Neoadjuvant Pembrolizumab in Cutaneous Squamous Cell Carcinoma

NCT05025813 | Recruiting Phase 2 DMC

• 1 other identifier: Ladwa59935
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

Cutaneous Squamous Cell Carcinoma (cSCC) is typically associated with a high tumour mutation burden, with the majority caused by Ultraviolet (UV) exposure (Pickering et al., 2014). The use of this trial using neoadjuvant Pembrolizumab in patients with cSCC who will otherwise undergo highly morbid radical surgical resection has multiple potential advantages, including:

1. 1.Reduction in surgical and radiotherapy morbidity by reducing tumour burden and allowing the appropriate selection of patients to undergo post-operative radiotherapy;
2. 2.Provision of immediate information about pathological response and
3. 3.Access to tissue to provide insight into resistance mechanisms and identification of biomarkers of response.

Conditions

Cutaneous Squamous Cell Carcinoma of the Head and Neck; Head and Neck Cancer

Keywords

Pembrolizumab; Immunotherapy; Radiation Therapy; Radiotherapy; Neoadjuvant; Radical Neck Dissection

Outcome Measures

Primary Outcomes (1)

• Assess the rate of pathological response to neo-adjuvant Pembrolizumab

  To assess the rate of pathological response of neo-adjuvant Pembrolizumab in patients with locally advanced, resectable cSCC. Response will be measured by reviewing tissue samples taken at either surgical resection or biopsy following 4 cycles of neo-adjuvant Pembrolizumab. A pathological complete response will show no viable tumour cells. Pathological response will be determined as: Major Pathological response (less than or equal to 10% viable tumour cells remaining following 4 cycles of Neo-adjuvant Pembrolizumab) Pathological Partial Response (11-50% of viable tumour cells remaining following 4 cycles of neo-Adjuvant Pembrolizumab) Pathological Stable and/or Progressive disease (greater than 50% viable tumour cells following 4 cycles of Neo-adjuvant Pembrolizumab)

  Will be assessed at the end of Cycle 4 (each cycle is 21 days) of Neo-adjuvant Pembrolizumab.

Secondary Outcomes (7)

• Objective response Rate

  Will be assessed at the end of Cycle 4 (each cycle is 21 days) of Neo-adjuvant Pembrolizumab

• Disease free survival

  From date of drug allocation until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 48 months

• Overall Survival

  From date of drug allocation until the date of death from any cause, whichever came first, assessed up to 48 months

• Locoregional Recurrence

  From date of drug allocation until the date of first documented locoregional recurrence or date of death from any cause, whichever came first, assessed up to 48 months

• Distant Recurrence

  From date of drug allocation until the date of first documented distant recurrence or date of death from any cause, whichever came first, assessed up to 48 months

Other Outcomes (4)

• Rate of De-escalation of surgery or post-operative radiotherapy following neo-adjuvant pembrolizumab

  At the end of 4 cycles of neo-adjuvant pembrolizumab. Each cycle is 21 days.

• Pattern of failure

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years following last administration of study drug (4 years total)

• Cumulative occurrence of Second Primary Tumours (SPT)

  From date of drug allocation until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 48 months

Study Arms (1)

Arm A

EXPERIMENTAL

Neoadjuvant Pembrolizumab 4 cycles, 200mg IV Q3W followed by interval restaging: If restaging imaging positive will have Radical Neck Resection followed by Pembrolizumab 17 cycles, 200mg IV Q3W +/- External Beam Radiotherapy (if \>10% viable tumour cells at resection) If restaging imaging negative will have Mapping biopsy. If biopsy positive will proceed to Radical Neck dissection followed by Pembrolizumab 17 cycles 200mg IV, Q3W If biopsy negative will proceed to Pembrolizumab 17 cycles 200mg IV, Q3W

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Delivery of neo-adjuvant Pembrolizumab

