A Phase I/II Study of TheraT® Vector(s) Expressing Human Papillomavirus 16 Positive (HPV 16+) Specific Antigens in Patients With HPV 16+ Confirmed Cancers

Study Identifier:
H-200-001
CT.gov Identifier:
NCT04180215
EudraCT Identifier:
2019-000907-34
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
Study Complete

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Study Summary

To evaluate the safety and efficacy of HB-201 in patients with human papilloma virus-positive head and neck cancer

To Validate Intravenous And Intratumoral Applications In HPV+ Tumors

Phase I Dose Escalation: To determine a safe recommended Phase II dose (RP2D) of HB-201 for intravenous (IV) and intratumoral (IT) treatment.

Phase II Dose Expansion: To characterize safety, tolerability, antitumor activity, and immunogenicity of HB-201 in a larger cohort at 1 dose level.

To evaluate safety and efficacy of HB-201 alone but also HB-201 in combination with HB-202 as an alternating two-vector therapy.

To evaluate effect of HB-201 monotherapy and HB-201 & HB-202 combination therapy in patients with HPV 16+ confirmed cancers.

To evaluate different dose levels and dosing schedules of HB-201 as a single-vector therapy or as an alternating two-vector therapy together with HB-202

Safety, tolerability, and preliminary anti-tumour activity by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or immune RECIST were evaluated, as well as immunogenicity and pharmacodynamic biomarkers in blood and tumour tissue samples.

To determine RP2D for further exploration alone or in combination with pembrolizumab. Safety, tolerability, immunogenicity, and preliminary antitumor activity by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or immune RECIST were assessed to determine RP2D.

Two dose levels of HB-200 were explored. Safety, immunogenicity and preliminary antitumor activity were assessed.

To report long-term circulating tumor specific immune responses and clinical benefit in these patients.

HPV16 specific T cell responses were evaluated in peripheral blood mononuclear cells (PBMCs) by both direct IFN-γ ELISpot and intracellular cytokine staining (ICS) performed without prior in vitro expansion. Tumor analyses including sequencing were performed for patients with available baseline and on-treatment biopsies. Antitumor activity was measured by RECIST v1.1 per investigator assessment.

To report further updated results in 1L patients with CPS ≥20.

Safety, T-cell response, and preliminary clinical activity were assessed.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Unmapped
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
Drug: This trial is enrolling patients who have HPV16+ cancers of any type and have received prior therapy in the metastatic/recurrent setting.
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Drug: In Group B and Group E, the trial also enrolls patients with metastatic/recurrent head and neck cancer who have not yet received treatment in this setting (1L, first line) and who are eligible to receive pembrolizumab as part of their standard of care. Patients in this group will receive the study drugs in addition to their pembrolizumab standard of care regimen.
Drug: Experimental: Ph I, Group 1 and Group 2
Drug: Experimental: Ph I, Group 3 and Group 4
Drug: Experimental: Ph II, Group B
Drug: Experimental: Ph II, Group E
Drug: Experimental: Ph II, Group F
Drug: Experimental: Ph I, sub-study
Drug: Participants receive HB-201/HB-202 intravenously or, for patients with an accessible lesion, the first dose can be delivered via intratumoral injection followed by intravenous dosing.
Drug: Experimental: Ph I, Group 5
Drug: A run-in with HB-201 1-vector plus pembrolizumab was conducted prior to initiation of HB-200 plus pembrolizumab. HB-200 was administered intravenously (every 3 weeks [Q3W] then Q6W) in combination with pembrolizumab (200 mg Q3W or 400 mg Q6W, as indicated).
Drug: Patients were treated with HB-200 monotherapy (alternating intravenous administration of HB-202 and HB-201 every 3 weeks [Q3W] then Q6W) until disease progression or unacceptable toxicity. Four dose levels of HB-200 were explored.
Drug: Participants received intravenous eseba-vec (every 3 weeks [Q3W] for the first 5 doses, then Q6W for the sixth dose and onward) in combination with pembrolizumab (200 mg Q3W or 400 mg Q6W). Two dose levels were explored.
Study Status
Indicates the current recruitment status or the expanded access status
Study Complete

Requirements information
Inclusion criteria
  • Inclusion Criteria
  • All Patients:
  • Documentation of confirmed HPV 16+ cancer via genotype testing.
  • ≥ 1 measurable lesion by imaging for tumor response following RECIST
  • ECOG performance status of 0 to 1.
  • Prior curative radiation therapy and prior focal palliative completed per protocol-specified wash-out windows.
  • Screening laboratory values must meet protocol-specified criteria.
  • Able to provide tumor tissue following last treatment, unless otherwise agreed.
  • Treatment Group E or Group F:
  • Documentation of confirmed head and neck squamous cell carcinoma.
  • Eligible to receive pembrolizumab, per standard of care and product label.
  • Group E: this group includes first line / 1L patients who have not yet received treatment in the metastatic/recurrent setting.
  • Group F: Tumor progression or recurrence on standard of care therapy, including ≥1 systemic therapy.
  • Imaging Sub-Study (for specific participants at Memorial Sloan Kettering Cancer Center only):
  • Meeting requirements of inclusion criteria for Treatment Group 1 or Group 3.
  • At least 1 non-irradiated measurable lesion documented through imaging.
Exclusion criteria
  • Exclusion Criteria:
  • All patients:
  • Metastatic central nervous system disease, and/or carcinomatous meningitis.
  • Any serious or uncontrolled medical disorder that, in the opinion of the Investigator, may increase the risk associated with study participation / treatment administration.
  • Concurrent malignancy that is clinically significant or requires active intervention, unless protocol-defined criteria are met.
  • Active, known or suspected, autoimmune or inflammatory disorders requiring immunosuppressive therapy.
  • Has a life expectancy of less than 3 months.
  • Any toxicities attributed to systemic prior anticancer therapy o that have not resolved to Grade 1 or baseline prior to the first administration of study drug, unless protocol-defined criteria is met.
  • Not meeting the protocol-specified washout periods for prohibited medications.
  • Prior anaphylactic reaction to or known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
  • Positive hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibody, indicating acute or chronic infection.
  • Known history of acquired immunodeficiency syndrome.
  • For patients in Groups E or F and certain backfill cohorts:
  • History of severe hypersensitivity reaction to or other contraindication to receiving pembrolizumab.
  • History of/Presently having non-infectious pneumonitis requiring treatment.
  • Was discontinued due to a Grade 3 or higher immune-related AE (irAE) after receiving prior therapy with check point inhibitors.
  • Imaging Sub-Study (for specific participants at Memorial Sloan Kettering Cancer Center only):
  • Having splenic disorders or prior splenectomy, and can compromise protocol objectives per Investigator and/or Sponsor.
  • Meeting requirements of exclusion criteria for Treatment Group 3

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Emiliano Calvo
Status
Terminated/Withdrawn
Condition(s) Treated at Site
Unmapped