Trial Outcomes & Findings for HERV-E TCR Transduced Autologous T Cells in People With Metastatic Clear Cell Renal Cell Carcinoma (NCT NCT03354390)

Last Updated: 2024-12-03

Results Overview

Toxicity profile at least possible attributed to treatment regime for each dose level using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 except for hematological toxicities Toxicity profile as measured by using the Common Terminology Criteria for Adverse Events (CTCAE version 5.0) for grade 2 and above. According to https://ctep.cancer.gov/, CTCAE is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. CTCAE grades are defined as: Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1

Target enrollment

17 participants

Primary outcome timeframe

21 days

Results posted on

2024-12-03

Participant Flow

Participant milestones

Participant milestones
Measure	Level 1: 1 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 2: 5 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 3: 1 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 4: 5 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.
Level 1 STARTED	3	0	0	0
Level 1 Treatment Completed	3	0	0	0
Level 1 COMPLETED	0	0	0	0
Level 1 NOT COMPLETED	3	0	0	0
Level 2 STARTED	0	4	0	0
Level 2 Treatment Completed	0	4	0	0
Level 2 COMPLETED	0	0	0	0
Level 2 NOT COMPLETED	0	4	0	0
Level 3 STARTED	0	0	3	0
Level 3 Treatment Completed	0	0	3	0
Level 3 COMPLETED	0	0	0	0
Level 3 NOT COMPLETED	0	0	3	0
Level 4 STARTED	0	0	0	7
Level 4 Completed Treatment	0	0	0	7
Level 4 COMPLETED	0	0	0	4
Level 4 NOT COMPLETED	0	0	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Level 1: 1 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 2: 5 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 3: 1 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 4: 5 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.
Level 1 Death	2	0	0	0
Level 1 Physician Decision	1	0	0	0
Level 2 Physician Decision	0	2	0	0
Level 2 Lack of Efficacy	0	1	0	0
Level 2 Lost to Follow-up	0	1	0	0
Level 3 Death	0	0	1	0
Level 3 Physician Decision	0	0	2	0
Level 4 Death	0	0	0	3

Baseline Characteristics

HERV-E TCR Transduced Autologous T Cells in People With Metastatic Clear Cell Renal Cell Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Level 1: 1 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 2: 5 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=4 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 3: 1 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 4: 5 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=7 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Total n=17 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	16 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	13 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	14 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	16 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	3 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	7 participants n=4 Participants	17 participants n=21 Participants

PRIMARY outcome

Timeframe: 21 days

Population: Analysis includes all participants that received HERV-E TCR transfused T-cells. Two participants did not receive the HERV-E TCR transfused T-cells because of fast clinical deterioration prior to treatment.

Outcome measures

Outcome measures
Measure	Level 1: 1 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 2: 5 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 3: 1 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 4: 5 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=6 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.
Number of Adverse Events at Least Possible Attributed to Treatment Regime for Each Dose Level Using the Common Terminology Criteria for Adverse Events Version 5.0 Except for Hematological Toxicities Grade 2 (maculopapular rash)	1 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events at Least Possible Attributed to Treatment Regime for Each Dose Level Using the Common Terminology Criteria for Adverse Events Version 5.0 Except for Hematological Toxicities Grade 3	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events at Least Possible Attributed to Treatment Regime for Each Dose Level Using the Common Terminology Criteria for Adverse Events Version 5.0 Except for Hematological Toxicities Grade 4	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events
Number of Adverse Events at Least Possible Attributed to Treatment Regime for Each Dose Level Using the Common Terminology Criteria for Adverse Events Version 5.0 Except for Hematological Toxicities Grade 5	0 Adverse events	0 Adverse events	0 Adverse events	0 Adverse events

SECONDARY outcome

Timeframe: Baseline until date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to Day 127

The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The participant's best response assignment will depend on the achievement of both measurement and confirmation criteria. Partial Response (PR): \> 30% decrease in SUL peak; minimum 0.8 unit decrease. Verification with follow-up study if anatomic criteria indicate disease progression. Progressive Disease (PD): \> 30% increase in SUL peak (minimum 0.8 unit increase in SUL peak), \> 75% increase in TLG of the 5 most active lesions, Visible increase in extent of FDG uptake, or new lesions. Verification with follow-up study if anatomic criteria indicate complete or partial response. Stable Disease (SD): Does not meet other criteria.

