Cemiplimab + ISA101b for HPV-Related Throat Cancer

Not currently recruiting at 71 trial locations

Overseen By Sonja Visscher

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ISA Pharmaceuticals

Must not be taking: Immunosuppressants, Anti-PD-1 antibodies

Disqualifiers: Brain metastases, Autoimmune disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments to determine their effectiveness for HPV-related throat cancer. Participants will receive either cemiplimab (an immunotherapy drug) with a new treatment called ISA101b or cemiplimab with a placebo to compare their effects. The goal is to assess how well these treatments work together against cancer that has returned or spread. The trial seeks individuals diagnosed with HPV16-positive throat cancer that has recurred or metastasized, who have already undergone certain therapies. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medications like steroids, you may need to stop them 14 days before starting the study drug.

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

Research shows that the combination of ISA101b and cemiplimab is generally well-tolerated. Studies found no severe side effects directly linked to this treatment. Using ISA101b with cemiplimab does not increase serious side effects compared to standard treatments like chemotherapy, suggesting it is generally safe for participants. Additionally, ISA101b has received fast-track designation from the FDA, indicating promise in early studies. Overall, the evidence suggests a positive safety profile for this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about cemiplimab combined with ISA101b for HPV-related throat cancer because it targets the immune system in a novel way. Unlike traditional treatments like surgery or radiation, cemiplimab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. When paired with ISA101b, a vaccine designed to enhance the immune response against HPV, it offers a two-pronged attack. This combination has the potential to be more effective and less invasive than the current standard of care, providing new hope for patients with this type of cancer.

What evidence suggests that this trial's treatments could be effective for HPV-related throat cancer?

In this trial, participants will receive either the combination of ISA101b and cemiplimab or a placebo with cemiplimab. Research has shown that using ISA101b with cemiplimab yields promising results for treating throat cancer caused by HPV. Specifically, earlier studies demonstrated that this combination helped 15.4% of patients whose cancer had worsened after other treatments. ISA101b is a cancer vaccine that enhances the immune system's ability to recognize and fight cancer cells. When combined with cemiplimab, a drug that boosts the immune system, it may help the body target and destroy cancer cells in HPV-related throat cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Bonnie Glisson, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults diagnosed with HPV16 positive recurrent or metastatic OPC (a type of throat cancer), whose tumors express a protein called PD-L1 and are suitable for first-line therapy with PD-1 blocking antibodies, or have progressed after chemotherapy. Participants must be in good physical condition (ECOG 0-1) and not have used certain immunosuppressive drugs recently. Women must test negative for pregnancy.

Inclusion Criteria

I have signed the consent form approved by the ethics committee.

My cancer is HPV16 positive, expresses PD-L1, and has either not been treated or progressed after chemotherapy.

Be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study

Exclusion Criteria

You have had an allergic reaction to cemiplimab or any of its ingredients.

I haven't taken high doses of steroids or other immune-weakening medicines in the last 14 days.

I haven't had cancer, except for certain skin, cervix, prostate, breast, or bladder cancers in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab plus placebo or cemiplimab plus ISA101b every 3 weeks for up to 24 months

24 months

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

What Are the Treatments Tested in This Trial?

Interventions

• Cemiplimab
• ISA101b
• Placebo

Trial Overview This phase 2 trial is testing the effectiveness of Cemiplimab combined with ISA101b versus Cemiplimab with a placebo in treating HPV16-positive OPC. Patients will be randomly assigned to one of these two groups without knowing which treatment they receive.

How Is the Trial Designed?

Group I: Active ISA101b and cemiplimab. Experimental Treatment 2 Interventions

ISA101b 3 times plus cemiplimab every 3 weeks for up to 24 months

Group II: Placebo and cemiplimab Placebo Group 2 Interventions

Placebo 3 times plus cemiplimab every 3 weeks for up to 24 months

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

ISA Pharmaceuticals

Lead Sponsor

Trials

5

Recruited

400+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

Cemiplimab-rwlc (Libtayo) is an FDA-approved immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC) that works by blocking the PD-1 receptor, enhancing the immune system's ability to fight tumors.

Clinical trials have shown that cemiplimab is effective in treating CSCC, although common side effects and safety issues were noted, highlighting the need for ongoing research to improve treatment outcomes and reduce toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab-rwlc as first and only treatment for advanced cutaneous squamous cell carcinoma. Ahmed, SR., Petersen, E., Patel, R., et al.[2019]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

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]

Cemiplimab (Libtayo®) is the first approved immunotherapy for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC) who cannot undergo surgery or radiotherapy, showing a clinically significant objective response rate in the phase II EMPOWER-CSCC 1 trial.

The treatment has a durable effect, with the median duration of response and overall survival not yet reached, and it has an acceptable safety profile, with manageable immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cemiplimab: A Review in Advanced Cutaneous Squamous Cell Carcinoma. Lee, A., Duggan, S., Deeks, ED.[2020]

Cemiplimab combined with radiation therapy, cyclophosphamide, and GM-CSF did not show improved efficacy compared to standard PD-1 inhibitor monotherapy in treating refractory and metastatic head and neck squamous cell carcinoma, based on a study of 15 patients.

