Sequential Toripalimab and Paclitaxel in Patients With Head and Neck Squamous Cell Cancer (HNSCC) and Poor Performance Status

A Phase 2 Pilot Study of the Role of Sequential Immune Checkpoint Inhibitor Toripalimab and Chemotherapy Paclitaxel in Patients With HNSCC and ECOG Performance Score of 2

The goal of this clinical trial is to learn if the drug Toripalimab can prime the tumor to optimize response to Paclitaxel in HNSCC patients with a decrease performance status in a way that make both drugs well tolerated and improve partial or complete response rate over each treatment. The main questions it aims to answer are:

• What is the response rate of the cancer to paclitaxel after priming with toripalimab
• What is the time to progression if we continue to cycle between toripalimab and paclitaxel
• What is the impact on the patient's quality of life and overall survival

Toripalimab treatment will be administered on an outpatient basis. Toripalimab will be given in the clinic on Day 1. Intravenous (IV) infusions will be given every three weeks thereafter for the first seven weeks of the study. Administration follows standard of care.

Paclitaxel treatment will be administered on an outpatient basis as per standard of care once weekly for a total of eight weeks during Weeks 8-15 of each cycle. Premedication and administration follow standard of care. After eight weeks of chemotherapy, the participant finishes the cycle with two weeks of rest (no treatment).

This will be repeated for a total of 51 weeks total of 3 cycles (each cycle is 17 weeks) We will study sequential ICI and CT on HNSCC, and the impact on quality of life in addition to studying the tumor microenvironment. Participants undergo an optional biopsy before and after eight weeks of weekly paclitaxel. To explore the cytotoxic signature, we will calculate the enrichment scores for canonical cytotoxic markers (GZMA, GZMB, GZMK, GNLY, IFNG, PRF1 and NKG7). To estimate the signature of collagen formation, we will calculate enrichment scores using the gene lists from the REACTOME_COLLAGEN_FORMATION pathway (msigdb.v7.5.1.symbols.gmt; https://www.gsea-msigdb.org/gsea/index.jsp). To explore the cell type contexts, we will perform principal component analysis (PCA) and then uniform manifold approximation and projection (UMAP) using the RunPCA and RunUMAP functions based on the cell type proportion inferred by spatial transcriptomics deconvolution (STRIDE). Results will be summarized using descriptive statistics, including mean, median, standard deviation, range, count, and percentage, as appropriate.

Inclusion Criteria:

• Participants must have histologically confirmed HNSCC deemed to be metastatic or incurable by the treating physician. Participants can have incurable disease at presentation or have been treated with definitive curable surgical resection, chemoradiotherapy (CRT), or both, then relapsed with non-curable disease. Participants diagnosed with HNSCC stage IV-C or metastatic/non-resectable, relapsed disease are eligible for this study

• Participant must have measurable disease, defined by RECIST v1.1.

• Participant must be able to understand a written informed consent document and be willing to sign it.

• Participants must be 18 years of age or older.

• Participant must have a life expectancy of at least six months.

• Participant must have an ECOG performance score of 2.

• Participant must have:

  1. Total bilirubin ≤ 3 times upper limit of normal (ULN)
  2. Hemoglobin > 8 g/dL. Transfusion is permitted
  3. Absolute neutrophil count (ANC) > 1.0 K/mm3. Granulocyte colony-stimulating factor (G-CSF) is NOT permitted

• Paclitaxel has known embryo- and fetotoxic effects. Therefore, women of childbearing potential must agree to avoid becoming pregnant and male participants should avoid impregnating a female partner and donating sperm starting at initiation of treatment up until at least 30 days after last dose of toripalimab or paclitaxel.

Exclusion Criteria:

• Participants with known untreated brain metastases will be excluded from this clinical trial. Stable brain metastases will be allowed, and it will be confirmed by stable brain MRI with and without contrast within 8 weeks of signing consent.

• Participants with uncontrolled chronic obstructive pulmonary disease (COPD), heart disease, or autoimmune disease, in the opinion of the treating physician.

• Participants who are taking any other investigational drugs.

• Participants who are taking prednisone or equivalent steroid >10 mg per day prior to the start of treatment.

  • The washout period is at the treating physician's discretion.
  • Once participants are on study, they may be treated with steroids and other immunosuppressants per standard of care.

• Participants with a history of allergic reactions attributed to toripalimab, paclitaxel, or medicines containing Kolliphor ELP (Polyoxyl 35 Castor Oil, NF).

• Participants who are pregnant or breastfeeding. If a breastfeeding participant would like to be part of this study, breastfeeding must be discontinued.

• Participants who have end-stage renal failure are eligible for this study unless they have had a kidney transplant.

• Participants that do not agree to be followed according to the study protocol or have cognitive or physical inability to follow the treatment plan.