38th Annual Miami Breast Cancer Conference: Interim safety evaluation of same-day dosing of eflapegrastim in patients with early-stage breast cancer (ESBC) receiving docetaxel and cyclophosphamide (TC)

Interim safety evaluation of same-day dosing of eflapegrastim* in patients with early-stage breast cancer (ESBC) receiving docetaxel and cyclophosphamide (TC)

Lee S. Schwartzberg1, Lyndah K. Dreiling2, Jawad Francis3, Nishan Tchekmedyian4, Hlalah Osama5, Manuel Modiano6, Kyounghwa Bae2, Francois Lebel2, Shanta Chawla2

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

BACKGROUND

Eflapegrastim

• • Patients receiving chemotherapy are at risk of developing neutropenia (CIN) that can lead to FN and/or infection, necessitating dose delays and dose reductions, which can affect clinical outcomes.1,2

• • Clinical Practice Guidelines recommend the use of G-CSF as primary prophylaxis when the anticipated risk of FN is high.

• • G-CSF including long-acting agents, is administered 24 hours after chemotherapy, which requires patients to return to the clinic the next day.

• • Eflapegrastim (ROLONTIS®) is a novel long-acting G-CSF, produced by covalent conjugation of a human G-CSF analog and IgG4 Fc fragment, linked via a short polyethylene glycol linker.3,4

• • The increased FcRn-mediated transcytosis of eflapegrastim observed in preclinical studies may enhance its bioavailability post-chemotherapy allowing dosing on the same day as chemotherapy.5

Key Exclusion Criteria

• • Prior exposure or known sensitivity to G-CSF

• • History of bone marrow or hematopoietic stem cell transplant

• • Radiotherapy, surgery or treatment with investigational agent within 30 days prior to enrollment

Study Endpoints

• • Primary Endpoint:

  - Duration of Grade 4 neutropenia (ANC <0.5×109/L) in Cycle 1

• • Secondary Endpoints:

  - Incidence of Grade 3 febrile neutropenia (FN) in Cycle 1

  - Safety

INTERIM SAFETY EVALUATION

Per protocol

RESULTS

Table 2. Severe Neutropenia in Cycle 1

Table 3. Adverse Events Overview

* Grade 4

Note: All 9 patients received Cycle 2 chemotherapy

• • Arm 1: ANC recovery is more rapid as compared to Arms 2 and 3

  * Serious AEs:

  1 patient - cholecystitis acute, nephrolithiasis, Urinary tract infection bacterial; 1 patient - sepsis; and 1 patient - hypertensive crisis

  • • Arm 1

  METHODS

  Figure 1. Study Design

  Key Inclusion Criteria

  • • Patients with histologically confirmed stage I-IIIA early-stage breast cancer (ESBC)

    - ECOG Performance Score <=2

    - Candidates for neoadjuvant or adjuvant cyclophosphamide and docetaxel (TC)

  • • Age ≥ 18 years

  RD-ROL-0032

  Safety evaluation proceeded following completion of Cycle 1 for the first 3 patients in all treatment arms. Treatment arm(s) were to be stopped for further enrollment if one of the following criteria were met:

  • • 2 of 3 patients reported Grade 4 neutropenia and DSN > 1 day

  • • 2 of 3 patients reported febrile neutropenia in Cycle 1 and/or occurrence of any eflapegrastim-related Grade 4 AE

  Additional Safety Considerations

  • • Incidence of Grade 3/4 AEs in Cycle 1

    DEMOGRAPHICS

  • • Three patients each were randomized to Arm 1, Arm 2, or Arm 3.

  • • All patients were evaluable for safety

  Table 1. Demographics

  Characteristic	Arm 1 (0.5 hrs) (N=3)	Arm 2 (3 hrs) (N=3)	Arm 3 (5 hrs) (N=3)
  Age (years), Mean	48.7	63.7	59.3
  Weight (kg), Mean	73.5	115.5	70.5
  Gender (F/M), n/n	3/0	3/0	2/1
  ECOG Performance Status, n
  0	2	1	2
  1	1	2	1

• • Arms 2 and 3: ANC nadir is deeper and longer as compared to Arm 1

Figure 2. ANC Profiles in each Treatment Arm

*Eflapegrastim is an investigational drug not approved by the FDA

-

Positive early data showing ANC rapid recovery in Arm 1

- Met the prespecified interim safety evaluation criteria and therefore supports the expansion of this arm to 15 patients

-

The overall safety profile was similar to previously seen in large randomized studies when GCSF was given 24hrs after chemotherapy3,4

• • Arms 2 and 3

-

ANC nadir appears deeper and longer than in Arm 1

- Arm 2-3 did not meet the prespecified criteria, leading to stopping enrollment

Overall

- Early results are promising but a larger number of patients need to be studied before feasibility in humans is established

• 1. Dale DC, et al. A systematic literature review of the efficacy, effectiveness, and safety of filgrastim. Support Care Cancer 2018; 26: 7-20.

• 2. Denduluri N, et al. Dose Delays, Dose Reductions, and Relative Dose Intensity in Patients With Cancer Who Received Adjuvant or Neoadjuvant Chemotherapy in Community Oncology Practices. J Natl Compr Canc Netw 2015; 13: 1383-93.

• 3. Schwartzberg LS, et al. Eflapegrastim, a Long-Acting Granulocyte-Colony Stimulating Factor for the Management of Chemotherapy-Induced Neutropenia: Results of a Phase III Trial. The Oncologist. 2020;25:1-9.

• 4. Cobb PW, 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 Med 2020; 9: 6234-6243.

• 5. Barrett JA, et al. Eflapegrastim's enhancement of efficacy compared with pegfilgrastim in neutropenic rats supports potential for same-day dosing. Exp Hematol 2020; 92: 51-61.

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