The combination of an immunotherapy such as pembrolizumab and radiation therapy given before surgery is known as neoadjuvant immunoradiotherapy (NIRT), and it may help shrink cancer prior to surgery, minimize the radiation and surgery-induced side effects or prevent cancer from coming back after surgery. The possibility that patients with head and neck cancer who receive this treatment could forego lengthy post-operative chemoradiation and a host of side effects is a paradigm shift in treatment approach.
This month we re-introduce an investigator-initiated clinical trial study sponsored by the Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon, that will evaluate the safety and efficacy of the immunotherapy pembrolizumab and stereotactic body radiation therapy (SBRT) in reducing the size or eradicating tumors prior to surgery in patients with head and neck squamous cell carcinoma.
Pembrolizumab is used to treat many types of cancer by blocking the PD-1 pathway and helping T cells find and attack cancer cells. In this phase II study, patients also receive a three-day course of SBRT, which focuses a high-dose radiation beam on the tumor, minimizing damage to normal healthy tissue.
Encouraging findings from recent studies suggest immunotherapy and SBRT may be a viable option for head and neck cancer patients in the near future. In fact, in an earlier NIRT study, also sponsored by the Earle A. Chiles Research Institute, patients with HPV-positive and HPV-negative head and neck cancers received neoadjuvant treatment using immunotherapy nivolumab with radiotherapy. The results, which were published in the Journal for ImmunoTherapy of Cancer, showed the combination of nivolumab and radiotherapy were safe and effective in reducing the size of tumor in 90% of the patients treated. Among the entire study group, the major pathologic response was 86%, and the pathologic complete response (no sign of cancer) was 67%. As a result, only one patient needed radiation or chemotherapy after surgery.
R. Bryan Bell, M.D., D.D.S., FACS, FRCS(Ed), medical director of Providence Head and Neck Cancer Program and Clinic, is the principal investigator of this phase II NIRT study. Providence is the only location in the world currently recruiting patients.
Learn more about the study:
Neoadjuvant Immunoradiotherapy in Head & Neck Cancer (NIRT 2-HNC)
Two studies evaluate new therapies for breast cancer with brain metastasis
The brain can be a site where breast cancer metastasizes, often occurring after the cancer has spread to other organs, such as the lungs, liver or bones. Brain metastasis is a challenge to treat because of the brain-blood barrier, a network of impermeable blood vessels and tissue that helps protect the brain from most compounds – including chemotherapeutic agents.
Currently, Providence Cancer Institute has two clinical trials open for patients with breast cancer that has metastasized in the brain. One study will evaluate tucatinib, a Her-2-neu specific tyrosine kinase-inhibitor, with standard of care treatment trastuzumab/pertuzumab or T-DM1 (trastuzumab/emtansine). The second trial is a phase I/II study evaluating the novel estrogen receptor antagonist OP-1250 in patients with HR+ and HER2- breast cancer, with or without brain metastasis.
BRIDGET: Adding tucatinib to standard of care in HER2+ breast cancer patients
This phase II study, known as BRIDGET, is open to patients with advanced human epidermal growth factor receptor 2 positive (HER2+) breast cancer with brain metastasis and stable extracranial disease. Patients must be on either first-line trastuzumab/pertuzumab, second-line T-DM1 in the metastatic setting or adjuvant trastuzumab-based therapy or T-DM1 with isolated intracranial recurrence to enroll.
- Trastuzumab is a form of targeted therapy, attaching itself to specific molecules (HER2 receptors) on the surface of tumor cells. Its presence on these receptors prevents HER2 from stimulating cancer cell growth, and helping the immune system kill cancer cells.
- Pertuzumab is a monoclonal antibody that can interfere with the growth and spread of tumor cells.
- T-DM1 is trastuzumab with emtansine, an antibody-drug conjugate (targeted therapy) given as first-line, second-line as well as later than second-line treatment of metastatic breast cancer.
Tucatinib plus trastuzumab showed promise in earlier trial
Tucatinib is a highly selective tyrosine kinase inhibitor that works by blocking the action of an abnormal protein that signals cancer cells to multiply. The medication is approved to treat adults with HER2+ cancer, including breast cancer that cannot be removed by surgery or has spread to other parts of the body.
In a phase 1b dose-escalation trial, tucatinib in combination with trastuzumab and capecitabine, a chemotherapy, showed encouraging antitumor activity in patients with HER2+ metastatic breast cancer, including those with brain metastasis.
The difference with BRIDGET, however, is the use of more targeted therapies, without chemotherapy.
Providence Cancer Institute is enrolling patients in BRIDGET. The principal investigator is Alison Conlin, M.D., MPH, medical director, Providence Breast Cancer Program and High-Risk Breast Cancer Clinic, Providence Cancer Institute.
Get the full details about this trial:
Study of OP-1250 in people with HR+ and HER2- breast cancer with brain metastases
In October 2022, we covered phase I of the study in this newsletter series, but here we focus on phase II of the study.
In phase I, the first arm (Part A, dose escalation) evaluates the safety and pharmacokinetics (PK) of a range of OP-1250 doses administered orally each day. The second arm (Part B, dose expansion) is a comprehensive review of the safety, tolerability and PK data, which determines the recommended dosage of OP-1250 in phase II.
Phase II further explores the clinical activity, safety and PK of OP-1250 at the recommended dosage and will estimate the preliminary anti-tumor activity. There are three distinct cohorts in phase II, although only one is currently enrolling patients:
- Cohort A: Closed to enrollment. (Included patients with measurable disease without evidence of brain metastases.)
- Cohort B: Closed to enrollment. (Included patients with non-measurable disease and without evidence of brain metastases.)
- Cohort C: Open to approximately 15 patients with measurable and non-measurable disease and with brain metastases.
This clinical trial is offered at sites worldwide. The principal investigator is Alison Conlin, M.D., MPH, medical director, Providence Breast Cancer Program and High-Risk Breast Cancer Clinic, Providence Cancer Institute.
Get the full trial details here:
A Phase I Dose Escalation and Dose Expansion and Phase II Monotherapy Open-label, First-in-Human, Multicenter Study of OP-1250 in Adult Subjects with Advanced and/or Metastatic Hormone Receptor (HR)-positive, HER2-negative Breast Cancer
For more information about any of these studies or to refer a patient, please contact our staff in Clinical Research:
See current and past studies at Providence Cancer Institute:
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Providence Center of Excellence for precision immuno-oncology and cellular therapy
Since 1993, cancer research has been the primary focus of the Earle A. Chiles Research Institute, the research arm of Providence Cancer Institute of Oregon. Under the leadership of Walter J. Urba, M.D., Ph.D., our team of physicians and scientists work together to improve cancer treatment methods – seamlessly joining lab research and clinical trials with medical practice.
Our main area of research is cancer immunotherapy, and with the advancements in genomic sequencing we are bringing together the power of immunotherapy and personalized medicine to accelerate leading-edge research and groundbreaking discoveries for patients with cancer.