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Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies

Primary Purpose

Cervical Cancer, HPV Cancers, Anal Cancer

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PDS0101
M7824
NHS-IL12
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cervical Cancer focused on measuring HPV Cancers, HPV Associated Malignancies, Vaccine, Immunotherapy, Immuno-oncology

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers
  • INCLUSION CRITERIA:

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+.

Subjects must have measurable disease, per RECIST 1.1.

Subjects must have received one prior line of systemic chemotherapy as well as checkpoint therapy if checkpoint therapy is FDA approved for that specific tumor type (e.g., HNSCC and PDL1+ cervical cancer). Prior checkpoint therapy is not needed where checkpoint therapy has not been FDA approved for that specific tumor type (e.g. anal, vaginal, vulvar, penile, PDL1 negative cervical). Exceptions to the above include participant who are not eligible to receive the above therapies or who decline these standard treatment options after appropriate counseling has been provided. t.

Age >= 18 years.

ECOG performance status <= 2.

Adequate hematologic function at screening, as follows:

  • Absolute neutrophil count (ANC) >=1 x 10^9/L;
  • Hemoglobin >= 9 g/dL;
  • Platelets >=75,000/microliter.

Adequate renal and hepatic function at screening, as follows:

  • Serum creatinine <= 1.5 x upper limit of normal (ULN) OR Measured or calculated creatinine clearance >=40 mL/min for participant with creatinine levels > 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl);
  • Bilirubin <= 1.5 x ULN OR in subjects with Gilbert's syndrome, a total bilirubin <= 3.0 x ULN;
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN, unless liver metastases are present, then values must be <= 3 x ULN).

The effects of the immunotherapies on the developing human fetus are unknown. For this reason and because immunotherapeutic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for two months after study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

Participants serologically positive for HIV, Hep B, Hep C are eligible as long as the viral loads are undetectable by quantitative PCR. HIV positive participants must have CD4 count >= 200 cells per cubic millimeter at enrollment, be on stable antiretroviral therapy for at least 4 weeks and have no reported opportunistic infections or castleman s disease within 12 months prior to enrollment.

Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

Participants with prior investigational drug, chemotherapy, immunotherapy or any prior radiotherapy (except for palliative bone directed therapy) within the past 28 days prior to the first drug administration except if the investigator has assessed that all residual treatment-related toxicities have resolved or are minimal and feel the participant is otherwise suitable for enrollment. Partaicipants may continue adjuvant hormonal therapy in the setting of a definitively treated cancer (e.g. breast cancer).

Known intolerance to or life threatening side effects resulting from prior checkpoint inhibitor therapy.

Major surgery within 28 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted).

Known active brain or central nervous system metastasis (less than a month out from definitive radiotherapy or surgery), seizures requiring anticonvulsant treatment (<3 months) or clinically significant cerebrovascular accident (<3 months). In order to be eligible participant must have repeat CNS imaging at least a month after definitive treatment showing stable CNS disease. Participants with evidence of intratumoral or peritumoral hemorrhage on baseline imaging are also excluded unless the hemorrhage is grade <= 1 and has been shown to be stable on two consecutive imaging scans.

Pregnant women are excluded from this study because these drugs have not been tested in pregnant women and there is potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these immunotherapies, breastfeeding should be discontinued if the mother is treated on this protocol.

Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent with exception of:

  • Diabetes type I, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease or other mild autoimmune disorders not requiring immunosuppressive treatment;
  • Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses <= 10 mg of prednisone or equivalent per day;
  • Administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable;
  • Subjects on systemic intravenous or oral corticosteroid therapy with the exception of physiologic doses of corticosteroids (<= the equivalent of prednisone 10 mg/day) or other immunosuppressives such as azathioprine or cyclosporin A are excluded on the basis of potential immune suppression. For these subjects these excluded treatments must be discontinued at least 1 weeks prior to enrollment for recent short course use (<= 14 days) or discontinued at least 4 weeks prior to enrollment for long term use (> 14 days). In addition, the use of corticosteroids as premedication for contrast- enhanced studies is allowed prior to enrollment and on study.

Subjects with a history of serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, bleeding diathesis or recent (within 3 months) clinically significant bleeding events, or other illness considered by the Investigator as high risk for investigational drug treatment.