Also known as: External Beam Radiation Therapy, Radical Neck Dissection

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of invasive cSCC that is locally advanced (Stage II-IV on AJCC 8th edition) assessed preoperatively as sufficiently high risk that they will warrant post-operatively RT (as recommended by MDT) who is a candidate for a complete resection.
• Note: Participants with tumors arising on cutaneous non-glabrous (hair-bearing) lip with extension onto vermillion (dry red lip) may be eligible after communication and approval from the principal investigator. Participants for whom the primary site is the nose may be eligible after communication and approval from the MDT if the primary site is skin, not nasal mucosa with outward extension to skin. Participants who have squamous cell parotid metastases and have been treated previously for cSCC are permitted. cSCC that has recurred in the same location after 2 or more surgical procedures are not eligible.
• Participants must have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days prior to the start of treatment.
• Participants must have adequate organ function
• Participants must have a tissue sample adequate for translational research. This tissue sample may be obtained from either a newly obtained core or excisional biopsy.
• Participants must have a life expectancy of greater than 6 months.
• Be at least 18 years of age on the day of signing the informed consent. 8. Female participants: Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for the participant to start receiving study medication.
• \- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 1 OR A WOCBP who agrees to use an adequate method of contraception during the treatment period and for at least 120 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
• \- The participant (or legally acceptable representative if applicable) must be willing and able to provide written informed consent for the trial. The participant may also provide consent for Future Biomedical Research. However the participant may participate in the main trial without participating in Future Biomedical Research.

You may not qualify if:

• Participant has metastatic/unresectable cSCC that cannot be potentially cured with surgical resection, radiotherapy, or with a combination of surgery and radiotherapy.
• Participant has any other histologic type of skin cancer other than invasive squamous cell carcinoma as the primary disease under study, eg, basal cell carcinoma that has not been definitively treated with surgery or radiation, Bowen's disease, merkel cell carcinoma, melanoma.
• Participants with any prior allogeneic solid organ or hematopoietic stem cell transplantations are excluded.
• Participant has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
• Participant has received prior systemic anti-cancer therapy including investigational agents for cSCC.
• Participant has received prior radiotherapy to the target lesion.
• Participant has received a live vaccine within 30 days prior to the first dose of trial drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed-virus vaccines and are allowed; however, intranasal influenza vaccines(eg, FluMist®) are live- attenuated vaccines and are not allowed.
• Participant is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.
• Note: Participants who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs) or has a diagnosis of immunodeficiency disorders (such as HIV disease or organ transplantation or hematologic malignancies associated with immune suppression).
• Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of trial drug.
• Participant has a diagnosis and/or has been treated for additional malignancy within the past 3 years prior to allocation.
• Note: Participants with cSCC of the skin that have undergone potentially curative therapy are not excluded if not related to current diagnosis.
• Note: Participants with basal cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer or melanoma in situ) that have undergone potentially curative therapy are not excluded.
• Note: Participants with low-risk early-stage prostate cancer, defined as below are not excluded: Stage T1c or T2a with a Gleason score 6 and a prostate-specific antigen (PSA) (10 ng/ml) either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to trial allocation.

Sponsors & Collaborators

• Queensland Health: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

RECRUITING

Related Publications (1)

• Ladwa R, Lee JH, McGrath M, Cooper C, Liu H, Bowman J, Gupta R, Cuscaden C, Nottage M, Clark JR, Le D, Pauley M, Kulasinghe A, Gonzalez-Cruz J, Porceddu SV, Hughes BGM, Panizza B. Response-Adapted Surgical and Radiotherapy De-Escalation in Resectable Cutaneous Squamous Cell Cancer Using Pembrolizumab: The De-Squamate Study. J Clin Oncol. 2025 Sep 10;43(26):2888-2896. doi: 10.1200/JCO-25-00387. Epub 2025 Jul 21.

  PMID: 40690729 DERIVED

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

pembrolizumab; Neck Dissection

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Lymph Node Excision; Surgical Procedures, Operative; Otorhinolaryngologic Surgical Procedures

Study Officials

• Rahul Ladwa, MD

  Queensland Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rahul Ladwa, MD

CONTACT

+61731765479; rahul.ladwa@health.qld.gov.au

Kym Bessell

CONTACT

+61731763962; desquamate@health.qld.gov.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist, PAH

Model Details: Multi-centre, open-labelled, non-randomised, single-arm phase 2 study of Pembrolizumab in participants aged 18 years or older with locally advanced (LA) Stage II-IV resectable cSCC.

Study Record Dates

• First Submitted: June 14, 2021
• First Posted: August 27, 2021
• Study Start: June 28, 2022
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2027
• Last Updated: August 1, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: Immediately following publication with no end date
• Access Criteria: Available for sub-study, meta analysis

Locations

AU (3)