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NCT04287868

Combination Immunotherapy in Subjects With Advanced HPV Associated Malignancies

Active, enrolled Phase 1, PHASE2 Results posted Last updated 13 April 2026
What this trial tests

Phase 1, PHASE2 trial testing PDS0101 in Cervical Cancer in 51 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
9 June 2020
Primary endpoint
26 July 2022
1 July 2026

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment51
Start date9 June 2020
Primary completion26 July 2022
Estimated completion1 July 2026
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Cervical Cancer or HPV Cancers. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Best Overall Response (BOR) in Checkpoint Naive and Immune Checkpoint Blockade (ICB) Resistant Disease in Participants With Advanced or Metastatic Human Papillomavirus (HPV) Associated Malignancies Primary · Every 2 months, up to approximately 10 months

BOR is defined as a complete response or partial response assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

Complete Response
GroupValue95% CI
All Participants4
Participants With Human Papillomavirus 16 (HPV16+) Tumors4
Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Naive2
Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Resistant2
Partial Response
GroupValue95% CI
All Participants7
Participants With Human Papillomavirus 16 (HPV16+) Tumors7
Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Naive3
Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Resistant4
Overall Response rate (CR+PR)
GroupValue95% CI
All Participants11
Participants With Human Papillomavirus 16 (HPV16+) Tumors11
Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Naive5
Human Papillomavirus 16 Tumors (HPV-16+), Immune Checkpoint Blockade (ICB) - Resistant6
Number of Participants With Grades 1, 2, 3, 4 and/or 5 Treatment Related Adverse Events Secondary · Date treatment consent signed to date off study, approximately 34 months and 20 days.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

Grade 1
GroupValue95% CI
Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies45
Grade 2
GroupValue95% CI
Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies42
Grade 3
GroupValue95% CI
Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies25
Grade 4
GroupValue95% CI
Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies1
Grade 5
GroupValue95% CI
Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies0
Ratio of Participants That Are Hospitalized Because of Adverse Events Attributed to Disease Progression. Secondary · While participant on study; an average of 3 months

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Progressive disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions.

GroupValue95% CI
Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies0.04
Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy0
Number of Treatment Related Grades 1, 2, 3, 4 and/or 5 Adverse Events Secondary · Date treatment consent signed to date off study, approximately 34 months and 20 days.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

Grade 1
GroupValue95% CI
Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy3
Grade 2
GroupValue95% CI
Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy3
Grade 3
GroupValue95% CI
Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy1
Grade 4
GroupValue95% CI
Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy1
Grade 5
GroupValue95% CI
Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy0
Duration of Response (DOR) Secondary · At disease progression, an average of 10 months

DOR is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that progressive disease (PD) is objectively documented and is evaluated using the Kaplan-Meier method. Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response is at least a 30% decrease in the sum of the diameters of target

GroupValue95% CI
Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies10.63.7 – NA
Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy10.2NA – NA
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) Secondary · Date treatment consent signed to date off study, approximately 34 months and 20 days.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent

GroupValue95% CI
Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies47
Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy3

Adverse events — posted to ClinicalTrials.gov

Time frame: Date treatment consent signed to date off study, approximately 34 months and 20 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1, Arm 1: Human Papillomavirus (HPV) Associated Malignancies
Serious: 18/47 (38%)
Deaths: 28/47
Cohort 2, Arm 2: Cervical Cancer With Prior Pelvic Radiation and Boost Brachytherapy
Serious: 1/3 (33%)
Deaths: 0/3

Serious adverse events (34 terms)

ReactionSystemCohort 1, Arm 1: Human Pap…Cohort 2, Arm 2: Cervical …
Abdominal painGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
General disorders and administration site conditions - Other, Mucosal bleedingGeneral disorders
HematuriaRenal and urinary disorders
Lung infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Alkaline phosphatase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
BacteremiaInfections and infestations
Cardiac disorders - Other, Immune mediated myocarditisCardiac disorders
Creatinine increasedInvestigations
Duodenal hemorrhageGastrointestinal disorders
Enterocolitis infectiousInfections and infestations
FeverGeneral disorders
Flu like symptomsGeneral disorders
Gastric hemorrhageGastrointestinal disorders
GastroparesisGastrointestinal disorders
General disorders and administration site conditions - Other, HematuriaGeneral disorders
General disorders and administration site conditions - Other, MUCOSAL BLEEDING, VAGINAL HEMORRHAGE;General disorders
General disorders and administration site conditions - Other, Mucosal bleeding (anal bleeding)General disorders
General disorders and administration site conditions - Other, Mucosal bleeding, vaginalGeneral disorders
General disorders and administration site conditions - Other, Mucosal bleeding-HematuriaGeneral disorders
HyperglycemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Immune system disorders - Other, Hemophagocytic LymphohistiocytosisImmune system disorders
Other adverse events (266 terms — click to expand)

