Immunoradiotherapy for Oropharyngeal Cancer

Recruiting at 2 trial locations

Overseen By Joseph A Califano, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Diego

Disqualifiers: Solitary lymph nodes < 3 cm

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

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

Compensation: Varies

Number of Visits: 11

Duration: 6 weeks

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating HPV-related throat cancer. It combines precise radiation therapy (stereotactic radiation) with immunotherapy to determine if this combination improves cancer response before surgery. The treatment may suit individuals with surgically removable HPV-related throat cancer who can undergo the specific therapies involved. By focusing on this group, researchers aim to enhance the effectiveness of standard treatments. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

A previous study found that stereotactic radiation was well-tolerated, with only about 6.6% of patients experiencing serious side effects, such as needing a feeding tube or developing a lung infection from inhaling food or liquid. Another study on pembrolizumab found it generally safe when used before surgery, with no new safety concerns. Ongoing research is examining the safety of evorpacept, which is designed to help the immune system fight cancer cells. Since this trial is in phase 2, earlier studies have shown some safety for the treatment. Overall, the treatments in this trial have been mostly well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for oropharyngeal cancer because it combines stereotactic body radiation therapy (SBRT) with the immunotherapy drugs Pembrolizumab and Evorpacept. Unlike traditional treatments that often rely heavily on surgery and chemotherapy, this approach aims to enhance the body's immune response to target and destroy cancer cells more effectively. SBRT delivers high doses of radiation precisely to the tumor, reducing damage to surrounding healthy tissue. Pembrolizumab, an immune checkpoint inhibitor, works by freeing up the immune system to attack cancer, while Evorpacept enhances this effect by preventing the tumor from evading immune detection. This combination not only targets the cancer more directly but also aims to improve patient outcomes with potentially fewer side effects.

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

This trial will evaluate the combination of stereotactic radiation therapy, Pembrolizumab, and Evorpacept for HPV-related throat cancer. Research has shown that combining precise radiation treatment with immunotherapy can improve outcomes for this condition. This radiation treatment offers a promising 5-year survival rate of 85% for patients. Pembrolizumab, a type of immunotherapy, has effectively treated head and neck cancers and improves survival when combined with standard treatments. Evorpacept enhances the immune system by helping immune cells locate and attack cancer cells more easily. Together, these treatments aim to strengthen the immune system's ability to fight cancer, potentially leading to better patient outcomes. ^{1 4 6 7 8}

Who Is on the Research Team?

Jospeh A Califano, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for individuals with early-stage HPV-related throat cancer (Stage I T1-2N1M0) that can be surgically removed. Participants must be able to safely undergo pre-surgery radiation and treatment with Evorpacept/Pembrolizumab.

Inclusion Criteria

My condition can be treated with surgery.

My cancer is early-stage HPV-related throat cancer.

I can safely undergo radiation and take Evorpacept/Pembrolizumab.

Exclusion Criteria

I have a single lymph node smaller than 3 cm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Stereotactic radiation therapy (SBRT) delivered to gross tumor volume

1 week

1 visit (in-person)

Treatment

Pembrolizumab and Evorpacept administered every three weeks for 2 cycles

6 weeks

2 visits (in-person)

Surgery

Surgical resection of primary tumor and neck dissection

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and quality of life post-treatment

3 years

Multiple visits (in-person and virtual) at 7, 11 weeks, and 3, 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Evorpacept
• Pembrolizumab
• Stereotactic Radiation

Trial Overview The study tests if targeting throat tumors with precise radiation alongside immunotherapy drugs, Evorpacept and Pembrolizumab, before surgery can improve the body's response to the cancer in those affected by HPV.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Stereotactic radiation therapy (SBRT (8GyX3)) will be delivered to gross tumor volume (GTV) +3mm, followed by Pembrolizumab 200 mg IV and Evorpacept 45 mg/kg IV every three weeks x 2 cycles followed by surgical resection of primary tumor and neck dissection.

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Published Research Related to This Trial

The two-step intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer resulted in favorable 5-year overall survival rates of 80% for stage I and 64% for stage IVA-B, indicating effective treatment across various stages of the disease.

Patients with HPV/p16-positive oropharyngeal cancer had significantly better overall survival compared to those who were HPV/p16-negative, highlighting the importance of HPV status in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-step Intensity-modulated Radiation Therapy for Oropharyngeal Cancer: Initial Clinical Experience and Validation of Clinical Staging. Tatebe, H., Doi, H., Ishikawa, K., et al.[2019]

A multi-institutional study involving 69 patients with early oropharyngeal cancer showed that intensity-modulated radiation therapy (IMRT) achieved a low 2-year local-regional failure rate of 9%, indicating high tumor control rates without the use of chemotherapy.

While the treatment resulted in significant late toxicities, particularly xerostomia (dry mouth), the severity of these side effects decreased over time, with 55% of patients experiencing Grade 2 or higher xerostomia at 6 months, dropping to 16% by 24 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22). Eisbruch, A., Harris, J., Garden, AS., et al.[2022]

Frameless stereotactic body radiotherapy (SBRT) was found to be a safe and effective treatment option for boosting primary oropharyngeal cancers in 51 patients who were not suitable for standard brachytherapy, achieving 2-year local control, disease-free survival, and overall survival rates of 86%, 80%, and 82%, respectively.

