IBRX-042 for HPV-Related Cancer

Recruiting at 2 trial locations

Overseen By Jayson Garmizo

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ImmunityBio, Inc.

Must not be taking: Systemic corticosteroids

Disqualifiers: Serious pulmonary disease, active hepatitis, others

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

Compensation: Varies

Number of Visits: 5

Duration: 9 weeks

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic daily treatment with systemic corticosteroids or medications that have adverse reactions with the study drug, you may need to stop those.

What data supports the effectiveness of the treatment IBRX-042 for HPV-related cancer?

Research shows that HPV-positive cancers, like those in the head and neck, often respond better to treatments like radiotherapy compared to HPV-negative cancers. This suggests that treatments targeting HPV-related pathways, like IBRX-042, could potentially be effective for HPV-related cancers. ^{1 2 3 4 5}

What is the safety profile of IBRX-042 (ibrutinib) in humans?

Ibrutinib, also known as IBRX-042, is generally well-tolerated but can cause side effects like atrial fibrillation (irregular heartbeat), diarrhea, fatigue, and nausea. Most side effects are mild, but some can be severe, especially when interacting with other drugs like verapamil. ^{6 7 8 9 10}

What is the purpose of this trial?

The goal of this clinical trial is to determine the maximum tolerated dose and to find out the side effects of a drug called IBRX-042 at different dose levels in patients with recurrent or progressive Human Papillomavirus (HPV) associated tumors. The main questions it aims to answer are: * What is the maximum tolerated dose of IBRX-042? * How well does the study drug treat cancer? * What effects the study drug may have on the human body and cancer? Participants will receive IBRX-042 at one of three dose levels every 3 weeks for a total of 3 injections. Participants will undergo tests, exams, and procedures that are part of standard of care and for study purposes. IBRX-042 will be administered by injection every 3 weeks for a total of 3 injections.

Research Team

Bobby Reddy, MD

Principal Investigator

ImmunityBio, Inc.

Eligibility Criteria

This trial is for adults aged 18-75 with HPV-associated cancers who've had at least one standard treatment. They must have a certain level of white blood cells, be able to consent, and provide a tumor sample. Good health status (ECOG 0 or 1) and managed side effects from previous treatments are required. Participants must agree to use effective contraception.

Inclusion Criteria

I can understand and sign the consent form as per the ethics committee's guidelines.

Agreement to practice effective contraception for female subjects of child-bearing potential and nonsterile males

My cancer is HPV-positive or shows p16 positivity.

Exclusion Criteria

History of autoimmune disease as determined by the Investigator

Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus, and/or hepatitis C virus

Known hypersensitivity to any component of the study medication(s)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IBRX-042 by injection every 3 weeks for a total of 3 injections

9 weeks

3 visits (in-person)

End-of-Treatment

Participants attend an end-of-treatment visit 30 (± 5) days after the last administration of study treatment

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a follow-up visit 6 months after the last dose and periodic contact for at least 1 year

6 months

1 visit (in-person), periodic contact every 3 months

Treatment Details

Interventions

• IBRX-042

Trial Overview The study tests the drug IBRX-042's highest dose that patients can tolerate without severe side effects in treating HPV-related tumors. It involves three injections every three weeks, along with regular tests and exams to monitor the drug's effect on cancer and the body.

Participant Groups

Group I: Second Dose Level Experimental Treatment 1 Intervention

Dose Cohort 2: IBRX-042 5e11 virus particles per dose

Group II: First Dose Level Experimental Treatment 1 Intervention

Dose Cohort 1: IBRX -042 1e11 virus particles per dose

Group III: De-escalation Dose Level Experimental Treatment 1 Intervention

Dose Cohort -1: IBRX-042 5e10 virus particles per dose

Who Is Running the Clinical Trial?

ImmunityBio, Inc.

Lead Sponsor

Trials

75

Recruited

5,000+

Richard Adcock

ImmunityBio, Inc.

Chief Executive Officer since 2024

Information not available

Dr. Patrick Soon-Shiong

ImmunityBio, Inc.

Chief Medical Officer since 2021

MD

Findings from Research

HPV-positive oropharyngeal cancer cells are more sensitive to proton therapy compared to HPV-negative cells, showing a higher number of unrepaired DNA double-strand breaks, which may enhance treatment effectiveness.

Proton therapy demonstrated greater cell-killing ability than X-ray therapy across all tested fraction sizes, with the relative biological effectiveness (RBE) influenced more by cell type and radiation fraction size than by HPV status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus status and the relative biological effectiveness of proton radiotherapy in head and neck cancer cells. Wang, L., Wang, X., Li, Y., et al.[2022]

In patients with stage III to IVb HPV-positive oropharyngeal cancer, active smokers had a significantly higher rate of distant metastases (22%) compared to never or former smokers (5%), indicating smoking status is a critical predictor of cancer progression.

Patients with T4 tumors also showed increased rates of distant metastases (15%) compared to those with T1 to T3 tumors (6%), and those treated with cetuximab-based bioradiotherapy had a higher rate of metastases (23%) compared to those receiving cisplatin-based chemoradiotherapy (5%), suggesting the need for intensified treatment strategies for these high-risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of distant metastasis in human papillomavirus-associated oropharyngeal cancer. Weller, MA., Ward, MC., Berriochoa, C., et al.[2018]

HPV-associated cancers have distinct molecular pathways that lead to cell immortalization, making them suitable targets for screening strategies aimed at reducing cancer burden.

