Neoadjuvant PD-1 Inhibitor and EGFR Inhibitor in Locally Advanced Cutaneous Squamous Cell Carcinoma

ConditionLocally Advanced Cutaneous Squamous Cell Carcinoma

Trial statusNot yet recruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorMelanoma and Skin Cancer Trials Limited

About this trial

The NEOPECS trial is a phase II prospective, single-arm, non-randomised interventional trial for patients with borderline resectable locally advanced cutaneous squamous cell carcinoma with a 6-participant safety lead in to ensure safety of the combination in the neoadjuvant setting across 3 sites in Australia.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male or female > 18 years of age and able to comply with treatment, assessment and follow up

Documentation of a locally advanced cutaneous squamous cell carcinoma diagnosis as evidenced by histopathology with available archival tissue. Locally Advanced cutaneous Squamous Cell Carcinoma (LASCC) defined as borderline resectable for surgery due to multiple recurrences, prior radiotherapy, large extension, bone erosion and/or deep infiltration beyond the subcutaneous tissue into muscle/nerve or, where curative resection may lead to unacceptable complications, morbidity or deformity, and ineligible for curative radiotherapy

Measurable disease in accordance with iRECIST criteria OR clinically measurable disease >1cm by caliper measurement. Patients with synchronous primary cutaneous squamous cell carcinoma (cSCC) tumours will be eligible.

Adequate bone marrow function with haemoglobin >100g/L, absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L). Blood transfusion is allowable.

Disqualifiers

Distant metastatic disease (M1) including visceral or distant nodal metastases

Prior receipt of checkpoint inhibitor therapy or anti-EGFR therapy for LASCC or any other malignancy

Uncontrolled medical/psychiatric co-morbidity as per investigator that may jeopardize the ability of the patient to undergo trial procedures with reasonable safety

Uncontrolled autoimmune disease requiring active immune-suppression within 1 year of enrolment

Trial design

Design model

Single group

Treatments tested in this trial

Cetuximab
Drug
Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR). EGFR is over-expressed in many human cancers, including colorectal cancers.
Cemiplimab
Drug
Cemiplimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the programmed cell death-1 (PD-1) receptor and blocks its interaction with its ligands programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Engagement of PD-1 with its ligands PD-L1 and PD-L2, which are expressed by antigen presenting cells and may be expressed by tumour cells and/or other cells in the tumour microenvironment, results in inhibition of T cell function such as proliferation, cytokine secretion, and cytotoxic activity. Cemiplimab potentiates T cell responses, including antitumour responses, through blockade of PD-1 binding to PD-L1 and PD-L2 ligands.

Treatment groups

27 Participants

are divided into 1 treatment group

Group A: Cetuximab and CemiplimabExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Preliminary activity

The primary preliminary activity endpoint will be the achievement of clinical downstaging from borderline resectable status to either resectable status or surgery avoidance due to complete metabolic response with no residual pathological disease as deemed by Multi-Disciplinary Team (MDT) consensus evaluation following up to 4 cycles of neoadjuvant therapy.

Time frame

3 months

Secondary outcomes

Treatment safety and feasibility as assessed by NCI CTCAE v5

Safety and feasibility by assessment of Common Terminology Criteria for Adverse Events (CTCAE) V5.0 with the incidence of ≥ Grade 3 adverse events, \< Grade 3 adverse events and SAEs and AEs leading to study treatment discontinuation.

Time frame

12 months

Treatment safety and feasibility as assessed by rate of R0 resection

Safety and feasibility by assessment of change in rate of R0 resection. R0 resection is defined no residual tumour in surgically removed specimen of curative intent per local and central pathology review.

Time frame

12 months

Pathological response rate

Preliminary efficacy by assessment of pathological response rate, including complete (0% residual tumour cells) and major (0-10% residual tumour cells) pathological responses, by blinded central pathology review. Complete pathological response (pCR) defined as absence of viable tumor cells in surgical specimen. Major pathological response (MPR) defined as 0-10% viable tumor cells in surgical specimen.

Time frame

12 months

Overall response rate (ORR)

Preliminary efficacy by assessment of overall response rate (ORR) as per Modifed Response Evaluation Criteria in Solid Tumors for immune based therapeutics (iRECIST) criteria or investigator caliper assessment where disease is un-measurable by CT or MRI modalities

Time frame

12 months

Other outcomes

To explore the relationship between cancer-immune cell-stroma interactions using spatial transcriptomics and single cell RNA sequencing and outcome.

Time frame

3 months

Patient reported outcomes as assessed by EORTC QLQ-C30

The European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) will be utilized to assess the quality of life of cancer patients measured from 0-4 (Not at all - Very Much).

Time frame

36 months

Patient reported outcomes as assessed by FoP-Q-SF

The Fear-of-Progression Questionnaire - Short Form (FoP-Q-SF) will be utilized to assess fear of cancer progression measured from 1-5 (never - very often).

Time frame

36 months

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Melanoma and Skin Cancer Trials Limited

Lead sponsor

Source ClinicalTrials.gov

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