Renal Cell Carcinoma, Metastatic
Conditions
Brief summary
The purpose of this study is to compare tumor response, progression free survival (PFS) and overall survival (OS) in newly diagnosed mRCC patients treated with Intuvax (INN: ilixadencel) pre-nephrectomy followed by Sunitinib post-nephrectomy vs Sunitinib post-nephrectomy patients.
Detailed description
Patients, all planned for nephrectomy, will be stratified according to the Heng risk criteria (high risk patients vs. intermediate risk patients) and randomized in a 2:1 ratio to receive Intuvax (INN: ilixadencel)+ Sunitinib or Sunitinib alone. Two doses of Intuvax (INN: ilixadencel) will be administered in to the primary tumour before nephrectomy. The control group will be scheduled for nephrectomy directly. All patients will start Sunitinib treatment 5-8 weeks after operation. Results from the phase I study, together with the results reported in the literature on the use of autologous dendritic cells (DCs) in combination with Sunitinib encourage Immunicum aktiebolag (AB) to further investigate the possibility of exploiting Intuvax (INN: ilixadencel) 10 million cells/dose when combined with Sunitinib for the treatment of mRCC patients.
Interventions
BIOLOGICALIntuvax (INN: ilixadencel)
Therapeutic dose (10 million cells/dose): allogeneic, pro-inflammatory dendritic cells.
DRUGSunitinib
Cytostatic/cytotoxic drug: protein kinase inhibitor .
Sponsors
TFS Trial Form Support
Accelovance
Mendus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Newly (\<6 months) diagnosed RCC (histological/cytological verification is optional) with at least one (1) CT-verified metastasis ≥10mm for which complete metastasectomy is not planned. US patients must have verified clear-cell tumor histology 2. Planned resection of primary tumor 3. Primary tumor diameter ≥40 mm 4. Candidate for first-line therapy with sunitinib initiated 5-8 weeks after nephrectomy 5. Female or male ≥18 years of age 6. Willing and able to provide informed consent 7. Adequate hematological parameters, i.e: * B-Leukocyte count ≥4.5 x10e9/L * B-Platelet count ≥150 x10e9/L * B-Hemoglobin ≥90 g/L 8. S-creatinine and S-bilirubin ≤ 1.5 x upper limit of normal (ULN). Serum alanine aminotransferase (S-ALAT) and serum aspartate aminotransferase (S-ASAT) ≤ 2.5 x ULN (or ≤5 in case of liver metastases) 9. Female who has been post-menopausal for more than one (1) year or female of childbearing potential agreeing to use a highly efficient method of contraception (i.e. a method with less than 1% failure rate \[e.g. sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner or combined birth control pills\]) Female of childbearing potential must have a negative from Screening until 90 days after last dose of Intuvax and/or until completed sunitinib treatment whichever occurs later.blood pregnancy test at Screening, and if randomized to vaccination a negative blood or urine pregnancy test within one (1) day before each dose of Intuvax) and must not be lactating. or Male agreeing to use condoms from Screening until 90 days after last dose of Intuvax and/or until completed sunitinib treatment whichever occurs later, or male having a female partner who is using a highly efficient method of contraception as described above.