Patients with HPV-positive cancers generally have a better prognosis compared to those with non-HPV positive cancers, highlighting the importance of timely HPV status diagnosis for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of HPV on the Pathobiology of Cancers. Kumar, R., Tanwar, P., Singh, AR., et al.[2019]

HPV-positive head and neck squamous cell carcinomas (HNSCC) show a significant decrease in cell proliferation and hypoxia levels after radiation treatment, indicating they are more radiosensitive compared to HPV-negative tumors.

The study suggests that the reduced hypoxic fraction in HPV-positive tumors post-irradiation may explain why hypoxic modifiers do not provide additional benefits in patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of radiation on cell proliferation and tumor hypoxia in HPV-positive head and neck cancer in vivo models. Sørensen, BS., Busk, M., Horsman, MR., et al.[2014]

A study identified distinct molecular profiles in a subset of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) tumors that correlate with poor treatment response, suggesting these tumors behave more like HPV- tumors.

The researchers developed a prognostic biomarker signature to help identify high-risk HPV+ OPSCC patients, which could lead to better treatment strategies and reduce unnecessary radiotherapy-related morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variations in HPV function are associated with survival in squamous cell carcinoma. Gleber-Netto, FO., Rao, X., Guo, T., et al.[2022]

A large-scale analysis of 16,196 serious adverse drug reaction reports identified 36 potential safety signals associated with ibrutinib, including ischemic heart diseases and fractures, highlighting the need for careful patient monitoring.

The study found that over half of the reports resulted in hospitalization, indicating that while ibrutinib is a standard treatment for B-cell malignancies, its safety profile requires further investigation to confirm these findings in broader populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database. Allouchery, M., Tomowiak, C., Lombard, T., et al.[2021]

In a study of 133 children and adolescents who received radiotherapy to the salivary glands, it was found that both acute and late side effects were significantly influenced by the maximum radiation dose, with higher doses leading to increased toxicity.

For every 1 Gray increase in radiation dose to the submandibular glands, there was a 4% increase in the odds of acute toxicities, highlighting the importance of dose management in minimizing side effects in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and late side effects to salivary glands and oral mucosa after head and neck radiotherapy in children and adolescents. Results of the "Registry for the evaluation of side effects after radiotherapy in childhood and adolescence". Bölling, T., Weege, J., Eich, HT., et al.[2015]

Ibrutinib, an oral anticancer medication, can cause severe side effects, such as diarrhea, when taken with the moderate CYP3A4 inhibitor verapamil, highlighting the importance of monitoring drug interactions.

This case emphasizes the need for careful prescription reviews for patients on ibrutinib to prevent adverse effects from potential interactions with CYP3A4 inhibitors, ensuring safer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse event potentially due to an interaction between ibrutinib and verapamil: a case report. Lambert Kuhn, E., Levêque, D., Lioure, B., et al.[2021]

Ibrutinib, an oral treatment for chronic lymphocytic leukemia, is generally well-tolerated but can cause side effects, including a rare case of grade 3 sensorineural polyneuropathy, as seen in a 63-year-old patient after 10 months of therapy.

After discontinuing ibrutinib due to neuropathy, the patient's symptoms improved, and he was able to resume treatment at a lower dose without severe side effects, highlighting the importance of monitoring for this uncommon toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib-induced polyneuropathy: A case report. Cömert, P., Albayrak, M., Yıldız, A., et al.[2021]

The combination of ibrutinib and nivolumab demonstrated an acceptable safety profile in 141 patients with relapsed or refractory B-cell malignancies, with only one dose-limiting toxicity reported, indicating that this treatment approach is generally safe for patients.

Preliminary results showed promising efficacy, with overall response rates of 61% in high-risk chronic lymphocytic leukaemia, 33% in follicular lymphoma, and 36% in diffuse large B-cell lymphoma, suggesting that this combination therapy could be effective for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. Younes, A., Brody, J., Carpio, C., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Human papillomavirus status and the relative biological effectiveness of proton radiotherapy in head and neck cancer cells. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Predictors of distant metastasis in human papillomavirus-associated oropharyngeal cancer. [2018]

3. Kuwait pubmed.ncbi.nlm.nih.gov

Impact of HPV on the Pathobiology of Cancers. [2019]

4. Greece pubmed.ncbi.nlm.nih.gov

Effect of radiation on cell proliferation and tumor hypoxia in HPV-positive head and neck cancer in vivo models. [2014]

5. United States pubmed.ncbi.nlm.nih.gov

Variations in HPV function are associated with survival in squamous cell carcinoma. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Acute and late side effects to salivary glands and oral mucosa after head and neck radiotherapy in children and adolescents. Results of the "Registry for the evaluation of side effects after radiotherapy in childhood and adolescence". [2015]

8. England pubmed.ncbi.nlm.nih.gov

Adverse event potentially due to an interaction between ibrutinib and verapamil: a case report. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Ibrutinib-induced polyneuropathy: A case report. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. [2021]