Outcome measures

Outcome measures
Measure	Level 1: 1 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 2: 5 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 3: 1 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 4: 5 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=6 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.
Overall Response Rate Based on the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline (Version 1.1) Stable Disease	2 Participants	0 Participants	0 Participants	2 Participants
Overall Response Rate Based on the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline (Version 1.1) Progressive Disease	1 Participants	3 Participants	3 Participants	3 Participants
Overall Response Rate Based on the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline (Version 1.1) Partial Response	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline until date of first documented response assessed up to Day 127

Population: Analysis includes all participants that received HERV-E TCR transfused T-cells and had either complete response or partial response. Two participants did not receive the HERV-E TCR transfused T-cells because of fast clinical deterioration prior to treatment.

Overall duration of response (days) based on the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) The duration of overall response is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Outcome measures

Outcome measures
Measure	Level 1: 1 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 2: 5 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 3: 1 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 4: 5 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=1 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.
Overall Duration of Response (Days) Based on the Revised Response Evaluation Criteria in Solid Tumors (RECIST) Guideline (Version 1.1)	—	—	—	127 Days

SECONDARY outcome

Timeframe: Baseline up to Day 192

Median in weeks of Progression-free survival. Progression-free survival is defined as from the time of initiation of treatment to the occurrence of disease progression or death, whichever occurs first. Disease progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (RECIST 1.1), at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Outcome measures

Outcome measures
Measure	Level 1: 1 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 2: 5 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 3: 1 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 4: 5 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=6 Participants Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.
Median In Weeks to Progression-free Survival	12.9 weeks Interval 8.0 to 15.5	4.4 weeks Interval 4.3 to 8.6	4.0 weeks Interval 3.8 to 6.6	10.9 weeks Interval 4.6 to 16.2

SECONDARY outcome

Timeframe: ongoing

Median Overall Survival. Overall survival is defined as the

Outcome measures

Outcome data not reported

Adverse Events

Level 1: 1 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Level 2: 5 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Level 3: 1 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

Level 4: 5 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight

Serious events: 2 serious events

Other events: 6 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Level 1: 1 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 participants at risk Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 2: 5 x 10^6 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=4 participants at risk Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^6 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 3: 1 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=3 participants at risk Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 1 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.	Level 4: 5 x 10^7 HERV-E TCR Transduced CD8+/CD34+ Enriched T-cells Per kg Body Weight n=7 participants at risk Participants with Metastatic Clear Cell Renal Cell Carcinoma will receive a lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by an infusion of 5 x 10\^7 HERV-E TCR transduced CD8+/CD34+ enriched T-cells per kg body weight. Following infusion of HERV-E T-cells, participants will receive IL-2 (aldesleukin) which will be administered intravenously twice a day for 14 doses.
Cardiac disorders Volume overload	33.3% 1/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
Gastrointestinal disorders Duodenal obstruction	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	25.0% 1/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
Gastrointestinal disorders Pancreatitis	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	25.0% 1/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
General disorders Back pain	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	25.0% 1/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
General disorders Disease progression	33.3% 1/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	14.3% 1/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
Hepatobiliary disorders Cholecystitis	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	14.3% 1/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
Investigations Hyperkalemia	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	25.0% 1/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
Investigations Hyponatremia	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	14.3% 1/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	25.0% 1/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	14.3% 1/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
Respiratory, thoracic and mediastinal disorders Hypoxia	33.3% 1/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	14.3% 1/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/4 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	0.00% 0/3 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.	14.3% 1/7 • Up to 5.7 years Adverse events of any grade will be collected during the first year after cell infusion or until a subject is determined to have disease progression, at which time, the subject will remain on study only for gene therapy related long-term follow up. After one year, or after a subject is determined to have disease progression, no adverse events will be collected, unless they are thought to be at least possibly related to cell infusion.

Other adverse events

Additional Information

Richard Childs, M.D. Principal Investigator

National Heart Lung and Blood Institute (NHLBI)

Phone: 301-451-7128

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place