The treatment was well tolerated with no severe (Grade 4 or 5) toxicities reported, and only 28% of patients experienced Grade 2 or higher late toxicity, indicating that SBRT can be a viable alternative with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy: a promising treatment option for the boost of oropharyngeal cancers not suitable for brachytherapy: a single-institutional experience. Al-Mamgani, A., Tans, L., Teguh, DN., et al.[2012]

Intensity-modulated radiotherapy (IMRT) for oropharyngeal squamous cell carcinoma showed promising 5-year local control rates, with 87% overall and varying by cancer stage, indicating its efficacy in managing advanced disease.

The treatment resulted in a 5-year cause-specific survival rate of 85% and an overall survival rate of 76%, with a relatively low incidence of severe late complications (8%), suggesting that IMRT is a safe and effective option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy for oropharyngeal squamous cell carcinoma. Mendenhall, WM., Amdur, RJ., Morris, CG., et al.[2022]

Intensity modulated radiation treatment (IMRT) for oropharyngeal squamous cell carcinoma showed excellent locoregional control, with a 3-year locoregional progression-free survival rate of 98.8% among 66 patients treated between 2000 and 2004.

Despite the high locoregional control, there was a concerning rate of distant metastasis, with a 3-year distant metastasis-free survival rate of only 80.4%, indicating a need for further research into systemic treatments for patients at risk of distant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing failure patterns in oropharyngeal squamous cell carcinoma treated with intensity modulated radiotherapy and implications for future research. Yao, M., Nguyen, T., Buatti, JM., et al.[2006]

Intensity-modulated radiotherapy (IMRT) using helical tomotherapy for oropharyngeal carcinoma showed promising clinical outcomes, with a 3-year overall survival rate of 80% and a progression-free survival rate of 68% among 93 patients followed for a median of 40 months.

The treatment effectively preserved parotid gland function, with only 23% of patients experiencing Grade 2 xerostomia (dry mouth) after 2 years, indicating a favorable safety profile alongside its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical results of definitive intensity-modulated radiation therapy for oropharyngeal cancer: retrospective analysis of treatment efficacy and safety. Kimura, K., Kodaira, T., Tomita, N., et al.[2018]

In a study comparing 26 patients receiving radiotherapy with cetuximab (cet-RT) to 27 patients receiving chemotherapy (chemo-RT) for HPV+ oropharyngeal cancer, both groups showed similar functional outcomes and quality of life over time, despite some initial worsening in swallowing and quality of life scores.

The results suggest that using cetuximab instead of chemotherapy for treatment de-intensification in HPV+ oropharyngeal cancer may not provide significant advantages, as both treatment approaches yielded excellent clinical outcomes without notable differences in patient functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparisons of dysphagia and quality of life (QOL) in comparable patients with HPV-positive oropharyngeal cancer receiving chemo-irradiation or cetuximab-irradiation. Samuels, SE., Tao, Y., Lyden, T., et al.[2018]

Citations

1. ir.alxoncology.com ir.alxoncology.com/news-releases/news-release-details/alx-oncology-reports-encouraging-clinical-data-evorpacept

Release Details The Phase 1/2 IST is an ongoing, open-label, single arm clinical trial designed to evaluate the safety, tolerability, and efficacy of evorpacept.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30133535/

ALX148 blocks CD47 and enhances innate and adaptive ... ALX148 binds CD47 from multiple species with high affinity, inhibits wild type SIRPα binding, and enhances phagocytosis of tumor cells by macrophages.

3. alxoncology.com alxoncology.com/wp-content/uploads/2020/06/ASH-Presentation-2017.pdf

ALX148 is a High Affinity SIRPα Fusion • ALX148 enhances the efficacy of antitumor and checkpoint inhibitor antibodies. After Chen and Mellman, 2013. ALX148 Inhibits the CD47-SIRPα Checkpoint.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03013218

A Study of Evorpacept (ALX148) in Patients With Advanced ... Study Overview. Brief Summary. A phase 1, dose escalation study of evorpacept (ALX148) in patients with advanced solid tumors and lymphoma.

5. globenewswire.com globenewswire.com/news-release/2024/04/09/2860415/0/en/ALX-Oncology-Reports-Encouraging-Clinical-Data-of-Evorpacept-in-Combination-with-Standard-of-Care-in-an-Ongoing-Phase-1-2-Clinical-Trial-in-Patients-with-Relapsed-or-Refractory-B-c.html

ALX Oncology Reports Encouraging Clinical Data of The Phase 1/2 IST is an ongoing, open-label, single arm clinical trial designed to evaluate the safety, tolerability, and efficacy of evorpacept ...

6. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/evorpacept

Definition of Evorpacept - NCI Drug Dictionary Upon administration, evorpacept binds to CD47 expressed on tumor cells and prevents the interaction of CD47 with its ligand SIRPa, a protein expressed on ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12370181/

A Phase I Trial of Evorpacept, Lenalidomide and Rituximab ... Evorpacept (ALX148) is a novel CD47 blocker that abrogates interactions between lymphoma cells and SIRPα+ macrophages. Methods. Adult patients ...

8. go.drugbank.com go.drugbank.com/drugs/DB17573

Evorpacept: Uses, Interactions, Mechanism of Action Evorpacept is under investigation in clinical trial NCT04755244 (A Study of Evorpacept (ALX148) With Venetoclax and Azacitidine for Acute ...