Tislelizumab + Pamiparib + Chemoradiation for Head and Neck Cancer

Overseen By Cancer Trial Intake

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must not be taking: CYP3A inducers, St. John's Wort

Disqualifiers: Active tuberculosis, HIV, Hepatitis B, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 11

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest and most effective dose of a combination treatment for individuals with recurrent head and neck cancer, meaning the cancer has returned after previous treatment. The treatment combines two drugs, tislelizumab (an immunotherapy drug) and pamiparib (a PARP inhibitor), with standard chemotherapy and radiation. Participants will receive varying doses to identify which combination works best with the fewest side effects. Those whose head and neck cancer has returned and require additional local treatment may be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take certain medications like strong CYP3A inducers or herbal remedies like St. John's Wort. It's important to discuss your current medications with the study team to ensure there are no interactions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that over 3,900 patients have tested tislelizumab, either alone or with other treatments. These studies found that tislelizumab is generally well-tolerated, though some patients experienced side effects. Common side effects include fatigue, fever, and rash.

Research has also examined pamiparib's safety, finding it to have a manageable safety profile when combined with other medicines. While side effects can occur, they are usually not severe. Reported side effects include nausea, low blood cell counts, and fatigue.

As this study is in an early phase, it focuses on determining the right dose with the fewest side effects. Researchers continue to gather information on the safety of these treatments when used with chemoradiation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Tislelizumab, Pamiparib, and chemoradiation for head and neck cancer because this regimen has a unique approach. Unlike the standard treatments, which typically involve surgery, radiation, and chemotherapy alone, this combination includes Tislelizumab, an immune checkpoint inhibitor that helps the immune system target cancer cells more effectively. Additionally, Pamiparib is a PARP inhibitor, which can potentially enhance the effects of chemoradiation by making cancer cells more sensitive to treatment. This dual approach of boosting the immune response while also increasing the effectiveness of radiation and chemotherapy is what sets this treatment apart and fuels optimism among researchers.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that tislelizumab may help treat head and neck cancers. In earlier studies, patients with head and neck squamous cell carcinoma (HNSCC) lived longer and had better disease control when treated with tislelizumab. This treatment is known for its effectiveness and safety in these cancers.

Pamiparib, when combined with other treatments, has also shown promise in stopping tumor growth and even shrinking some tumors. The combination of pamiparib with other therapies has been linked to a significant survival rate in patients with high-risk cancer. In this trial, participants will receive different doses of pamiparib alongside tislelizumab and chemoradiation to determine the most effective and safe dose combination. These findings suggest that using tislelizumab and pamiparib together, along with chemoradiation, might effectively treat recurring head and neck cancer. ^{2 5 6 7 8}

Who Is on the Research Team?

Ari Rosenberg, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adults with recurrent head and neck cancer who've had prior treatments. They must be in good physical condition, not pregnant or breastfeeding, willing to use contraception if necessary, and have no active autoimmune diseases or infections like HIV/Hepatitis B/C. Patients with certain high-risk features after surgery may also join.

Inclusion Criteria

My throat cancer has been tested positive for HPV.

I agree to use birth control during and for 6 months after treatment if I'm sexually active with women who can become pregnant.

Women of childbearing potential must agree to follow instructions for highly effective method(s) of contraception for the duration of treatment and for 180 days after the last dose of study drug(s)

Exclusion Criteria

I do not have active lung problems like fibrosis or uncontrolled lung disease.

I have an active tuberculosis infection.

I have cancer that has spread to my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Dose

Participants receive one dose of tislelizumab (200 mg) 15 days before chemoradiotherapy

2 weeks

1 visit (in-person)

Chemoradiotherapy

Participants receive pamiparib in combination with 5-FU and hydroxyurea, plus radiation therapy over a period of 5 weeks

5 weeks

Daily visits for radiation

Rest Period

Participants rest for roughly 8 days without study drugs or radiation

1 week

Maintenance Treatment

Participants receive tislelizumab (200 mg) for 12 months by IV over 30 minutes every 6 weeks

12 months

Every 6 weeks (in-person)

Follow-up

Participants return to the clinic for follow-up every 4 months for 2 years, every 6 months for the next 2 years, and then once a year for the rest of their life

Long-term

Every 4 months for 2 years, every 6 months for the next 2 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Chemoradiation
• Pamiparib
• Tislelizumab

Trial Overview

The study tests the safety and best dose of tislelizumab (an immune therapy) combined with pamiparib (a targeted drug) plus standard chemoradiotherapy in patients whose head and neck cancer has returned. Participants will receive treatment for about 15 months followed by regular clinic visits for up to life-long monitoring.

How Is the Trial Designed?

Group I: Dose-Finding Group 3: Dose Level 3 (Part 1 of Study) Experimental Treatment 5 Interventions

The purpose of part 1 is to determine the best tolerated dose of study drugs with the least side effects. Dose escalation means that some participants will receive a different (higher) dose than other participants depending on when they join the study. This is to determine side effects at different doses and find a dose that will be safe to give to all participants. Participants in this group will receive: 1. One dose of tislelizumab (200 mg) 15 days before chemoradiotherapy (CRT) given intravenously (by IV), which means through a vein. 2. Chemoradiotherapy over a period of 5 weeks. During each cycle of CRT, participants will receive: * Pamiparib (40 mg twice daily on days 0-5 of each 14 -day cycle) along with 5FU and hydroxyurea for 5 days. * Radiation will also be given two times a day for 5 days 3. After CRT, participants will rest for roughly 8 days without study drugs or radiation then they will receive tislelizumab (200 mg) for 12 months by IV over 30 minutes every 6 weeks.