Exclusion criteria
1. Life expectancy less than 4 months 2. Central nervous system (CNS) metastasis that is symptomatic or progressing or untreated or that required current therapy (e.g. evidence of new or enlarging CNS metastasis or new neurological symptoms attributable to CNS metastases) 3. Active autoimmune disease which requires treatment with systemic immunosuppressive agents, e.g. inflammatory bowel disease, multiple sclerosis, sarcoidosis, psoriasis, autoimmune hemolytic anemia, rheumatoid arthritis, systemic lupus erythematosus (SLE), vasculitis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, and other rheumatological diseases 4. Treatment with per oral systemic corticosteroids exceeding 10mg/day within seven (7) days before Screening until nephrectomy (inhaled, intranasal and local steroids accepted irrespective of dose) 5. Known cardiomyopathy and/or clinical significant abnormal ECG findings at Screening disqualifying the patient from nephrectomy and from subsequent sunitinib treatment 6. Karnofsky performance status \<70% 7. National Cancer Institute (NCI) Common Terminology criteria for Adverse Events (CTCAE) Grade 3 hemorrhage within 28 days before Screening 8. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication 9. Clinically significant gastrointestinal abnormalities 10. Uncontrolled hypertension, or uncontrolled diabetes mellitus 11. Pulmonary embolism within 12 months before screening 12. Prior history of invasive cancer within 5 years before screening, except for adequately treated in situ carcinomas or non-melanoma skin cancer 13. Ongoing infection that requires parenteral treatment with antibiotics 14. Active or latent virus disease (HIV, hepatitis B and hepatitis C) 15. Eastern Cooperative Oncology Group (ECOG) performance status \>2 after optimization of analgesics 16. Abnormal and clinical significant coagulation parameters at the discretion of the Investigator, i.e.: * Prothrombin Time - International Normalized Ratio (PT-INR) * Activated Partial Thromboplastin Time (APTT) patients being treated with anticoagulants are excluded if the coagulation parameters are outside the therapeutic intervals as described in the summary of product characteristics (SmPC) / United States prescribing information (USPI) for the administered treatment 17. Known major adverse reaction/event in connection with previously made vaccination (e.g. asthma, anaphylaxis or other serious reaction) 18. Known hypersensitivity or allergy sunitinib or to chemically related products or likely to be exacerbated to by any component of the study products 19. Prior systemic antitumour therapy within 28 days before Screening Visit. However, local radiation therapy to any area except for the abdominal/retroperitoneal area including the kidney tumour is allowed 20. Exposure to other investigational products within 28 days prior to Screening Visit 21. patients on anticoagulants for whom temporarily stop and start, supported by low molecular weight heparin (or other anticoagulation therapy at the discretion of the investigator and or per local standard of care) during vaccination and nephrectomy, is not an option 22. History of alcohol or substance abuse 23. Any reason that, in the opinion of the Investigator, contraindicates that the patient participates in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) - Days (FAS) | From the randomization to the date of death, up to 5 years after the last participant's 18-month survival data. | OS is the time from randomization until date of death. The patients who were alive at the end of study were followed for survival status (alive/date of death) through medical records, databases and public records according to the time frame below. Due to censored data, estimates of upper 95% CI could not be determined in all reporting groups. |
| Overall Survival - Days (PPS) | From the randomization to the date of death, up to 5 years after the last patient's 18-month survival data. | OS is the time from randomization until date of death. The patients who were alive at the end of study were followed for survival status (alive/date of death) through medical records, databases and public records according to the time frame below. Due to censored data, upper 95% CI could not be determined in all reporting groups. |
| 18-Months' Overall Survival Percentage (FAS) | At 18 months (544 days) | The 18-month survival percentage was defined as the percentage of patients alive 18 months after randomization. |
| 18-Months' Overall Survival Percentage (PPS) | At 18 months (544 days) | The 18-month survival percentage was defined as the percentage of patients alive 18 months after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | From first date of CR or PR until date of PD or death, up to 18 months. | The duration of response was calculated for only those patients who responded. It was the time from first objective response to first observed progression of disease or death if the death was due to disease progression (whichever came first). |
| Duration of Clinical Benefit | From first date of clinical benefit (CR, PR or SD) until date of PD or death, up to 18 months. | Disease control rate (DCR) also called Clinical Benefit Rate, was defined as the proportion of patients with CR or PR or SD. |
| Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1. | From Sunitinib-Start to progressive disease or death, up to 18 months. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by radiographic assessment: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Due to the large amount of censored data, estimates of median and/or a 95% CI could not be reliably determined in all reporting groups. Baseline data are reported for the safety data set (all patients randomized) whereas PFS is analyzed for the full analysis set (FAS). Two patients in the safety data set were not included in the FAS since they withdrew prior to start of treatment. |
| Time to Progression (TTP) | Time from Sunitinib-Start to date of either PD according to RECIST 1.1 or clinical progression as evaluated by the Investigator, up to 18 months. | Due to the large amount of censored data, estimate of upper 95% CI could not be reliably determined in all reporting groups. |
| Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells | At resection of primary tumor. | Relative number of tumor-infiltrating CD8+ T-cells in the resected primary tumor compared to number of infiltrating CD8+ T-cells in available diagnostic pre-biopsy (sample from either primary tumor or metastasis), was not to be evaluated as described in the protocol due to missing pre-biopsy samples). Instead an automated and validated quantification of percentage of CD8+ tissue in delineated tumor area was made. |
| Duration of Stable Disease | From first date of SD until PD or date of death, up to 18 months. | The duration of SD was calculated for only those patients who exhibited a best response of SD response as per RECIST v1.1. It was the time from first SD response to first observed progression of disease or death if the death was due to disease progression (whichever came first), up to 18 months. |
| Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup. | From start of sunitinib treatment up to 18 months | Objective response rate was defined as the percentage of patients with complete response (CR) and partial response (PR).Tumor response was evaluated centrally according to the RECIST 1.1 guideline. |
| Number of Participants With Specific Best Overall Response | From start of sunitinib treatment up to 18 months | The best overall response is the best response recorded from the start of the treatment sunitinib until disease progression/recurrence; taking as reference for progressive disease (PD) the smallest measurements recorded since the treatment started. In general, the patient's best response assignment depended on the achievement of the measurement criteria. |
| Disease Control Rate | From start of sunitinib treatment up to 18 months | Best overall response (CR, PR or SD) evaluated from Sunitinib-Start for patients with available data. |
Countries
Czechia, France, Hungary, Latvia, Poland, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The first patient's first visit was 28 April 2015 and last patient's last visit was 17 June 2019. Patients were recruited from Sweden (n=31), France (n=4), United States (n=2), Czech Republic (n=6), Latvia (n=6), Poland (n=12), Spain (n=18), Hungary (n=5), United Kingdom (n=4).
Pre-assignment details
117 patients with newly diagnosed metastatic renal cell cancer were screened according to the inclusion and exclusion criteria. The 88 eligible patients were randomized to either of two treatments: Intuvax (INN: ilixadencel) + Sunitinib or Sunitinib-only. Patients were stratified according to Heng criteria, as either high-risk or intermediate-risk. Results are presented by risk stratum and treatment (4 groups) and by treatment overall (2 groups), i.e. the 6 groups are not mutually exclusive.
Participants by arm
| Arm | Count |
|---|---|
| Intuvax (INN: Ilixadencel)+ Nephrectomy+Sunitinib: High-risk Stratum Two Intuvax (INN: ilixadencel) doses (10 million cells/dose) 14 days apart before nephrectomy, followed by Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).
Intuvax (INN: ilixadencel): Therapeutic dose (10 million cells/dose): allogeneic, pro-inflammatory dendritic cells.
Sunitinib: Cytostatic/cytotoxic drug: protein kinase inhibitor.
High-risk stratum. | 17 |
| Nephrectomy+Sunitinib: High-risk Stratum Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).
Sunitinib: Cytostatic/cytotoxic drug: protein kinase inhibitor.
High-risk stratum. | 8 |
| Intuvax (INN: Ilixadencel)+ Nephrectomy+Sunitinib: Intermediate-risk Stratum. Two Intuvax (INN: ilixadencel) doses (10 million cells/dose) 14 days apart before nephrectomy, followed by Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).
Intuvax (INN: ilixadencel): Therapeutic dose (10 million cells/dose): allogeneic, pro-inflammatory dendritic cells.
Sunitinib: Cytostatic/cytotoxic drug: protein kinase inhibitor.
Intermediate-risk stratum. | 41 |
| Nephrectomy+Sunitinib: Intermediate-risk Stratum Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).
Sunitinib: Cytostatic/cytotoxic drug: protein kinase inhibitor.
Intermediate-risk stratum. | 22 |
| Intuvax (INN: Ilixadencel)+ Nephrectomy+Sunitinib: Total Two Intuvax (INN: ilixadencel) doses (10 million cells/dose) 14 days apart before nephrectomy, followed by Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).
Intuvax (INN: ilixadencel): Therapeutic dose (10 million cells/dose): allogeneic, pro-inflammatory dendritic cells.
Sunitinib: Cytostatic/cytotoxic drug: protein kinase inhibitor.
High-risk and intermediate-risk strata combined. | 58 |
| Nephrectomy+Sunitinib: Total Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).
Sunitinib: Cytostatic/cytotoxic drug: protein kinase inhibitor.
