Combination Therapy for Head and Neck Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
Must not be taking: Investigational agents, Immunosuppressants
Disqualifiers: Additional malignancy, Cell therapy, Organ transplant, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
Phase 1b open-label study to evaluate the safety of selected TIL (TBio-4101) delivered after lymphodepleting chemotherapy and followed by intravenous (IV) bolus aldesleukin (IL-2) and pembrolizumab for patients with advanced HNSCC who have initially progressed on pembrolizumab or pembrolizumab/platinum chemotherapy.
Do I need to stop my current medications to join the trial?
Yes, you need to stop any systemic therapy, including anti-cancer monoclonal antibodies, at least 3 weeks before the TIL harvest or apheresis. Also, you cannot be on chronic anti-coagulant therapy that can't be changed to one with a short half-life.
What data supports the effectiveness of the drug pembrolizumab in treating head and neck cancer?
Is the combination therapy for head and neck cancer safe for humans?
Pembrolizumab, a part of the combination therapy, has been evaluated for safety in patients with head and neck cancer. Common serious side effects include pneumonia, breathing difficulties, confusion, vomiting, and immune-related issues like lung inflammation, liver inflammation, and thyroid problems. The overall safety profile was considered acceptable for patients with this type of cancer.13567
What makes the combination therapy for head and neck cancer unique?
This treatment combines pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with TBio-4101, a therapy involving tumor-infiltrating lymphocytes (TILs) that are designed to target and destroy cancer cells. This combination aims to enhance the body's immune response against head and neck cancer, offering a novel approach compared to traditional chemotherapy and EGFR inhibitors.12589
Eligibility Criteria
This trial is for adults with advanced head and neck squamous cell carcinoma (HNSCC) who have seen their cancer progress despite treatment with pembrolizumab or a combination of pembrolizumab and platinum-based chemotherapy.Inclusion Criteria
I am willing and able to undergo a procedure to collect my blood cells.
The effects of TBio-4101 on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of study drug administration.
I have a score of 1 or more for pembrolizumab treatment eligibility.
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Exclusion Criteria
Participants who are receiving any other investigational agents.
Participants with a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
I have not taken drugs like nivolumab or pembrolizumab before.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
TIL Harvest/Standard of care Treatment
Participants undergo tumor harvest for TIL and receive 2 to 3 cycles of pembrolizumab or pembrolizumab/platinum chemotherapy
6-9 weeks
TBio-4101 Treatment
Participants receive TBio-4101 infusion, followed by IL-2 administration and pembrolizumab on specified days
Up to 2 years
Multiple visits for IL-2 and pembrolizumab administration
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 5 years
Treatment Details
Interventions
- Aldesleukin (Cytokine)
- Cyclophosphamide (Chemotherapy)
- Fludarabine (Chemotherapy)
- Pembrolizumab (Checkpoint Inhibitor)
- Platinum based chemotherapy (Chemotherapy)
- TBio-4101 (CAR T-cell Therapy)
Trial OverviewThe study tests TBio-4101, a type of tumor-infiltrating lymphocyte therapy, after chemo that reduces immune cells. It's followed by aldesleukin to boost the immune system and more pembrolizumab to help fight the cancer.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: TIL Harvest/Standard of care Treatment PhaseExperimental Treatment2 Interventions
Participants will undergo tumor harvest for TIL and then receive 2 to 3 cycles of pembrolizumab or pembrolizumab/platinum chemotherapy (cisplatin or carboplatin / 5-FU) as per standard of care.
Group II: TBio-4101 TreatmentExperimental Treatment6 Interventions
Participants without radiographic response (progressive disease) after pembrolizumab or pembrolizumab/platinum chemotherapy, and who meet eligibility requirements, will transition to receive TBio-4101. Participants will receive TBio-4101 infusion and after completion of TBio-4101 infusion, IL-2 will be administered every 8 hours, for up to 6 doses. Finally, pembrolizumab will be administered on Day 14, Day 35, and Day 56 and Q6W (beginning Week 12) thereafter for up to 2 years until discontinuation.
Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:
🇺🇸 Approved in United States as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇪🇺 Approved in European Union as KEYTRUDA for:
- Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
- Melanoma
- Non-small cell lung cancer (NSCLC)
- Urothelial carcinoma
- Colorectal cancer
- Gastric cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
🇬🇧 Approved in United Kingdom as KEYTRUDA for:
- Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
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Who Is Running the Clinical Trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
Turnstone Biologics, Corp.Industry Sponsor
References
Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. [2021]Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response.
Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. [2022]Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1 that have recently been approved in pretreated recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK).
Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. [2023]To evaluate potential synergistic effect of pembrolizumab with radiotherapy (RT) compared with a standard-of-care (SOC) cetuximab-RT in patients with locally advanced-squamous cell carcinoma of head and neck (LA-SCCHN).
Pembro Ups Survival in PD-L1-positive HNSCC. [2019]In a phase III trial, first-line treatment with single-agent pembrolizumab led to deep and durable responses among patients with head and neck tumors that expressed high levels of PD-L1.
Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]Until recently, palliative options for the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited efficacy with substantial toxicity. The development of novel immune checkpoint inhibitors has challenged the standard treatment. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the interaction between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2. In August 2016, the US FDA approved the use of pembrolizumab in R/M HNSCC following disease progression on or after platinum-containing chemotherapy. This review highlights the pharmacology, therapeutic efficacy and tolerability data relevant to the use of pembrolizumab for the treatment of R/M HNSCC. Readers will gain greater insight into the HNSCC tumor microenvironment, available biomarkers, and learn about important clinical considerations associated with the use of pembrolizumab and similar immune checkpoint inhibitors.
FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. [2019]On August 5, 2016, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp., Kenilworth, NJ) for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. Approval was based on the objective response rate (ORR) and duration of response (DoR) in a cohort of patients in a nonrandomized multi-cohort trial (KEYNOTE-012) that included 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. Patients received either intravenous pembrolizumab 10 mg/kg every 2 weeks or 200 mg every 3 weeks. ORR was determined by independent review according to Response Evaluation Criteria in Solid Tumors 1.1. ORR was 16% (95% confidence interval 11, 22) with a complete response rate of 5%. DoR ranged from 2.4+ months to 27.7+ months. Twenty-three of 28 responding patients (82%) had response durations of ≥6 months. Safety was evaluated in 192 patients with HNSCC receiving at least one dose of pembrolizumab. Frequent (≥2%) serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders. The benefit-risk profile of pembrolizumab was considered acceptable in this patient population. As a condition of accelerated approval, Merck is required to conduct a confirmatory trial; this trial, KEYNOTE-040, is ongoing.
Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. [2019]There are few effective treatment options for patients with recurrent or metastatic head-and-neck squamous cell carcinoma. Pembrolizumab showed antitumour activity and manageable toxicity in early-phase trials. We aimed to compare the efficacy and safety of pembrolizumab versus standard-of-care therapy for the treatment of head-and-neck squamous cell carcinoma.
Pembrolizumab Monotherapy Versus Pembrolizumab Plus Chemotherapy in Patients With Head and Neck Squamous Cell Carcinoma. [2023]Pembrolizumab monotherapy and pembrolizumab with chemotherapy (combination therapy) are standard treatments for recurrent and metastatic head and neck squamous cell carcinoma (R/M-HNSCC). This study aimed to explore which of the two, pembrolizumab monotherapy or combination therapy is superior for long-term use.
Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. [2023]Pembrolizumab is used in patients with metastatic head and neck squamous cell carcinoma contingent upon the programmed death ligand-1 (PD-L1) combined positive score (CPS).