Trial Outcomes & Findings for T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers (NCT NCT05035407)

Last Updated: 2025-12-02

Results Overview

The MTD is the highest dose at which \< 1 of 6 participants experienced a DLT or the highest dose level studied if 2 DLTs are not observed at any of the dose levels. A DLT is all grade 3 and greater toxicities related to cell infusion, with the exception of: Cytokine Release Syndrome (CRS) that resolves \< grade 2 within 14 days of the last dose of aldesleukin; Autoimmune toxicity that resolves \< grade 2 within 14 days from starting symptoms treatment (e.g. steroids); Cardiac, gastrointestinal, dermatological, hepatic, pulmonary, renal, hematologic, neurologic toxicity, or toxicity specified in the protocol attributable to aldesleukin that resolves to grade 2 within 14 days of the last dose of aldesleukin; and Transient grade 3 hypoxia associated with cell infusion that corrects to \< grade 2 with supplemental oxygen and/or that resolves to \< grade 2 within 24 hours; and Hemorrhage due to underlying cancer or prior radiotherapy.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

36 participants

Primary outcome timeframe

3 months

Results posted on

2025-12-02

Participant Flow

Participant milestones

Participant milestones
Measure	1 x 10^8 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 1 x 10\^8 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2).	5 x 10^8 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 5 x 10\^8 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2). No participants were enrolled at this dose level.	1 x 10^9 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 1 x 10\^9 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2). No participants were enrolled at this dose level.	5 x 10^9 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 5 x 10\^9 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2). No participants were enrolled at this dose level.	1 x 10^10 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 1 x 10\^10 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2). No participants were enrolled at this dose level.	6 x 10^10 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 6 x 10\^10 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2). No participants were enrolled at this dose level.
Overall Study STARTED	36	0	0	0	0	0
Overall Study COMPLETED	0	0	0	0	0	0
Overall Study NOT COMPLETED	36	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	1 x 10^8 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 1 x 10\^8 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2).	5 x 10^8 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 5 x 10\^8 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2). No participants were enrolled at this dose level.	1 x 10^9 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 1 x 10\^9 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2). No participants were enrolled at this dose level.	5 x 10^9 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 5 x 10\^9 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2). No participants were enrolled at this dose level.	1 x 10^10 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 1 x 10\^10 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2). No participants were enrolled at this dose level.	6 x 10^10 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 6 x 10\^10 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2). No participants were enrolled at this dose level.
Overall Study Consented/enrolled on screening only. No participants signed the treatment consent for this study	36	0	0	0	0	0

Baseline Characteristics

T Cell Receptor Gene Therapy Targeting KK-LC-1 for Gastric, Breast, Cervical, Lung and Other KK-LC-1 Positive Epithelial Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1 x 10^8 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T Cell Receptor (TCR) T Cells n=36 Participants Non-myeloablative, lymphocyte depleting preparative regimen, followed by Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptors (TCRs) T cells plus aldesleukin at escalating doses IL-2 (Aldesleukin): Dose of 720,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period beginning within 24 hours of cell infusion and continuing for up to four days (maximum 12 doses). Cyclophosphamide: 30 mg/kg intravenous (IV) infusion over 1 hour (+ 10 min) Once daily x 2 doses (Days -6 and -5) KK-LC-1 TCR: 1 x 10\^8 transduced Kita-Kyushu Lung Cancer Antigen-1 T-Cell Receptor (KK-LC-1) (TCR) T cells. Fludarabine: 25 mg/m\^2 intravenous (IV) infusion over 30 minutes (+ 10 min) to be administered following completion of cyclophosphamide. Once daily x 5 doses (Days -6, -5, -4, -3, -2).
Age, Categorical <=18 years	0 Participants n=121 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=121 Participants
Age, Categorical >=65 years	2 Participants n=121 Participants
Age, Continuous	47.81 years STANDARD_DEVIATION 10.07 • n=121 Participants
Sex: Female, Male Female	30 Participants n=121 Participants
Sex: Female, Male Male	6 Participants n=121 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=121 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=121 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=121 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=121 Participants
Race (NIH/OMB) Asian	3 Participants n=121 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=121 Participants
Race (NIH/OMB) Black or African American	10 Participants n=121 Participants
Race (NIH/OMB) White	18 Participants n=121 Participants
Race (NIH/OMB) More than one race	0 Participants n=121 Participants
Race (NIH/OMB) Unknown or Not Reported	5 Participants n=121 Participants
Region of Enrollment United States	36 participants n=121 Participants

PRIMARY outcome

Timeframe: 3 months

Population: No participants were treated, so MTD was not determined.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: At the time of cell infusion, up to 30 days after cell infusion

Population: No participants were treated.

A DLT is all grade 3 and greater toxicities related to cell infusion, with the exception of: Cytokine Release Syndrome (CRS) that resolves \< grade 2 within 14 days of the last dose of aldesleukin; Autoimmune toxicity that resolves \< grade 2 within 14 days from starting symptoms treatment (e.g. steroids); Cardiac, gastrointestinal, dermatological, hepatic, pulmonary, renal, hematologic, neurologic toxicity, or toxicity specified in the protocol attributable to aldesleukin that resolves to grade 2 within 14 days of the last dose of aldesleukin; and Transient grade 3 hypoxia associated with cell infusion that corrects to \< grade 2 with supplemental oxygen and/or that resolves to \< grade 2 within 24 hours; and Hemorrhage due to underlying cancer or prior radiotherapy. Toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Adverse events (AEs) will be documented from the start date of chemotherapy through 40 days after the cell administration. Beyond 40days after the cells were administered, only AEs which are serious & related to the study intervention need to be recorded.

Population: The definition of an adverse event (AE) is "any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product…". Since participants on screening aren't administered a drug, then the definition of AE does not apply to them (per the protocol).

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 one of the previous outcomes mentioned.

Outcome measures

Outcome data not reported

Adverse Events

1 x 10^8 Transduced Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) T cell receptor (TCR) T cells

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Scott Norberg

National Cancer Institute

Phone: 301-275-9668

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place