Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies
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|ClinicalTrials.gov Identifier: NCT04287868|
Recruitment Status : Not yet recruiting
First Posted : February 27, 2020
Last Update Posted : April 7, 2020
More than 30,000 cases of human papillomavirus (HPV) associated cancers occur annually in the United States. When these cancers spread, they do not respond well to standard treatments and are often incurable. Researchers want to see if a mix of drugs can help.
To learn if a mix of immunotherapy drugs can shrink tumors in people with HPV associated cancers.
People ages 18 and older with locally advanced or metastatic HPV associated cancer, such as cervical cancers; P16+ oropharyngeal cancers; anal cancers; vulvar, vaginal, penile, and squamous cell rectal cancers; or other locally advanced or metastatic solid tumors (e.g., lung, esophagus) that are known HPV+ cancers
Participants will be screened with:
- medical history
- disease confirmation (or tumor biopsy)
- physical exam
- body scans (CT, MRI, and/or nuclear)
- blood tests
- electrocardiogram (to measure the electrical activity of the heart)
- urine tests.
Participants will get PDS0101 injected under the skin every 4 weeks for 6 doses. Then they will get it every 3 months for 2 doses.
Participants will get M7824 by intravenous infusion every 2 weeks. For this, a needle is inserted into a vein. The drug is given over a 1-hour period.
Participants will get NHS-IL12 injected under the skin every 4 weeks.
Participants will get the study drugs for up to 1 year. They will visit the NIH every 2 weeks. They will repeat the screening tests during the study.
About 28 days after treatment ends, participants will have a follow-up visit or telephone call. Then they will be contacted every 3 months for 1 year, and then every 6 months after that, for the rest of their life....
|Condition or disease||Intervention/treatment||Phase|
|Cervical Cancer HPV Cancers Anal Cancer Oropharyngeal Cancer Vulvar, Vaginal, Penile, Rectal Cancer||Biological: PDS0101 Biological: M7824 Biological: NHS-IL12||Phase 1 Phase 2|
- Metastatic or refractory/recurrent HPV associated malignancies (cervical, anal, oropharyngeal cancers etc.) are poorly palliated by standard therapies. There is an unmet need for active treatments for these tumors.
- In a phase I trial of M7824 (NCT02517398) 15 out of 43 (34.9%) patients with HPV associated malignancies had radiographic tumor responses according to RECIST 1.1 or iRECIST.
- While the response rate observed with M7824 appears to be higher than single agent PD-1 inhibitors alone (15-20%), the majority of patients with these diseases still do not seem to benefit from immunotherapy.
Preclinical studies suggest that the use of a combination of multiple immunotherapy agents may have improved anti-tumor efficacy.
- Specifically, preclinical studies have shown that the combination of three immunotherapy agents (1) a therapeutic vaccine against HPV positive cancers (PDS0101), (2) a bifunctional fusion protein targeting PD-L1 and TGF beta (M7824), and (3) a tumor targeted immunocytokine (NHS-IL12) produces greater anti-tumor activity than any single or dual combination of these agents.
- To evaluate the objective response rate (ORR) according to Response Evaluation Criteria (RECIST 1.1) of the combination of (1) a therapeutic vaccine against HPV positive cancers (PDS0101), (2) a tumor targeted immunocytokine (NHS-IL12) and (3) a bifunctional fusion protein targeting PD-L1 and TGF beta (M7824) in subjects with advanced HPV associated malignancies.
- Age >= 18 years old.
Subjects with cytologically or histologically confirmed locally advanced or metastatic HPV associated malignancies:
- Cervical cancers;
- P16+ Oropharyngeal cancers;
- Anal cancers;
- Vulvar, vaginal, penile, and squamous cell rectal cancers;
- Other locally advanced or metastatic solid tumors (e.g. lung, esophagus) that are known HPV+.
- Prior first line systemic therapy is required unless the patient declines standard treatment after appropriate counseling has been provided.
- Subjects must have measurable disease.
- Prior checkpoint inhibitor use is excluded.
- This is a phase I/II trial of combination immunotherapy.
- The trial will be conducted using a Simon optimal two-stage design.
- Patients will receive HPV vaccine + NHS-IL12 + M7824.
- The first six patient will be evaluable for dose limiting toxicities (DLTs) and accrual will only continue to 8 patients if less than 2 out of the first 6 pts experience a DLT.
- If three or more out of eight patients have objective responses accrual will be expanded to enroll 20 evaluable patients.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Trial of Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies|
|Estimated Study Start Date :||April 10, 2020|
|Estimated Primary Completion Date :||July 30, 2021|
|Estimated Study Completion Date :||July 1, 2022|
Experimental: Arm 1
Triple Therapy: PDS0101 + NHS-IL12 + M7824
PDS0101 will be administered on D1, D15, D29 followed by booster vaccines every 4 weeks for up to a year. Subcutaneous 1.0ml (2.4mg of total peptide and 3 mg of R-DOTAP) injection.
M7824 will be administered at a flat dose of 1,200 mg IV (over 1 hour) once every 2 weeks.
NHS-IL12 will be administered at as dose of 16.8 (Micro)g/kg by SC injection every 4 weeks.
- Evaluate ORR of the combination of HPV vaccine, NHS-IL12, and M7824 in subjects with advanced HPV associated malignancies. [ Time Frame: One year ]Best treatment combination for patients with advanced or metastatic HPV associated malignancies.
- Safety [ Time Frame: One year ]Evaluate the safety of PDS0101, NHS-IL12, and M7824 in combination for patients with advanced or metastatic HPV associated malignancies.
- Progression-Free Survival Time [ Time Frame: Study End ]Assess progression-free survival time (PFS) according to RECIST 1.1.
- Overall Survival [ Time Frame: Study End ]Assess overall survival (OS).
- Adverse Events [ Time Frame: Study End ]To assess duration of response and ratio of patients that are hospitalized because of adverse events attributed to disease progression.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04287868
|Contact: Michell J Manu, R.N.||(240) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|Principal Investigator:||Julius Y Strauss, M.D.||National Cancer Institute (NCI)|