Biological Insights Fuel Novel Treatments for Rare Non-Melanoma Skin and Oral Cavity Cancers (Part 3)

Biological Insights Fuel Novel Treatments for Rare Non-Melanoma Skin and Oral Cavity Cancers

This article is Part 3 of our three-part series summarizing how MSK’s biological insights and expertise fuel innovative treatment approaches for patients with rare head and neck cancers. In Part 3 below, we  summarize MSK-led advances in non-melanoma skin of the head and neck and oral cavity cancers. Part 1 discusses rare salivary gland cancers and Part 2 covers rare thyroid cancers.

“While localized cutaneous squamous cell carcinomas and basal cell carcinomas are common, the presence of locally advanced disease with regional lymph node involvement or distant metastatic disease is rare,” said MSK head and neck oncologist Lara Dunn, MD.

Below are two examples of MSK-exclusive trials initiated and led by Dr. Dunn — a study of an innovative virotherapy for patients with advanced cutaneous squamous, basal cell, or Merkel cell carcinomas, and a study of a targeted immunotherapy approach for advanced squamous cell carcinoma with remarkable interim results showing improved responses and a significant reduction in treatment-related morbidities.

MSK Discovery Leads to Clincial Trial of Innovative Virotherapy

Dr. Dunn currently leads the MSK-exclusive trial of the oncolytic virus MQ710 for patients with advanced solid tumors, including cutaneous squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma. The trial (NCT05959074) began mid-2023 and aims to enroll 56 participants.

MSK dermatologist Liang Deng, MD, PhD, developed MQ710 in her lab and collaborated on its production with the biotech firm IMVAQ. The novel therapy is a multi-transgene expressing modified vaccinia virus Ankara-based virotherapy. For many years, members of Liang Deng Lab have focused on understanding how poxviruses like the vaccinia virus evade detection by the immune system and genetically engineering them to improve their ability to provoke immune responses. For example, in their recent paper in Nature Communications, Dr. Deng and colleagues discovered that deleting the protein E5 from vaccinia improved its immunogenicity. (1)

“This first-in-human trial of MQ710 is homegrown at MSK, from lab discovery to the clinic,” said Dr. Dunn. “Right now, we’re testing monotherapy dose escalation. Once we establish the maximum tolerable dose, we will expand the study to include patients with cancers for which anti-PD1 inhibitor therapy is not yet approved, followed later by MQ710 combined with pembrolizumab in approved indications.”

Remarkable Results for Neoadjuvant Therapy

At the 2023 Amercian Society of Clinical Oncology annual meeting, Dr. Dunn presented remarkable interim observations from an investigator-initiated trial of neoadjuvant therapy in patients with locoregionally advanced head and neck squamous carcinomas arising in the oral cavity, oropharynx, nasal cavity, paranasal sinuses, larynx or hypopharynx, for whom standard-of-care treatment would involve definitive surgery followed by adjuvant radiation plus concurrent chemotherapy.

The MSK-exclusive trial (NCT04722523) is ongoing, seeking to enroll 30 patients. Study participants receive a neoadjuvant regimen of four drugs — a platinium-based chemotherapy with cetuximab plus the PD-1 inhibitor cemiplumab over 10 weeks before surgery. The extensiveness of the surgical resection can be modified based on response. Further, post-operative radiation-based treatment can be omitted in patients with remarkable pathology responses or downstaging.

Interim results showed the neoadjuvant treatment regimen led to notable pathologic downstaging, a reduction in the extent of surgeries required, and many patients avoided adjuvant radiotherapy. (2)

Specifically, among 10 patients evaluated, eight had stages T3 or T4 disease, and five were staged as N2b/c. Pathologic downstaging was observed in 9 out of 10 patients (90%) after neoadjuvant therapy: 60% had a major pathologic response, and 40% had a complete pathologic response. Among five patients eligible for omitting adjuvant radiation therapy, four had adjuvant radiation omitted, and three received adjuvant cemiplimab. Further, 7 of 10 patients who typically would have required a free flap did not require the procedure. (2)

“So far, this neoadjuvant approach has allowed patients to have descalation of surgery, which often causes significant functional impairment and disfigurement, as well as avoid adjuvant radiation that carries significant toxicities,” said Dr. Dunn. “The median time from surgery has surpassed two years since the trial began in early 2021, and all patients remain disease-free to date.”

“This study was a full effort across the disease management team, all dedicated to the same goal of improving outcomes while limiting toxicities, whenever possible,” Dr. Dunn said. “We also hope that on-treatment tissues collected in this study will lead to new insights that drive further clinical research.”

Learn more about MSK clinical trials for head and neck cancers.

Access disclosures for Dr. Dunn

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  1. Yang N, Wang Y, Dai P, et al. Vaccinia E5 is a major inhibitor of the DNA sensor cGAS. Nat Commun. 2023;14(1):2898.
  2. Wong W, Cracciolo JR, Riaz N, et al. Neoadjuvant cemiplimab with platinum-doublet chemotherapy and cetuximab to de-escalate surgery and omit adjuvant radiation in locoregionally advanced head & neck squamous cell carcinoma (HNSCC).
  3. Poster presented at American Society of Clinical Oncology, June 2-6, 2023; Chicago, IL. Abstract 6019.