High-risk and intermediate-risk strata combined. | 30 |
| Total | 176 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study (2 Total/Combined Groups) | Adverse Event | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study (2 Total/Combined Groups) | Death | 0 | 0 | 0 | 0 | 7 | 5 |
| Overall Study (2 Total/Combined Groups) | Disease progression | 0 | 0 | 0 | 0 | 23 | 14 |
| Overall Study (2 Total/Combined Groups) | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study (2 Total/Combined Groups) | Other (reason not specified) | 0 | 0 | 0 | 0 | 2 | 1 |
| Overall Study (2 Total/Combined Groups) | Physician Decision | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study (2 Total/Combined Groups) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 3 | 1 |
| Overall Study (4 Arms/Strata) | Adverse Event | 0 | 1 | 1 | 0 | 0 | 0 |
| Overall Study (4 Arms/Strata) | Death | 3 | 2 | 4 | 3 | 0 | 0 |
| Overall Study (4 Arms/Strata) | Disease progression | 8 | 5 | 15 | 9 | 0 | 0 |
| Overall Study (4 Arms/Strata) | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study (4 Arms/Strata) | Other (reason not specified) | 0 | 0 | 2 | 1 | 0 | 0 |
| Overall Study (4 Arms/Strata) | Physician Decision | 2 | 0 | 0 | 0 | 0 | 0 |
| Overall Study (4 Arms/Strata) | Withdrawal by Subject | 2 | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Intuvax (INN: Ilixadencel)+ Nephrectomy+Sunitinib: Total | Nephrectomy+Sunitinib: Total | Total | Intuvax (INN: Ilixadencel)+ Nephrectomy+Sunitinib: High-risk Stratum | Nephrectomy+Sunitinib: High-risk Stratum | Intuvax (INN: Ilixadencel)+ Nephrectomy+Sunitinib: Intermediate-risk Stratum. | Nephrectomy+Sunitinib: Intermediate-risk Stratum |
|---|---|---|---|---|---|---|---|
| Age, Continuous Age (2 total/combined groups) | 61.3 years STANDARD_DEVIATION 8.7 | 64.2 years STANDARD_DEVIATION 9.8 | 62.3 years STANDARD_DEVIATION 9.1 | — | — | — | — |
| Age, Continuous Age (4 arms/strata) | — | — | 62.3 years STANDARD_DEVIATION 9.1 | 62.0 years STANDARD_DEVIATION 9.6 | 60.5 years STANDARD_DEVIATION 7.7 | 61.0 years STANDARD_DEVIATION 8.4 | 65.5 years STANDARD_DEVIATION 10.3 |
| Race (NIH/OMB) Race (2 total/combined groups) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race (2 total/combined groups) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race (2 total/combined groups) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race (2 total/combined groups) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race (2 total/combined groups) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race (2 total/combined groups) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Race (2 total/combined groups) White | 57 Participants | 28 Participants | 85 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) race (4 arms/strata) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) race (4 arms/strata) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) race (4 arms/strata) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) race (4 arms/strata) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) race (4 arms/strata) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) race (4 arms/strata) Unknown or Not Reported | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) race (4 arms/strata) White | 0 Participants | 0 Participants | 85 Participants | 16 Participants | 6 Participants | 41 Participants | 22 Participants |
| Sex: Female, Male Sex (2 total/combined groups) Female | 13 Participants | 9 Participants | 22 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Sex (2 total/combined groups) Male | 45 Participants | 21 Participants | 66 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Sex (4 arms/strata) Female | 0 Participants | 0 Participants | 22 Participants | 2 Participants | 2 Participants | 11 Participants | 7 Participants |
| Sex: Female, Male Sex (4 arms/strata) Male | 0 Participants | 0 Participants | 66 Participants | 15 Participants | 6 Participants | 30 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 24 / 58 | 17 / 30 |
| other Total, other adverse events | 54 / 58 | 27 / 30 |
| serious Total, serious adverse events | 27 / 58 | 17 / 30 |
Outcome results
Primary
18-Months' Overall Survival Percentage (FAS)
The 18-month survival percentage was defined as the percentage of patients alive 18 months after randomization.