Group II: Dose-Finding Group 2: Dose Level 2 (Part 1 of Study) Experimental Treatment 5 Interventions

The purpose of part 1 is to determine the best tolerated dose of study drugs with the least side effects. Dose escalation means that some participants will receive a different (higher) dose than other participants depending on when they join the study. This is to determine side effects at different doses and find a dose that will be safe to give to all participants. Participants in this group will receive: 1. One dose of tislelizumab (200 mg) 15 days before chemoradiotherapy (CRT) given intravenously (by IV), which means through a vein. 2. Chemoradiotherapy over a period of 5 weeks. During each cycle of CRT, participants will receive: * Pamiparib (20 mg twice daily on days 0-5 of each 14 -day cycle) along with 5FU and hydroxyurea for 5 days. * Radiation will also be given two times a day for 5 days 3. After CRT, participants will rest for roughly 8 days without study drugs or radiation then they will receive tislelizumab (200 mg) for 12 months by IV over 30 minutes every 6 weeks.

Group III: Dose-Finding Group 1: Dose Level 1 (Part 1 of Study) Experimental Treatment 5 Interventions

The purpose of part 1 is to determine the best tolerated dose of study drugs with the least side effects. Dose escalation means that some participants will receive a different (higher) dose than other participants depending on when they join the study. This is to determine side effects at different doses and find a dose that will be safe to give to all participants. Participants in this group will receive: 1. One dose of tislelizumab (200 mg) 15 days before chemoradiotherapy (CRT) given intravenously (by IV), which means through a vein. 2. Chemoradiotherapy over a period of 5 weeks. During each cycle of CRT, participants will receive: * Pamiparib (20 mg daily on days 0-5 of each cycle) along with 5FU and hydroxyurea for 5 days. * Radiation will also be given two times a day for 5 days 3. After CRT, participants will rest for roughly 8 days without study drugs or radiation then they will receive tislelizumab (200 mg) for 12 months by IV over 30 minutes every 6 weeks.

Group IV: Dose Expansion Group ( Part II of Study) Experimental Treatment 5 Interventions

Part 2 (dose expansion phase): The purpose of this part is to continue to evaluate the dose of study drugs that is the best tolerated and has the least side effects. This part will start once the dose is selected from part 1. Enrollment in this part of the study is dependent on when participants join the study. Approximately 18 subjects will be enrolled in Part 2.

Chemoradiation is already approved in China for the following indications:

Approved in China as Baizean for:

• Classical Hodgkin’s lymphoma (cHL)
• Locally advanced or metastatic urothelial carcinoma (UC)
• Locally advanced or metastatic non-small cell lung cancer (NSCLC)
• Advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors
• Locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)
• Recurrent or metastatic nasopharyngeal cancer (NPC)

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

In a study of 16 patients with locally advanced head and neck cancer, the combination of the PARP inhibitor olaparib (at a recommended dose of 25 mg twice daily), cetuximab, and radiation therapy was well tolerated, showing promising response rates and reduced radiation dermatitis.

The two-year overall survival rate was 72%, indicating that this treatment regimen may be effective for high-risk patients, although continued smoking during therapy was linked to higher recurrence rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final Report of a Phase I Trial of Olaparib with Cetuximab and Radiation for Heavy Smoker Patients with Locally Advanced Head and Neck Cancer. Karam, SD., Reddy, K., Blatchford, PJ., et al.[2019]

In a study involving 180 patients with advanced solid tumors, the combination of pamiparib and tislelizumab demonstrated an overall objective response rate (ORR) of 20%, with the highest response (47.4%) observed in patients with triple-negative breast cancer (TNBC) who had BRCA1/2 mutations or homologous recombination deficiency.

While the treatment showed promising antitumor activity, it was associated with a significant incidence of treatment-emergent adverse events, with 61.7% of patients experiencing grade 3 or higher side effects, indicating that while the therapy is effective, careful monitoring for safety is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-expansion stage of a multicentre, open-label, phase I trial. Friedlander, M., Mileshkin, L., Lombard, J., et al.[2023]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a study of adult patients with metastatic head and neck squamous cell cancer, substituting 5-fluorouracil (5-FU) with a taxane in a pembrolizumab-based treatment regimen did not increase toxicity or worsen survival outcomes.

Patients receiving the taxane combination experienced significantly lower rates of mucositis and elevated creatinine levels compared to those on the 5-FU regimen, indicating a better safety profile for the taxane approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer. Lee, B., Chehab, SS., Fan, W., et al.[2023]

In a phase Ia clinical trial involving 32 patients with advanced head and neck cancer, atezolizumab demonstrated a tolerable safety profile, with 66% of patients experiencing treatment-related adverse events, but no grade 5 events reported.

The treatment showed promising efficacy, with 22% of patients achieving objective responses and a median overall survival of 6.0 months, indicating potential benefits regardless of HPV status or PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. Colevas, AD., Bahleda, R., Braiteh, F., et al.[2022]

The combination of pamiparib (a PARP inhibitor) and tislelizumab (an anti-PD-1 antibody) was generally well tolerated in a study of 49 patients with advanced solid tumors, with a recommended phase 2 dose established as tislelizumab 200 mg every 3 weeks plus pamiparib 40 mg twice daily.

Out of the participants, 20% achieved an objective response, including two complete responses, indicating that this combination therapy may provide clinical benefits and warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trial. Friedlander, M., Meniawy, T., Markman, B., et al.[2020]

Chemotherapy remains the primary treatment for recurrent and metastatic head and neck squamous cell carcinoma, with the current standard being a combination of cisplatin, 5-fluorouracil, and cetuximab for fit patients.

Immunotherapy options like nivolumab and pembrolizumab have become new standards in second-line treatment, showing improved overall survival, but further research is needed to identify predictive markers for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. Karabajakian, A., Toussaint, P., Neidhardt, EM., et al.[2019]

In a small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

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