Tislelizumab + Pamiparib + Chemoradiation for Head and Neck Cancer

Overseen By Cancer Trial Intake

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Chicago

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

Disqualifiers: Active tuberculosis, HIV, Hepatitis B, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability and maximum tolerated dose of tislelizumab in combination with pamiparib plus chemoradiotherapy (chemotherapy and radiation) in individuals with recurrent head and neck cancer, which means that the person's cancer has come back after treatment. Participation in the study should last for about 15 months while participants receive tislelizumab and chemoradiotherapy with pamiparib. Afterwards, they will return to the clinic for follow up every 4 months for 2 years, every 6 month for the next 2 years, and then once a year for the rest of their life.

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.

What data supports the effectiveness of the drug combination Tislelizumab, Pamiparib, and Chemoradiation for head and neck cancer?

Research shows that combining drugs like pamiparib and tislelizumab can be effective in treating advanced solid tumors, and similar drugs like pembrolizumab have shown promise in treating head and neck cancer by improving survival rates. This suggests that the combination of these drugs with chemoradiation might also be effective for head and neck cancer. ^{1 2 3 4 5}

Is the combination of Tislelizumab and Pamiparib safe for use in humans?

The combination of Tislelizumab and Pamiparib has been studied for safety in patients with advanced solid tumors. The research indicates that this combination is generally safe and tolerable in humans, although specific side effects and their severity can vary. ^{1 2 6 7 8}

What makes the Tislelizumab + Pamiparib + Chemoradiation treatment unique for head and neck cancer?

This treatment is unique because it combines Tislelizumab, an immunotherapy drug that helps the immune system attack cancer cells, with Pamiparib, a PARP inhibitor that prevents cancer cells from repairing themselves, alongside traditional chemoradiation. This combination aims to enhance the effectiveness of treatment by targeting cancer cells in multiple ways. ^{1 2 4 7 8}

Research Team

Ari Rosenberg, MD

Principal Investigator

University of Chicago

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Chemoradiation (Radiation)
• Pamiparib (PARP Inhibitor)
• Tislelizumab (PD-1 Inhibitor)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

References

1. England 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of atezolizumab in head and neck cancer: results from a phase I trial. [2022]

3. England 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Chemotherapy for recurrent/metastatic head and neck cancers. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

6. England 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. [2020]

7. United States 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. [2019]

8. Greece 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. [2023]