Time frame: At 18 months (544 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | 18-Months' Overall Survival Percentage (FAS) | 30 Percentage of participants |
| Sunitinib-only, High-risk | 18-Months' Overall Survival Percentage (FAS) | 38 Percentage of participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | 18-Months' Overall Survival Percentage (FAS) | 77 Percentage of participants |
| Sunitinib-only, Intermediate-risk | 18-Months' Overall Survival Percentage (FAS) | 76 Percentage of participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | 18-Months' Overall Survival Percentage (FAS) | 63 Percentage of participants |
| Sunitinib-only, Total (Both Strata) | 18-Months' Overall Survival Percentage (FAS) | 66 Percentage of participants |
p-value: =0.812Log Rank
Primary
18-Months' Overall Survival Percentage (PPS)
The 18-month survival percentage was defined as the percentage of patients alive 18 months after randomization.
Time frame: At 18 months (544 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | 18-Months' Overall Survival Percentage (PPS) | 31 Percentage of participants |
| Sunitinib-only, High-risk | 18-Months' Overall Survival Percentage (PPS) | 38 Percentage of participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | 18-Months' Overall Survival Percentage (PPS) | 82 Percentage of participants |
| Sunitinib-only, Intermediate-risk | 18-Months' Overall Survival Percentage (PPS) | 84 Percentage of participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | 18-Months' Overall Survival Percentage (PPS) | 68 Percentage of participants |
| Sunitinib-only, Total (Both Strata) | 18-Months' Overall Survival Percentage (PPS) | 70 Percentage of participants |
p-value: =0.861Log Rank
Primary
Overall Survival - Days (PPS)
OS is the time from randomization until date of death. The patients who were alive at the end of study were followed for survival status (alive/date of death) through medical records, databases and public records according to the time frame below. Due to censored data, upper 95% CI could not be determined in all reporting groups.
Time frame: From the randomization to the date of death, up to 5 years after the last patient's 18-month survival data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Overall Survival - Days (PPS) | 352 days |
| Sunitinib-only, High-risk | Overall Survival - Days (PPS) | 282 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Overall Survival - Days (PPS) | 1745 days |
| Sunitinib-only, Intermediate-risk | Overall Survival - Days (PPS) | 1185 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Overall Survival - Days (PPS) | 1265 days |
| Sunitinib-only, Total (Both Strata) | Overall Survival - Days (PPS) | 1024 days |
p-value: 0.59695% CI: [0.268, 2.134]Log Rank
p-value: 0.28595% CI: [0.308, 1.418]Log Rank
p-value: 0.2495% CI: [0.378, 1.29]Log Rank
Primary
Overall Survival (OS) - Days (FAS)
OS is the time from randomization until date of death. The patients who were alive at the end of study were followed for survival status (alive/date of death) through medical records, databases and public records according to the time frame below. Due to censored data, estimates of upper 95% CI could not be determined in all reporting groups.
Time frame: From the randomization to the date of death, up to 5 years after the last participant's 18-month survival data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Overall Survival (OS) - Days (FAS) | 323 days |
| Sunitinib-only, High-risk | Overall Survival (OS) - Days (FAS) | 282 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Overall Survival (OS) - Days (FAS) | 1270 days |
| Sunitinib-only, Intermediate-risk | Overall Survival (OS) - Days (FAS) | 1099 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Overall Survival (OS) - Days (FAS) | 1082 days |
| Sunitinib-only, Total (Both Strata) | Overall Survival (OS) - Days (FAS) | 770 days |
p-value: 0.96495% CI: [0.371, 2.579]Log Rank
p-value: 0.16395% CI: [0.314, 1.222]Log Rank
p-value: 0.2595% CI: [0.421, 1.27]Log Rank
Secondary
Disease Control Rate
Best overall response (CR, PR or SD) evaluated from Sunitinib-Start for patients with available data.
Time frame: From start of sunitinib treatment up to 18 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Disease Control Rate | 7 Participants |
| Sunitinib-only, High-risk | Disease Control Rate | 6 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Disease Control Rate | 28 Participants |
| Sunitinib-only, Intermediate-risk | Disease Control Rate | 15 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Disease Control Rate | 35 Participants |
| Sunitinib-only, Total (Both Strata) | Disease Control Rate | 21 Participants |
Secondary
Duration of Clinical Benefit
Disease control rate (DCR) also called Clinical Benefit Rate, was defined as the proportion of patients with CR or PR or SD.