Subjects unwilling to accept blood products as medically indicated.

History of non-HPV associated second malignancy within 3 years of enrollment except localized malignancy which has been adequately treated or malignancy which does not require active systemic treatment (e.g,, low risk CCL). Patients taking adjuvant hormonal therapy for definitively treated cancers (e.g. breast cancer) are eligible.

Subjects with a known severe hypersensitivity reaction to a monoclonal antibodies (grade >/= 3 NCI-CTCAE v5) will be evaluated by the allergy/immunology team prior to enrollment.

Receipt of prior lymphodepleting chemotherapy (e.g. cyclophosphamide, fludarabine) or any organ transplantation requiring ongoing immunosuppression.

Sites / Locations

  • National Institutes of Health Clinical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1

Arm 2

Arm Description

Triple Therapy: PDS0101 + NHS-IL12 + M7824 (MSB0011395C); The dose level of NHS-IL12 may decrease depending on dose limiting toxicity (DLT) events. The dose level of human papillomavirus vaccine (HVP) vaccine and M7824 will remain constant.

Triple Therapy: PDS0101 + NHS-IL12 + M7824 (MSB0011395C); Accrual will be expanded first to 8 participants and then to 20 evaluable participants at the dose level selected in Arm 1 if more than 3 of 8 participants have an objective response. Triple Therapy: PDS0101 + NHS-IL12 + M7824; Reduced doses.

Outcomes

Primary Outcome Measures

Evaluate ORR of the combination of HPV vaccine, NHS-IL12, and M7824 in subjects with advanced HPV associated malignancies.
Best treatment combination for participants with advanced or metastatic HPV associated malignancies.

Secondary Outcome Measures

Safety
Evaluate the safety of PDS0101, NHS-IL12, and M7824 in combination for participants with advanced or metastatic HPV associated malignancies.
Progression-Free Survival Time
Assess progression-free survival time (PFS) according to RECIST 1.1.
Overall Survival
Assess overall survival (OS).
Adverse Events
To assess duration of response and ratio of participants that are hospitalized because of adverse events attributed to disease progression.
Safety of reduced dose level in specific cervical cancer patients
Determine safety of reduced dose level in cervical cancer patients with prior pelvic radiation and boost brachytherapy where a potential higher risk of grade 3 hematuria may exist with the full starting doses of the study drugs.

Full Information

First Posted
February 26, 2020
Last Updated
July 24, 2023
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04287868
Brief Title
Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies
Official Title
Phase I/II Trial of Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
July 10, 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 9, 2020 (Actual)
Primary Completion Date
July 26, 2022 (Actual)
Study Completion Date
July 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Background: 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. Objective: To learn if a mix of immunotherapy drugs can shrink tumors in people with HPV associated cancers. Eligibility: People ages 18 and older with locally advanced or metastatic HPV associated cancer, such as cervical cancers; cyclin-dependent kinase inhibitor 2A (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 Design: Participants will be screened with: medical history disease confirmation (or tumor biopsy) physical exam body scans (computed tomography (CT), magnetic resonance imaging (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 (MSB0011395C) 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. Patients with cervical cancer with prior pelvic radiation and boost brachytherapy will be enrolled in a separate cohort to evaluate safety and preliminary evidence of efficacy...
Detailed Description
Background: 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 (MSB0011395C) (NCT02517398) 15 out of 43 (34.9%) participants with HPV associated malignancies had radiographic tumor responses according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Immune Response Evaluation Criteria in Solid Tumors (iRECIST). While the response rate observed with M7824 appears to be higher than single agent programmed cell death protein 1 (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 human papilloma virus (HPV) positive cancers (PDS0101), (2) a bifunctional fusion protein targeting programmed death-ligand 1 (PD-L1) and transforming growth factor (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. Objective: 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 checkpoint naive advanced HPV associated malignancies. Eligibility: 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 participant declines standard treatment after appropriate counseling has been provided. Subjects must have measurable disease. Design: This is a phase I/II trial of combination immunotherapy. The trial will be conducted using a Simon optimal two-stage design. Participants will receive HPV vaccine + NHS-IL12 + M7824. The first six participants will be evaluable for dose limiting toxicities (DLTs) and accrual will only continue to 8 participants who have not been treated with checkpoint inhibitors if less than 2 out of the first 6 participants experience a DLT. If three or more out of eight participants who have not been treated with checkpoint inhibitors have objective responses accrual will be expanded to enroll 20 evaluable participants. Patients with cervical cancer with prior pelvic radiation and boost brachytherapy will be enrolled in a separate cohort to evaluate safety and preliminary evidence of efficacy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer, HPV Cancers, Anal Cancer, Oropharyngeal Cancer, Vulvar, Vaginal, Penile, Rectal Cancer
Keywords
HPV Cancers, HPV Associated Malignancies, Vaccine, Immunotherapy, Immuno-oncology