The safety profile of the combination therapy was consistent with previous findings for cemiplimab alone, with no new safety concerns identified, although common side effects included fatigue and pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and Granulocyte Macrophage Colony-Stimulating Factor in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Babiker, H., Brana, I., Mahadevan, D., et al.[2021]

Pembrolizumab, an immune checkpoint inhibitor, has shown significantly improved overall survival in patients with relapsed and/or metastatic head and neck squamous cell carcinoma compared to the standard EXTREME regimen, indicating a promising shift in treatment options.

This review highlights the importance of understanding the mechanisms of immune checkpoint inhibitors, including their interaction with the immune system and the challenges posed by tumor heterogeneity and PD-L1 expression, which are crucial for optimizing patient selection for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential of Pembrolizumab in Metastatic or Recurrent Head and Neck Cancer: Evidence to Date. McCusker, MG., Orkoulas-Razis, D., Mehra, R.[2020]

In a study of 36 patients with resectable HPV-unrelated head and neck squamous-cell carcinoma, neoadjuvant pembrolizumab was found to be safe, with no serious adverse events reported during treatment.

The treatment resulted in a pathologic tumor response in 44% of patients, and the one-year relapse rate for those with high-risk pathology was significantly lower at 16.7%, compared to the historical rate of 35%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Uppaluri, R., Campbell, KM., Egloff, AM., et al.[2021]

Cemiplimab, administered as monotherapy or in combination with hypofractionated radiation therapy, showed a 10% objective response rate in patients with recurrent or metastatic cervical cancer, particularly in those with squamous histology, indicating its potential efficacy in this subgroup.

The most common side effects were diarrhea, fatigue, and hypokalemia, affecting 35%, 25%, and 25% of patients respectively, suggesting that while cemiplimab has anti-tumor activity, it also has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Rischin, D., Gil-Martin, M., González-Martin, A., et al.[2021]

In a study of 63 patients with recurrent/metastatic squamous cell carcinoma of the head and neck, the combination of carboplatin and pemetrexed demonstrated a median progression-free survival (PFS) of 5.1 months and a median overall survival (OS) of 9.4 months, indicating its efficacy as a treatment option.

Among patients with oropharyngeal cancer, particularly those with HPV-positive disease, the treatment showed even better outcomes, with a median PFS of 7.0 months and median OS of 17.1 months, highlighting the potential for improved survival in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin-pemetrexed in treatment of patients with recurrent/metastatic cancers of the head and neck; superior outcomes in oropharyngeal primaries. Malhotra, B., Bellile, EL., Nguyen, NP., et al.[2020]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03669718

Study Details | NCT03669718 | A Randomized Phase 2 ... This study will assess the ability of ISA101b to improve Overall Response Rate in subjects with HPV16 positive OPC, when combined with cemiplimab, ...

2. delta.larvol.com delta.larvol.com/Products/?ProductId=ed472f6a-e8f9-4d9f-a5d2-3d2a3bb4c291

ISA101b / ISA Pharma P2 data • Head and Neck Cancer • Oropharyngeal Cancer. Print; Email; More ... (cemiplimab) Combination in Head and Neck Cancer at the ASCO Annual Meeting 2023 ...

3. isa-pharma.com isa-pharma.com/promising-results-of-isa101b-and-libtayo-in-patients-whose-head-and-neck-cancer-progressed-on-anti-pd1-therapy/

The combination of ISA101b and Libtayo® shows ... The combination of ISA101b and cemiplimab in these patients resulted in an overall response rate (ORR) of 15.4%, as per investigator assessment.

4. withpower.com withpower.com/trial/phase-3-carcinoma-squamous-cell-10-2018-fc234

Cemiplimab + ISA101b for HPV-Related Throat Cancer This trial is testing a combination of a cancer vaccine and a drug to help the immune system fight HPV16 positive oropharyngeal cancer.

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04398524

Cemiplimab and ISA101b in Patients With Recurrent ... This study will assess the ability of ISA101b plus cemiplimab to improve Overall Response Rate in subjects who have progressed on prior anti-PD-1 therapy.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.6028

Phase 2 study of ISA101b (peltopepimut-S) and ... Grade 4-5 AEs related to study treatment did not occur. Median overall survival was 8.1 months (range 0.3-17.5). Conclusions: This treatment ...

7. cancernetwork.com cancernetwork.com/view/fda-gives-isa101b-fast-track-designation-for-hpv-16-oropharyngeal-cancer

FDA Gives ISA101b Fast Track Designation for HPV 16 ... ISA101b has received a fast track designation from the FDA for the treatment of patients with recurrent and metastatic human papillomavirus ...

8. isa-pharma.com isa-pharma.com/clinical-studies/

clinical studies To date, combinations with ISA101b were well-tolerated and safe, without increase in serious adverse events compared to chemotherapy or anti-PD-1 alone.

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02458-X/fulltext

878P Final results of a phase II study of peltopepimut-S ... The combination of peltopepimut-S and cemiplimab was well tolerated, and resulted a CBR of 56.3% and mOS of 11.3 months in patients with relapsed/metastatic ...