Human Papillomavirus (HPV) 16+ Relapsed/Refractory Cancer
Conditions
Brief summary
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.
Interventions
DRUGKITE-439
A single infusion of E7 TCR T cells (KITE-439).
DRUGCyclophosphamide
Administered intravenously.
DRUGFludarabine
Administered intravenously.
DRUGInterleukin-2
Administered subcutaneously.
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Advanced cancer defined as relapsed or refractory disease after at least 1 line of therapy that included systemic chemotherapy and that is not amenable to definitive locoregional therapy * HPV16+ tumor as confirmed by the central laboratory * HLA type is HLA-A\*02:01+ per local assessment * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Key
Exclusion criteria
* Presence of fungal, bacterial, viral, or other infection requiring anti-microbials for management * Note: Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite medical monitor * Primary immunodeficiency * History of autoimmune disease (eg, Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years prior to enrollment * Known history of infection with human immunodeficiency virus (HIV), hepatitis B (HBsAg positive), or hepatitis C (anti-HCV positive). A history of treated hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (qPCR) and/or nucleic acid testing Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs) | 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. |
| Phase 1B: Objective Response Rate (ORR) | Up to 1.4 years | ORR was defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as evaluated by modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1B: Duration of Response (DOR) | Up to 1.4 years | For participants who experience an objective response, DOR was defined as the time from the date of their first objective response to the date of disease progression per modified RECIST v1.1 or death from any cause. |
| Phase 1B: Percentage of Participants Experiencing Adverse Events | Up to 1.4 years | — |
| Phase 1B: Progression-Free Survival (PFS) | Up to 1.4 years | PFS was defined as the time from the KITE-439 infusion date to the date of disease progression per modified RECIST v1.1 or death from any cause. |
| Phase 1B: Percentage of Participants With Replication-competent Retrovirus (RCR) | Up to 1.4 years | — |
| Phase 1B: Levels of E7 TCR T Cells | Up to 1.4 years | — |
| Phase 1B: Percentage of Participants With Anti-KITE-439 Antibodies | Up to 1.4 years | — |
| Phase 1B: Overall Survival | Up to 1.4 years | Overall survival was defined as the time from KITE-439 infusion to the date of death. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States.
Pre-assignment details
8 participants were screened. The study was terminated earlier than planned, and thus the study did not proceed to Phase 1B.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1A: 1 x 10^6 KITE-439 (Cohort 1) Participants received conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^6 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | 1 |
| Phase 1A: 3 x 10^6 KITE-439 (Cohort 2) Participants received conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10\^6 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | 1 |
| Phase 1A: 1 x 10^7 KITE-439 (Cohort 3) Participants received conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | 1 |
| Phase 1A: 3 x 10^7 KITE-439 (Cohort 4) Participants received conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 3 × 10\^7 E7 TCR T cells/kg on Day 0 along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | 1 |
| Phase 1A: 1 x 10^8 KITE-439 (Cohort 5) Participants received conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose was 5 × 10\^9 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | 3 |
| Phase 1A: 1 x 10^8 KITE-439 (Cohort 6) Participants received conditioning chemotherapy of cyclophosphamide 30 mg/kg, IV infusion, once on Days -7 and -6 and fludarabine, 25 mg/m\^2, IV infusion, once on Days -7 to -3 followed by KITE-439 infusion, up to 1 × 10\^8 E7 TCR T cells/kg on Day 0 (maximum allowable dose was 1 ×10\^10 E7 TCR T cells) along with the interleukin-2 of 2,50,000 IU/kg, SC injection, once on Days 0 to 6. | 1 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 1 | 1 | 1 | 1 |
| Overall Study | Reason not Specified | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Participant | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Phase 1A: 1 x 10^6 KITE-439 (Cohort 1) | Total | Phase 1A: 1 x 10^8 KITE-439 (Cohort 6) | Phase 1A: 1 x 10^8 KITE-439 (Cohort 5) | Phase 1A: 3 x 10^7 KITE-439 (Cohort 4) | Phase 1A: 1 x 10^7 KITE-439 (Cohort 3) | Phase 1A: 3 x 10^6 KITE-439 (Cohort 2) |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.0 years | 58.5 years STANDARD_DEVIATION 11.28 | 40.0 years | 59.7 years STANDARD_DEVIATION 9.45 | 77.0 years | 60.0 years | 54.0 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 8 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 8 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 1 Participants | 8 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 5 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 3 / 3 | 1 / 1 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 | 1 / 1 | 1 / 1 | 2 / 3 | 0 / 1 |
Outcome results
Primary
Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs)
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.
