Replimune CERPASS Poster Presentation at SITC 2021

CERPASS: A randomized, controlled, open-label, phase 2 study of cemiplimab ± RP1 in patients with advanced cutaneous squamous cell carcinoma

Andrew Haydon1, Muhammad Alamgeer2, Daniel Brungs3, Frances Collichio4, Nikhil I. Khushalani5, Dimitrios Colevas6, Danny Rischin7, Ragini Kudchadkar8, Wanxing Chai-Ho9, Gregory Daniels10, Jose Lutzky11, Jenny Lee12, Samantha Bowyer13, Michael Migden14, Ann W. Silk15, Céleste Lebbé16, Jean-Jacques Grob17, Ignacio Melero18, Piyush Sheladia19, Praveen K. Bommareddy19, Shui He19, Claudia Andreu-Vieyra19, Matthew G. Fury20, Andrew Hill21

1The Alfred Hospital, Melbourne, Australia; 2Monash Medical Centre, Clayton, Australia; 3Southern Medical Day Care Centre, Wollongong, Australia; 4Lineberger Comprehensive Cancer Center, University Of North Carolina, Chapel Hill, NC, USA; 5Moffitt Cancer Center, Tampa, FL, USA;

6Stanford University School of Medicine, Stanford, CA, USA; 7Peter MacCallum Cancer Center and University of Melbourne, Melbourne, Australia; 8Winship Cancer Institute of Emory University, Atlanta, GA, USA; 9UCLA David Geffen School of Medicine, Los Angeles, CA, USA; 10UC San Diego Moores Cancer Center, La Jolla, CA, USA; 11University of Miami Sylvester Comprehensive Center, Miami, FL, USA; 12Chris O'Brien Lifehouse, Camperdown, Australia; 13Sir Charles Gairdner Hospital, Nedlands, Australia; 14MD Anderson Cancer Center, Houston, TX, USA; 15Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; 16Université de Paris, Department of Dermatology, CIC AP-HP Hôpital Saint Louis, Paris, France; 17Hôpital de la Timone Service de Dermatologie et Cancérologie Cutanée, Marseille, France; 18Departamento de Inmunologia and Inmunoterapia, Centro de Investigación Medica Aplicada, Universidad de Navarra, Pamplona, Spain, 19Replimune Inc, Woburn, MA, USA; 20Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 21Tasman Oncology Research, Southport, Australia.

Background

Trial Design

• Cutaneous squamous cell carcinoma (CSCC) is the

second most common type of skin cancer with an

approximate worldwide incidence of ~1.7M cases per

year; including 0.18M - 0.42M cases per year in the United

States [1,2].

• Although most CSCC patients have a favorable prognosis,

the disease has a greater propensity for aggressive

recurrences and the prognosis of locally advanced and/or

nodal and distant metastatic disease remains poor [3].

• Cemiplimab-rwlc is a the programmed death receptor-1

(PD-1) blocking antibody approved in USA and EU for the

treatment of patients with metastatic or locally advanced

• Target enrollment = 180
• 2:1 randomization favoring combination arm

Screening Randomization

	Cycle 1†	Cycle 2	Cycle 3	Cycle 3	Cycle 4 - 12
	D22, D43	D1, D22, D43
Day -21	D1, D22, D43	D1, D22, D43	D1	RP1 re-
						initiation‡

	RP1**	RP1**	RP1**	Cemiplimab	Cemiplimab
RP1*	+	+	+
	Cemiplimab	Cemiplimab	Cemiplimab

EOT, safety

and OS

follow-up

Cemiplimab

Cemiplimab

Cemiplimab

Cemiplimab

Cemiplimab

CSCC who are not candidates for curative surgery or

radiation therapy [4, 5].

• RP1 is an enhanced potency oncolytic HSV-1 which

expresses a fusogenic glycoprotein (GALV-GPR-) and

granulocyte macrophage colony stimulating factor (GM-

CSF) [6].