Time frame: From first date of clinical benefit (CR, PR or SD) until date of PD or death, up to 18 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Duration of Clinical Benefit | 212.0 days |
| Sunitinib-only, High-risk | Duration of Clinical Benefit | 60.0 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Duration of Clinical Benefit | 323.5 days |
| Sunitinib-only, Intermediate-risk | Duration of Clinical Benefit | 295.0 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Duration of Clinical Benefit | 219.0 days |
| Sunitinib-only, Total (Both Strata) | Duration of Clinical Benefit | 133.0 days |
| Full Analysis Set (FAS) | Duration of Clinical Benefit | 211.0 days |
Secondary
Duration of Response
The duration of response was calculated for only those patients who responded. It was the time from first objective response to first observed progression of disease or death if the death was due to disease progression (whichever came first).
Time frame: From first date of CR or PR until date of PD or death, up to 18 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Duration of Response | 175.0 days |
| Sunitinib-only, High-risk | Duration of Response | 81.5 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Duration of Response | 316.0 days |
| Sunitinib-only, Intermediate-risk | Duration of Response | 108.0 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Duration of Response | 215.0 days |
| Sunitinib-only, Total (Both Strata) | Duration of Response | 87.0 days |
| Full Analysis Set (FAS) | Duration of Response | 169.5 days |
Secondary
Duration of Stable Disease
The duration of SD was calculated for only those patients who exhibited a best response of SD response as per RECIST v1.1. It was the time from first SD response to first observed progression of disease or death if the death was due to disease progression (whichever came first), up to 18 months.
Time frame: From first date of SD until PD or date of death, up to 18 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Duration of Stable Disease | 63.5 days |
| Sunitinib-only, High-risk | Duration of Stable Disease | 10.5 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Duration of Stable Disease | 169.0 days |
| Sunitinib-only, Intermediate-risk | Duration of Stable Disease | 210.0 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Duration of Stable Disease | 126.0 days |
| Sunitinib-only, Total (Both Strata) | Duration of Stable Disease | 133.0 days |
| Full Analysis Set (FAS) | Duration of Stable Disease | 129.5 days |
Secondary
Number of Participants With Specific Best Overall Response
The best overall response is the best response recorded from the start of the treatment sunitinib until disease progression/recurrence; taking as reference for progressive disease (PD) the smallest measurements recorded since the treatment started. In general, the patient's best response assignment depended on the achievement of the measurement criteria.
Time frame: From start of sunitinib treatment up to 18 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Number of Participants With Specific Best Overall Response | Complete Response (CR) | 1 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Number of Participants With Specific Best Overall Response | Partial Response (PR) | 4 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Number of Participants With Specific Best Overall Response | Progressive Disease (PD) | 4 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Number of Participants With Specific Best Overall Response | Stable Disease (SD) | 2 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Number of Participants With Specific Best Overall Response | Non-CR/Non-PD | 2 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Number of Participants With Specific Best Overall Response | No Disease (ND) | 0 Participants |
| Sunitinib-only, High-risk | Number of Participants With Specific Best Overall Response | Partial Response (PR) | 4 Participants |
| Sunitinib-only, High-risk | Number of Participants With Specific Best Overall Response | Stable Disease (SD) | 2 Participants |
| Sunitinib-only, High-risk | Number of Participants With Specific Best Overall Response | No Disease (ND) | 0 Participants |
| Sunitinib-only, High-risk | Number of Participants With Specific Best Overall Response | Complete Response (CR) | 0 Participants |
| Sunitinib-only, High-risk | Number of Participants With Specific Best Overall Response | Progressive Disease (PD) | 0 Participants |
| Sunitinib-only, High-risk | Number of Participants With Specific Best Overall Response | Non-CR/Non-PD | 0 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Number of Participants With Specific Best Overall Response | No Disease (ND) | 1 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Number of Participants With Specific Best Overall Response | Non-CR/Non-PD | 0 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Number of Participants With Specific Best Overall Response | Stable Disease (SD) | 13 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Number of Participants With Specific Best Overall Response | Progressive Disease (PD) | 3 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Number of Participants With Specific Best Overall Response | Complete Response (CR) | 4 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Number of Participants With Specific Best Overall Response | Partial Response (PR) | 11 Participants |