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
Triple Therapy: PDS0101 + NHS-IL12 + M7824 (MSB0011395C); The dose level of NHS-IL12 may decrease depending on dose limiting toxicity (DLT) events. The dose level of human papillomavirus vaccine (HVP) vaccine and M7824 will remain constant.
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
Triple Therapy: PDS0101 + NHS-IL12 + M7824 (MSB0011395C); Accrual will be expanded first to 8 participants and then to 20 evaluable participants at the dose level selected in Arm 1 if more than 3 of 8 participants have an objective response. Triple Therapy: PDS0101 + NHS-IL12 + M7824; Reduced doses.
Intervention Type
Biological
Intervention Name(s)
PDS0101
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
M7824
Intervention Description
M7824 will be administered at a flat dose of 1,200 mg IV (over 1 hour) once every 2 weeks.
Intervention Type
Biological
Intervention Name(s)
NHS-IL12
Intervention Description
NHS-IL12 will be administered at as dose of potentially de-escalating doses by SC injection every 4 weeks.
Primary Outcome Measure Information:
Title
Evaluate ORR of the combination of HPV vaccine, NHS-IL12, and M7824 in subjects with advanced HPV associated malignancies.
Description
Best treatment combination for participants with advanced or metastatic HPV associated malignancies.
Time Frame
one year
Secondary Outcome Measure Information:
Title
Safety
Description
Evaluate the safety of PDS0101, NHS-IL12, and M7824 in combination for participants with advanced or metastatic HPV associated malignancies.
Time Frame
One year
Title
Progression-Free Survival Time
Description
Assess progression-free survival time (PFS) according to RECIST 1.1.
Time Frame
Study End
Title
Overall Survival
Description
Assess overall survival (OS).
Time Frame
Study End
Title
Adverse Events
Description
To assess duration of response and ratio of participants that are hospitalized because of adverse events attributed to disease progression.
Time Frame
Study End
Title
Safety of reduced dose level in specific cervical cancer patients
Description
Determine safety of reduced dose level in cervical cancer patients with prior pelvic radiation and boost brachytherapy where a potential higher risk of grade 3 hematuria may exist with the full starting doses of the study drugs.
Time Frame
One year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Subjects with cytologically or histologically confirmed locally advanced or metastatic human papilloma virus (HPV) associated malignancies: Cervical cancers; cyclin-dependent kinase inhibitor 2A (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+. Subjects must have measurable disease, per response evaluation criteria in solid tumors (RECIST) 1.1. Subjects must have received one prior line of systemic chemotherapy as well as checkpoint therapy if checkpoint therapy is Food and Drug Administration (FDA) approved for that specific tumor type (e.g., head and neck squamous cell carcinoma (HNSCC) and programmed death-ligand 1 (PDL1+) cervical cancer). Prior checkpoint therapy is not needed where checkpoint therapy has not been FDA approved for that specific tumor type (e.g., anal, vaginal, vulvar, penile, PDL1 negative cervical). Exceptions to the above include participant who are not eligible to receive the above therapies or who decline these standard treatment options after appropriate counseling has been provided. Age >= 18 years. Eastern Cooperative Oncology Group (ECOG) performance status <= 2. Adequate hematologic function at screening, as follows: Absolute neutrophil count (ANC) >=1 x 10^9/L; Hemoglobin >= 9 g/dL; Platelets >=75,000/microliter. Adequate renal and hepatic function at screening, as follows: Serum creatinine <= 1.5 x upper limit of normal (ULN) OR Measured or calculated creatinine clearance >=40 mL/min for participant with creatinine levels > 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl); Bilirubin <= 1.5 x ULN OR in subjects with Gilbert's syndrome, a total bilirubin <= 3.0 x ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN, unless liver metastases are present, then values must be <= 3 x ULN). The effects of the immunotherapies on the developing human fetus are unknown. For this reason and because immunotherapeutic agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use highly effective contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for two months after study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Participants serologically positive for human immunodeficiency virus (HIV), hepatitis (Hep) B, Hep C are eligible as long as the viral loads are undetectable by quantitative polymerase chain reaction (PCR). HIV positive participants must have clusters of differentiation 4 (CD4) count >= 200 cells per cubic millimeter at