow, at similar doses3

- The duration of neutropenia (DN) with eflapegrastim was

shown to be significantly shorter than with pegfilgrastim

when administered on either the same day or 24 hours post-

chemotherapy

- Additionally, DN with eflapegrastim was similar regardless of

whether it was administered on the same day as chemotherapy

and on Cycle 2, Day 1 (Day 22) before TC dose.

• Peripheral blood CD34+ counts will be drawn daily from Day 2 to Day 10

Key Inclusion Criteria

• Histologically confirmed (operable stage I-IIIA) patients with ESBC
• Candidates for neoadjuvant or adjuvant TC chemotherapy
• ≥18 years of age
• ECOG ≤2
• Adequate hematological, renal, and hepatic function

Key Exclusion Criteria

Chemotherapy

Administration

+

Eapegrastim

Dosing Time Starts from the End of TC Dosing Time

13.2 mg/0.6 mL

(3.6 mg G-CSF) · 0.5 hours · 3 hours

· 5 hours

If on Day 10 the ANC is

≤1.0 x 109/mL, CBC will be drawn daily until the ANC is

≥1.5 x 109/mL

PK & CBC Sample Draw

• Predose (before TC)
• Postdose (after Eapegrastim)
• • C1 D1: 1, 3, 6, and 8 hours (± 15 minutes)
  • C1 D2: 24 hours (±2 hours)
  • C1 D3: 48 hours (±2 hours)
  • C1 D4: 72 hours (±2 hours)
  • C1 D7: 144 hours (±1 day)
  • C1 D9: 192 hours (±1 day)
  • C2 D1: Day 22 predose (before TC dosing)

Safety
Follow
for
Cycleup
-
1	Visit

Safety
Follow
for
Study
-
up
	Visit

CURRENT ENROLLMENT

• Enrollment began in April 2020
• 9 of 45 patients have been enrolled to date

REFERENCES

1. Schwartzberg LS, Bhat G, Peguero J, et al. Eflapegrastim, a Long-ActingGranulocyte-Colony Stimulating Factor for the Management of Chemotherapy-Induced Neutropenia: Results of a Phase III Trial. The Oncologist. 2020;25:1-9
2. Cobb PW, Moon YW, Mezei K, et al. A Comparison of Eflapegrastim to Pegfilgrastim in the Management of Chemotherapy-Induced Neutropenia in Patients with Early-Stage Breast Cancer Undergoing Cytotoxic Chemotherapy (RECOVER): A Phase 3 Study. Cancer Medicine. 2020;00:1-10. https://doi.org/10.1002/cam4.3227
3. Barrett JA, Choi J, Lakshmikanthan S, et al. Eflapegrastim Enhanced Efficacy Compared to Pegfilgrastim in Neutropenic Rats Supports Potential for Same-Day Dosing. Exp Hematol. 2020; https://doi.org/10.1016/j.exphem.2020.09.199

or 24 hours post-chemotherapy

• Preclinical and clinical results suggest that the increased activity

of eflapegrastim may provide effective prophylaxis against

chemotherapy-induced neutropenia when administered on the

same day as chemotherapy

OBJECTIVES

• To assess the feasibility of eflapegrastim dosing on the same-day as docetaxel cyclophosphamide (TC) in patients receiving TC for treatment of ESBC
• Dose schedule finding assessment of eflapegrastim administration at either 0.5 hours, 3 hours, or 5 hours from the end of TC administration

• Recurrent/metastatic breast cancer
• Active concurrent malignancy
• Known sensitivity or previous reaction to E. coli-derived products, or any products to be administered during study
• Concurrent non-trial-related adjuvant cancer chemotherapy
• Exposure to a G-CSF agent within previous 3 months
• History of bone marrow or hematopoietic stem cell transplant
• Radiotherapy or surgery or investigational agent within 30 days
• Pregnant/breast-feeding

Endpoints

• Primary:
• • Duration of Grade 4 neutropenia (ANC <0.5×109/L) in Cycle 1
• Secondary:
• • Incidence of Grade 4 neutropenia (ANC <0.5×109/L) in Cycle 1
  • Time to recovery to ANC ≥1.5×109/L in Cycle 1
  • Incidence of Grade 3 febrile neutropenia in Cycle 1 (ANC <1.0×109/L and either a single temperature of >38.3°C (101.0°F) or a sustained temperature of ≥38.0°C (100.4°F) for more than 1 hour
  • Pharmacokinetics (PK) of eflapegrastim in Cycle 1
  • Incidence of neutropenic complications during Cycle 1
  • Safety
• Exploratory:
• • Peripheral blood CD34+

ACKNOWLEDGEMENTS

• This trial is being sponsored by Spectrum Pharmaceuticals, Inc
• Medical writing assistance was provided by Spectrum Pharmaceuticals Medical Affairs

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*Eflapegrastim is an investigational drug not approved by the FDA

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RD-ROL-0027