| Sunitinib-only, Intermediate-risk | Number of Participants With Specific Best Overall Response | Stable Disease (SD) | 7 Participants |
| Sunitinib-only, Intermediate-risk | Number of Participants With Specific Best Overall Response | Partial Response (PR) | 7 Participants |
| Sunitinib-only, Intermediate-risk | Number of Participants With Specific Best Overall Response | Progressive Disease (PD) | 2 Participants |
| Sunitinib-only, Intermediate-risk | Number of Participants With Specific Best Overall Response | No Disease (ND) | 1 Participants |
| Sunitinib-only, Intermediate-risk | Number of Participants With Specific Best Overall Response | Non-CR/Non-PD | 1 Participants |
| Sunitinib-only, Intermediate-risk | Number of Participants With Specific Best Overall Response | Complete Response (CR) | 1 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Number of Participants With Specific Best Overall Response | Complete Response (CR) | 5 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Number of Participants With Specific Best Overall Response | Non-CR/Non-PD | 2 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Number of Participants With Specific Best Overall Response | Partial Response (PR) | 15 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Number of Participants With Specific Best Overall Response | Progressive Disease (PD) | 7 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Number of Participants With Specific Best Overall Response | Stable Disease (SD) | 15 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Number of Participants With Specific Best Overall Response | No Disease (ND) | 1 Participants |
| Sunitinib-only, Total (Both Strata) | Number of Participants With Specific Best Overall Response | Stable Disease (SD) | 9 Participants |
| Sunitinib-only, Total (Both Strata) | Number of Participants With Specific Best Overall Response | Progressive Disease (PD) | 2 Participants |
| Sunitinib-only, Total (Both Strata) | Number of Participants With Specific Best Overall Response | Non-CR/Non-PD | 1 Participants |
| Sunitinib-only, Total (Both Strata) | Number of Participants With Specific Best Overall Response | No Disease (ND) | 1 Participants |
| Sunitinib-only, Total (Both Strata) | Number of Participants With Specific Best Overall Response | Partial Response (PR) | 11 Participants |
| Sunitinib-only, Total (Both Strata) | Number of Participants With Specific Best Overall Response | Complete Response (CR) | 1 Participants |
Secondary
Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup.
Objective response rate was defined as the percentage of patients with complete response (CR) and partial response (PR).Tumor response was evaluated centrally according to the RECIST 1.1 guideline.
Time frame: From start of sunitinib treatment up to 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup. | 38.5 Percentage of participants |
| Sunitinib-only, High-risk | Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup. | 66.7 Percentage of participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup. | 46.9 Percentage of participants |
| Sunitinib-only, Intermediate-risk | Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup. | 42.1 Percentage of participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup. | 44.4 Percentage of participants |
| Sunitinib-only, Total (Both Strata) | Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup. | 48.0 Percentage of participants |
Secondary
Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells
Relative number of tumor-infiltrating CD8+ T-cells in the resected primary tumor compared to number of infiltrating CD8+ T-cells in available diagnostic pre-biopsy (sample from either primary tumor or metastasis), was not to be evaluated as described in the protocol due to missing pre-biopsy samples). Instead an automated and validated quantification of percentage of CD8+ tissue in delineated tumor area was made.
Time frame: At resection of primary tumor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells | 1.0 Percentage of tumor area |
| Sunitinib-only, High-risk | Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells | 1.1 Percentage of tumor area |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells | 1.2 Percentage of tumor area |
| Sunitinib-only, Intermediate-risk | Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells | 0.8 Percentage of tumor area |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells | 1.1 Percentage of tumor area |
| Sunitinib-only, Total (Both Strata) | Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells | 0.8 Percentage of tumor area |
| Full Analysis Set (FAS) | Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells | 1.1 Percentage of tumor area |
Secondary
Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by radiographic assessment: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Due to the large amount of censored data, estimates of median and/or a 95% CI could not be reliably determined in all reporting groups. Baseline data are reported for the safety data set (all patients randomized) whereas PFS is analyzed for the full analysis set (FAS). Two patients in the safety data set were not included in the FAS since they withdrew prior to start of treatment.