enrollment, be on stable antiretroviral therapy for at least 4 weeks and have no reported opportunistic infections or Castleman's disease within 12 months prior to enrollment. Ability of subject to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: Participants with prior investigational drug, chemotherapy, immunotherapy or any prior radiotherapy (except for palliative bone directed therapy) within the past 28 days prior to the first drug administration except if the investigator has assessed that all residual treatment-related toxicities have resolved or are minimal and feel the participant is otherwise suitable for enrollment. Participants may continue adjuvant hormonal therapy in the setting of a definitively treated cancer (e.g., breast cancer). Known intolerance to or life-threatening side effects resulting from prior checkpoint inhibitor therapy. Major surgery within 28 days prior to the first drug administration (minimally invasive procedures such as diagnostic biopsies are permitted). Known active brain or central nervous system metastasis (less than a month out from definitive radiotherapy or surgery), seizures requiring anticonvulsant treatment (<3 months) or clinically significant cerebrovascular accident (<3 months). In order to be eligible participant must have repeat central nervous system (CNS) imaging at least a month after definitive treatment showing stable CNS disease. Participants with evidence of intra-tumoral or peritumoral hemorrhage on baseline imaging are also excluded unless the hemorrhage is grade <= 1 and has been shown to be stable on two consecutive imaging scans. Pregnant women are excluded from this study because these drugs have not been tested in pregnant women and there is potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these immunotherapies, breastfeeding should be discontinued if the mother is treated on this protocol. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent with exception of: Diabetes type I, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease or other mild autoimmune disorders not requiring immunosuppressive treatment; Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses <= 10 mg of prednisone or equivalent per day; Administration of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable; Subjects on systemic intravenous or oral corticosteroid therapy with the exception of physiologic doses of corticosteroids (<= the equivalent of prednisone 10 mg/day) or other immunosuppressives such as azathioprine or cyclosporin A are excluded on the basis of potential immune suppression. For these subjects these excluded treatments must be discontinued at least 1 weeks prior to enrollment for recent short course use (<= 14 days) or discontinued at least 4 weeks prior to enrollment for long term use (> 14 days). In addition, the use of corticosteroids as premedication for contrast- enhanced studies is allowed prior to enrollment and on study. Subjects with a history of serious intercurrent chronic or acute illness, such as cardiac or pulmonary disease, hepatic disease, bleeding diathesis or recent (within 3 months) clinically significant bleeding events, or other illness considered by the Investigator as high risk for investigational drug treatment. Subjects unwilling to accept blood products as medically indicated. History of non-HPV associated second malignancy within 3 years of enrollment except localized malignancy which has been adequately treated or malignancy which does not require active systemic treatment (e.g., low risk chronic lymphocytic leukemia (CCL). Patients taking adjuvant hormonal therapy for definitively treated cancers (e.g., breast cancer) are eligible. Subjects with a known severe hypersensitivity reaction to a monoclonal antibodies (grade >/= 3 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v5) will be evaluated by the allergy/immunology team prior to enrollment. Receipt of prior lymphodepleting chemotherapy (e.g., cyclophosphamide, fludarabine) or any organ transplantation requiring ongoing immunosuppression.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charalampos Floudas, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All individual participant data (IPD)recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP). All collected IPD will be shared with collaborators under the terms of collaborative agreements.
IPD Sharing Time Frame
Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
IPD Sharing Access Criteria
Clinical data will be made available via subscription to the Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2020-C-0045.html
Description
NIH Clinical Center Detailed Web Page

Learn more about this trial

Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies

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