• In pre-clinical studies, RP1 monotherapy induces tumor

regression in both injected and distant/un-injected tumors

which is further enhanced by combining with anti-PD-1

antibody; thus the combination of RP1 and cemiplimab is

*First dose = 1 x 106 PFU/ml **Subsequent doses = 1 x 107 PFU/ml

† 1 Cycle = 63 days

‡RP1 re-initiation (up to 8 additional doses of RP1) can occur at any time during the 108 week treatment period after a 12-week RP1 dosing holiday, during which patients will receive cemiplimab alone. If no reinitiation occurs, patients may receive cemiplimab only from Cycle 3 D22 up to Cycle 12 D43.

Treatment period = 108 weeks

RP1 will be administered via direct intratumoral injection into superficial or subcutaneous lesions or into deep/visceral lesions using image guidance (e.g., ultrasound or CT imaging).

Cemiplimab 350 mg intravenous over 30 minutes every 21 days for up to 108 weeks.

expected to provide a synergistic effect.

• RP1 + nivolumab (a PD-1 inhibitor) has shown compelling

response rates and a good safety profile in patients with

melanoma and other non-melanoma skin cancers (NMSC)

including anti-PD-1 failed disease [7].

Objective

The primary objective of this study is to assess the safety and efficacy of cemiplimab monotherapy vs. RP1 + cemiplimab combination in patients with locally advanced or nodal or distant metastatic cutaneous squamous cell carcinoma (CSCC).

Methods

Phase 2 Open-label Randomized Global

Key Eligibility Criteria

Inclusion

• Histologically confirmed diagnosis of locally advanced or metastatic CSCC that was previously treated, not suitable candidates for radiotherapy, chemotherapy or surgery or have refused those treatments.
• At least 1 measurable lesion by study criteria and lesion(s) that are injectable, which individually or in aggregate are
  ≥ 1 cm longest in diameter.
• ECOG ≤1; ECOG 2 allowed if due to CSCC.
• Anticipated life expectancy > 12 weeks.
• Provide archival (within 6-12 months of screening date) or new biopsy (FFPE block or unstained slides) for central pathology review and biomarkers.

Exclusion

• Prior treatment with oncolytic therapy or PD-1/PD-L1 inhibitors or with other immune modulating agents.
• Active significant herpetic infections or prior complications of HSV-1.
• Untreated brain metastasis(es).
• SCC of the dry red lip (vermillion) or anogenital area and mixed histology is excluded unless predominantly CSCC.
• Ongoing or recent auto-immune disease requiring systemic immunosuppressive treatments, a diagnosis of immunodeficiency disorders, organ transplantation or hematologic malignancies linked with immune suppression.

Key Endpoints

• Primary

Objective response rate and complete response rate by independent review per RECIST v1.1 and clinical and composite response criteria.

• Secondary

Safety by CTCAE V5.0, PFS and OS.

• Exploratory

Comprehensive biomarker analysis using tumor biopsies and peripheral blood, including the assessment of RP1 biodistribution and shedding.

CERPASS is now recruiting patients. To learn more about enrolling your patient contact: [e-mail] or [phone].

Additional information could be obtained by visiting ClinicalTrials.Gov (NCT04050436).

References:

1.Urban K, et al. JAAD International.2021;2: 98-108. 2.Rogers HW, et al. Arch Dermatol.2010;146(3):283-7. 3.Rees JR, et al. Int J Cancer. 2015;137(4):878-884. 4.Migden MR, et al. Lancet Oncol. 2020;21(2):294-305. 5.Migden MR, et al. N Engl J Med. 2018;379(4):341-351. 6.Thomas S, et al. J Immunother Cancer. 2019;7(1):214. 7.Middleton M, et al. J Immunother Cancer.2020;8.

Acknowledgement:

Authors would like to thank patients for their participation in the trial. Authors would also like to acknowledge the contribution of April Dovholuk, Maggie Ascolillo, Alexandra Budden, Sejal Sachapara, Susan Boyer of Replimune for their contribution to the study.

Study Sponsor:

The study is sponsored by Replimune Group Inc, Woburn MA, USA.

Presented at the Society for Immunotherapy of Cancer's (SITC) 36th Annual Meeting, 10-14 November, 2021