Time frame: From Sunitinib-Start to progressive disease or death, up to 18 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1. | 254 days |
| Sunitinib-only, High-risk | Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1. | NA days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1. | 478 days |
| Sunitinib-only, Intermediate-risk | Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1. | 417 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1. | 360 days |
| Sunitinib-only, Total (Both Strata) | Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1. | 337 days |
Secondary
Time to Progression (TTP)
Due to the large amount of censored data, estimate of upper 95% CI could not be reliably determined in all reporting groups.
Time frame: Time from Sunitinib-Start to date of either PD according to RECIST 1.1 or clinical progression as evaluated by the Investigator, up to 18 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Time to Progression (TTP) | 169 days |
| Sunitinib-only, High-risk | Time to Progression (TTP) | 143 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Time to Progression (TTP) | 388 days |
| Sunitinib-only, Intermediate-risk | Time to Progression (TTP) | 417 days |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Time to Progression (TTP) | 254 days |
| Sunitinib-only, Total (Both Strata) | Time to Progression (TTP) | 251 days |
Post Hoc
Confirmed Best Overall Response
Number of patients with the individual's best overall response at initial CT/MRI confirmed by a best response level at least 4 weeks later in accordance with RECIST 1.1.
Time frame: From start of sunitinib treatment up to 18 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Confirmed Best Overall Response | Complete response (CR) | 0 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Confirmed Best Overall Response | Missing | 7 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Confirmed Best Overall Response | Stable disease (SD) | 1 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Confirmed Best Overall Response | Partial response (PR) | 5 Participants |
| Sunitinib-only, High-risk | Confirmed Best Overall Response | Missing | 3 Participants |
| Sunitinib-only, High-risk | Confirmed Best Overall Response | Partial response (PR) | 2 Participants |
| Sunitinib-only, High-risk | Confirmed Best Overall Response | Complete response (CR) | 0 Participants |
| Sunitinib-only, High-risk | Confirmed Best Overall Response | Stable disease (SD) | 1 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Confirmed Best Overall Response | Complete response (CR) | 3 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Confirmed Best Overall Response | Missing | 8 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Confirmed Best Overall Response | Partial response (PR) | 11 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Confirmed Best Overall Response | Stable disease (SD) | 10 Participants |
| Sunitinib-only, Intermediate-risk | Confirmed Best Overall Response | Missing | 6 Participants |
| Sunitinib-only, Intermediate-risk | Confirmed Best Overall Response | Partial response (PR) | 4 Participants |
| Sunitinib-only, Intermediate-risk | Confirmed Best Overall Response | Stable disease (SD) | 9 Participants |
| Sunitinib-only, Intermediate-risk | Confirmed Best Overall Response | Complete response (CR) | 0 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Confirmed Best Overall Response | Stable disease (SD) | 11 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Confirmed Best Overall Response | Complete response (CR) | 3 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Confirmed Best Overall Response | Missing | 15 Participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Confirmed Best Overall Response | Partial response (PR) | 16 Participants |
| Sunitinib-only, Total (Both Strata) | Confirmed Best Overall Response | Missing | 9 Participants |
| Sunitinib-only, Total (Both Strata) | Confirmed Best Overall Response | Complete response (CR) | 0 Participants |
| Sunitinib-only, Total (Both Strata) | Confirmed Best Overall Response | Partial response (PR) | 6 Participants |
| Sunitinib-only, Total (Both Strata) | Confirmed Best Overall Response | Stable disease (SD) | 10 Participants |
Post Hoc
Confirmed Objective Response Rate
Percentage of patients with the individual's confirmed best overall response scored as CR or PR at least 4 weeks apart from the CT/MRI with the initial best response of CR or PR. Tumor response was evaluated centrally according to the response evaluation criteria in solid tumors (RECIST) 1.1 guideline.
Time frame: From start of sunitinib treatment up to 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Confirmed Objective Response Rate | 38.5 Percentage of participants |
| Sunitinib-only, High-risk | Confirmed Objective Response Rate | 33.3 Percentage of participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Confirmed Objective Response Rate | 43.8 Percentage of participants |
| Sunitinib-only, Intermediate-risk | Confirmed Objective Response Rate | 21.1 Percentage of participants |
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Confirmed Objective Response Rate | 42.2 Percentage of participants |
| Sunitinib-only, Total (Both Strata) | Confirmed Objective Response Rate | 24.0 Percentage of participants |