Time frame: First infusion date of KITE-439 up to 21 days
Population: DLT evaluable set included participants treated in Phase 1A who received the target dose (± 20%) and had the opportunity to be followed for at least 21 days after the KITE-439 infusion or received a dose of KITE-439 lower than the target dose and experienced a DLT within 21 days after the KITE-439 infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1A: 1 x 10^6 KITE-439 (Cohort 1) | Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs) | 0 percentage of participants |
| Phase 1A: 3 x 10^6 KITE-439 (Cohort 2) | Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs) | 0 percentage of participants |
| Phase 1A: 1 x 10^7 KITE-439 (Cohort 3) | Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs) | 0 percentage of participants |
| Phase 1A: 3 x 10^7 KITE-439 (Cohort 4) | Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs) | 0 percentage of participants |
| Phase 1A: 1 x 10^8 KITE-439 (Cohort 5) | Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs) | 0 percentage of participants |
| Phase 1A: 1 x 10^8 KITE-439 (Cohort 6) | Phase 1A: Percentage of Participants Experiencing Adverse Events Defined as Dose-Limiting Toxicities (DLTs) | 0 percentage of participants |
Primary
Phase 1B: Objective Response Rate (ORR)
ORR was defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as evaluated by modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: Up to 1.4 years
Population: Due to early termination of study, Phase 1B dose of KITE-439 was not established and Phase 1B of study was not conducted.
Secondary
Phase 1B: Duration of Response (DOR)
For participants who experience an objective response, DOR was defined as the time from the date of their first objective response to the date of disease progression per modified RECIST v1.1 or death from any cause.
Time frame: Up to 1.4 years
Population: Due to early termination of study, Phase 1B dose of KITE-439 was not established and Phase 1B of study was not conducted.
Secondary
Phase 1B: Levels of E7 TCR T Cells
Time frame: Up to 1.4 years
Population: Due to early termination of study, Phase 1B dose of KITE-439 was not established and Phase 1B of study was not conducted.
Secondary
Phase 1B: Overall Survival
Overall survival was defined as the time from KITE-439 infusion to the date of death.
Time frame: Up to 1.4 years
Population: Due to early termination of study, Phase 1B dose of KITE-439 was not established and Phase 1B of study was not conducted.
Secondary
Phase 1B: Percentage of Participants Experiencing Adverse Events
Time frame: Up to 1.4 years
Population: Due to early termination of study, Phase 1B dose of KITE-439 was not established and Phase 1B of study was not conducted.
Secondary
Phase 1B: Percentage of Participants With Anti-KITE-439 Antibodies
Time frame: Up to 1.4 years
Population: Due to early termination of study, Phase 1B dose of KITE-439 was not established and Phase 1B of study was not conducted.
Secondary
Phase 1B: Percentage of Participants With Replication-competent Retrovirus (RCR)
Time frame: Up to 1.4 years
Population: Due to early termination of study, Phase 1B dose of KITE-439 was not established and Phase 1B of study was not conducted.
Secondary
Phase 1B: Progression-Free Survival (PFS)
PFS was defined as the time from the KITE-439 infusion date to the date of disease progression per modified RECIST v1.1 or death from any cause.
Time frame: Up to 1.4 years
Population: Due to early termination of study, Phase 1B dose of KITE-439 was not established and Phase 1B of study was not conducted.