ReactionSystemCohort 1, Arm 1: Human Pap…Cohort 2, Arm 2: Cervical …
Injection site reactionGeneral disorders
AnemiaBlood and lymphatic system disorders
Flu like symptomsGeneral disorders
FatigueGeneral disorders
Lymphocyte count decreasedInvestigations
PainGeneral disorders
NauseaGastrointestinal disorders
ConstipationGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
HypoalbuminemiaMetabolism and nutrition disorders
AnorexiaMetabolism and nutrition disorders
Mucositis oralGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
HeadacheNervous system disorders
PruritusSkin and subcutaneous tissue disorders
Alanine aminotransferase increasedInvestigations
Alkaline phosphatase increasedInvestigations
DehydrationMetabolism and nutrition disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Creatinine increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
DiarrheaGastrointestinal disorders
DizzinessNervous system disorders
HematuriaRenal and urinary disorders
HyponatremiaMetabolism and nutrition disorders
HypophosphatemiaMetabolism and nutrition disorders
Oral hemorrhageGastrointestinal disorders
FeverGeneral disorders
HypocalcemiaMetabolism and nutrition disorders
HypotensionVascular disorders
Abdominal painGastrointestinal disorders
Activated partial thromboplastin time prolongedInvestigations
Back painMusculoskeletal and connective tissue disorders
ChillsGeneral disorders
Lipase increasedInvestigations
Rash acneiformSkin and subcutaneous tissue disorders
Urinary tract infectionInfections and infestations
Edema limbsGeneral disorders

Most-reported serious reactions: Abdominal pain, Anemia, General disorders and administration site conditions - Other, Mucosal bleeding, Hematuria, Lung infection, Alanine aminotransferase increased, Alkaline phosphatase increased, Aspartate aminotransferase increased.

Data from ClinicalTrials.gov NCT04287868 adverse events section.

Sponsor's own description

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...

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting TGF-β signal transduction for fibrosis and cancer therapy.
    Peng D, Fu M, Wang M, Wei Y, et al · · 2022 · cited 752× · PMID 35461253 · DOI 10.1186/s12943-022-01569-x
  2. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  3. Cervical Cancer Immunotherapy: Facts and Hopes.
    Ferrall L, Lin KY, Roden RBS, Hung CF, et al · · 2021 · cited 255× · PMID 33888488 · DOI 10.1158/1078-0432.ccr-20-2833
  4. Tumor Immunity and Immunotherapy for HPV-Related Cancers.
    Shamseddine AA, Burman B, Lee NY, Zamarin D, et al · · 2021 · cited 140× · PMID 33990345 · DOI 10.1158/2159-8290.cd-20-1760
  5. Matching patients to clinical trials with large language models.
    Jin Q, Wang Z, Floudas CS, Chen F, et al · · 2024 · cited 122× · PMID 39557832 · DOI 10.1038/s41467-024-53081-z
  6. Therapeutic Vaccines for HPV-Associated Malignancies.
    Smalley Rumfield C, Roller N, Pellom ST, Schlom J, et al · · 2020 · cited 87× · PMID 33117742 · DOI 10.2147/itt.s273327
  7. Tumor microenvironment and immunotherapy of oral cancer.
    Liu C, Wang M, Zhang H, Li C, et al · · 2022 · cited 78× · PMID 36209263 · DOI 10.1186/s40001-022-00835-4
  8. Landscape of Myeloid-derived Suppressor Cell in Tumor Immunotherapy.
    Hao Z, Li R, Wang Y, Li S, et al · · 2021 · cited 72× · PMID 34689842 · DOI 10.1186/s40364-021-00333-5

Verify or expand the search:

Other trials of PDS0101

Trials testing the same drug.

Other recruiting trials for Cervical Cancer

Currently open trials in the same condition.

Other National Cancer Institute (NCI) trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04287868.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing