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NCT03912831

Study to Evaluate the Safety and Efficacy of KITE-439 in HLA-A*02:01+ Adults With Relapsed/Refractory HPV16+ Cancers

Terminated Phase 1 Results posted Last updated 26 December 2023
What this trial tests

Phase 1 trial testing KITE-439 in Human Papillomavirus (HPV) 16+ Relapsed/Refractory Cancer in 8 participants. Terminated before completion.

Timeline
30 April 2019
Primary endpoint
18 February 2022
18 February 2022

Quick facts

Lead sponsorGilead Sciences
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment8
Start date30 April 2019
Primary completion18 February 2022
Estimated completion18 February 2022
Sites9 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

18 and older, any sex, with Human Papillomavirus (HPV) 16+ Relapsed/Refractory Cancer. 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.

Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs) Primary · First infusion date of KITE-439 up to 21 days

A DLT is defined as protocol-defined KITE-439 related Grade 3 events with onset within the first 21 days following KITE-439 infusion and which do not resolve to ≤Grade 2 events within 48 hours, ≥Grade 4 events with onset within the first 21 days following KITE-439 infusion, regardless of duration.

GroupValue95% CI
Phase 1A: 1 x 10^6 KITE-439 (Cohort 1)0
Phase 1A: 3 x 10^6 KITE-439 (Cohort 2)0
Phase 1A: 1 x 10^7 KITE-439 (Cohort 3)0
Phase 1A: 3 x 10^7 KITE-439 (Cohort 4)0
Phase 1A: 1 x 10^8 KITE-439 (Cohort 5)0
Phase 1A: 1 x 10^8 KITE-439 (Cohort 6)0

Adverse events — posted to ClinicalTrials.gov

Time frame: All-Cause Mortality: Enrollment up to last follow-up visit date of 18 February 2022 (maximum 1.4 years); Adverse Events: First infusion date of KITE-439 up to data cut-off date of 14 February 2022 (maximum 1.4 years).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1A: 1 x 10^6 KITE-439 (Cohort 1)
Serious: 1/1 (100%)
Deaths: 1/1
Phase 1A: 3 x 10^6 KITE-439 (Cohort 2)
Serious: 0/1 (0%)
Deaths: 1/1
Phase 1A: 1 x 10^7 KITE-439 (Cohort 3)
Serious: 1/1 (100%)
Deaths: 1/1
Phase 1A: 3 x 10^7 KITE-439 (Cohort 4)
Serious: 1/1 (100%)
Deaths: 1/1
Phase 1A: 1 x 10^8 KITE-439 (Cohort 5)
Serious: 2/3 (67%)
Deaths: 3/3
Phase 1A: 1 x 10^8 KITE-439 (Cohort 6)
Serious: 0/1 (0%)
Deaths: 1/1

Serious adverse events (10 terms)

ReactionSystemPhase 1A: 1 x 10^6 KITE-43…Phase 1A: 3 x 10^6 KITE-43…Phase 1A: 1 x 10^7 KITE-43…Phase 1A: 3 x 10^7 KITE-43…Phase 1A: 1 x 10^8 KITE-43…Phase 1A: 1 x 10^8 KITE-43…
Atrial flutterCardiac disorders
Non-cardiac chest painGeneral disorders
PneumoniaInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PresyncopeNervous system disorders
SyncopeNervous system disorders
Confusional statePsychiatric disorders
HypotensionVascular disorders
Other adverse events (75 terms — click to expand)

ReactionSystemPhase 1A: 1 x 10^6 KITE-43…Phase 1A: 3 x 10^6 KITE-43…Phase 1A: 1 x 10^7 KITE-43…Phase 1A: 3 x 10^7 KITE-43…Phase 1A: 1 x 10^8 KITE-43…Phase 1A: 1 x 10^8 KITE-43…
NauseaGastrointestinal disorders
FatigueGeneral disorders
PyrexiaGeneral disorders
Neutrophil count decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
HypotensionVascular disorders
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
LeukocytosisBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Atrial flutterCardiac disorders
Sinus tachycardiaCardiac disorders
Ear painEar and labyrinth disorders
Visual impairmentEye disorders
Anal incontinenceGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Dry mouthGastrointestinal disorders
VomitingGastrointestinal disorders
ChillsGeneral disorders
Face oedemaGeneral disorders
Generalised oedemaGeneral disorders
MalaiseGeneral disorders
Mucosal drynessGeneral disorders
Oedema peripheralGeneral disorders
PainGeneral disorders
Peripheral swellingGeneral disorders
HypertransaminasaemiaHepatobiliary disorders
CellulitisInfections and infestations
PneumoniaInfections and infestations
Skin infectionInfections and infestations
FallInjury, poisoning and procedural complications
Post procedural haemorrhageInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Blood creatinine increasedInvestigations
Heart rate increasedInvestigations
International normalised ratio increasedInvestigations

Most-reported serious reactions: Atrial flutter, Non-cardiac chest pain, Pneumonia, Decreased appetite, Muscular weakness, Squamous cell carcinoma, Presyncope, Syncope.

Data from ClinicalTrials.gov NCT03912831 adverse events section.

Sponsor's own description

This study has 2 parts: Phase 1A and Phase 1B. The primary objectives of Phase 1A are to evaluate the safety of KITE-439 and to determine a recommended Phase 1B dose. The primary objective of Phase 1B is to estimate the efficacy of KITE-439 in adults who are human leukocyte antigen (HLA)-A\*02:01+ and have relapsed/refractory human papillomavirus (HPV)16+ cancers.

Publications & conference data

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

  1. Adoptive cellular therapy in solid tumor malignancies: review of the literature and challenges ahead.
    Kirtane K, Elmariah H, Chung CH, Abate-Daga D. · · 2021 · cited 146× · PMID 34301811 · DOI 10.1136/jitc-2021-002723
  2. T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors.
    Tsimberidou AM, Van Morris K, Vo HH, Eck S, et al · · 2021 · cited 119× · PMID 34193217 · DOI 10.1186/s13045-021-01115-0
  3. Engineered TCR-T Cell Immunotherapy in Anticancer Precision Medicine: Pros and Cons.
    Zhao Q, Jiang Y, Xiang S, Kaboli PJ, et al · · 2021 · cited 97× · PMID 33859650 · DOI 10.3389/fimmu.2021.658753
  4. Recent Advances and Future Directions in Clinical Management of Head and Neck Squamous Cell Carcinoma.
    Muzaffar J, Bari S, Kirtane K, Chung CH. · · 2021 · cited 97× · PMID 33477635 · DOI 10.3390/cancers13020338
  5. Novel Systemic Treatment Modalities Including Immunotherapy and Molecular Targeted Therapy for Recurrent and Metastatic Head and Neck Squamous Cell Carcinoma.
    Ghosh S, Shah PA, Johnson FM. · · 2022 · cited 47× · PMID 35887235 · DOI 10.3390/ijms23147889
  6. Immune deserts in head and neck squamous cell carcinoma: A review of challenges and opportunities for modulating the tumor immune microenvironment.
    Farlow JL, Brenner JC, Lei YL, Chinn SB. · · 2021 · cited 34× · PMID 34218062 · DOI 10.1016/j.oraloncology.2021.105420
  7. Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond.
    Zhou Z, Wang J, Wang J, Yang S, et al · · 2024 · cited 30× · PMID 38918817 · DOI 10.1186/s12943-024-02047-2
  8. The Anticancer Potential of T Cell Receptor-Engineered T Cells.
    Ecsedi M, McAfee MS, Chapuis AG. · · 2021 · cited 27× · PMID 32988787 · DOI 10.1016/j.trecan.2020.09.002

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