MERECA: Intratumoral Vaccination With Intuvax Pre-nephrectomy Followed by Sunitinib Post-nephrectomy vs Sunitinib Post-nephrectomy in Newly Diagnosed Metastatic Renal Cell Carcinoma (mRCC)
Sponsor
Immunicum AB (Industry)
Overall Status
Completed
CT.gov ID
NCT02432846
Collaborator
TFS Trial Form Support (Industry), Accelovance (Industry)
88
28
2
70
3.1
0
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
88 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Randomized, Controlled, Multicenter, Phase II Study Evaluating Safety and Efficacy of Intratumorally Administered Intuvax Pre-nephrectomy Followed by Sunitinib Post-nephrectomy, Compared to Sunitinib Post-nephrectomy in Metastatic Renal Cell Carcinoma Patients
Study Start Date
:
Apr 1, 2015
Actual Primary Completion Date
:
Jan 31, 2021
Actual Study Completion Date
:
Jan 31, 2021
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Intuvax (INN: ilixadencel)+ Nephrectomy+Sunitinib 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). |
Biological: Intuvax (INN: ilixadencel)
Therapeutic dose (10 million cells/dose): allogeneic, pro-inflammatory dendritic cells.
Other Names:
Drug: Sunitinib
Cytostatic/cytotoxic drug: protein kinase inhibitor .
Other Names:
|
| Active Comparator: Nephrectomy+Sunitinib Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening). |
Drug: Sunitinib
Cytostatic/cytotoxic drug: protein kinase inhibitor .
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
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
-
Planned resection of primary tumor
-
Primary tumor diameter ≥40 mm
-
Candidate for first-line therapy with sunitinib initiated 5-8 weeks after nephrectomy
-
Female or male ≥18 years of age
-
Willing and able to provide informed consent
-
Adequate hematological parameters, i.e:
-
B-Leukocyte count ≥4.5 x10e9/L
-
B-Platelet count ≥150 x10e9/L
-
B-Hemoglobin ≥90 g/L
-
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)
-
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:
-
Life expectancy less than 4 months
-
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)
-
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
-
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)
-
Known cardiomyopathy and/or clinical significant abnormal ECG findings at Screening disqualifying the patient from nephrectomy and from subsequent sunitinib treatment
-
Karnofsky performance status <70%
-
National Cancer Institute (NCI) Common Terminology criteria for Adverse Events (CTCAE) Grade 3 hemorrhage within 28 days before Screening
-
Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
-
Clinically significant gastrointestinal abnormalities
-
Uncontrolled hypertension, or uncontrolled diabetes mellitus
-
Pulmonary embolism within 12 months before screening
-
Prior history of invasive cancer within 5 years before screening, except for adequately treated in situ carcinomas or non-melanoma skin cancer
-
Ongoing infection that requires parenteral treatment with antibiotics
-
Active or latent virus disease (HIV, hepatitis B and hepatitis C)
-
Eastern Cooperative Oncology Group (ECOG) performance status >2 after optimization of analgesics
-
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
-
Known major adverse reaction/event in connection with previously made vaccination (e.g. asthma, anaphylaxis or other serious reaction)
-
Known hypersensitivity or allergy sunitinib or to chemically related products or likely to be exacerbated to by any component of the study products
-
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
-
Exposure to other investigational products within 28 days prior to Screening Visit
-
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
-
History of alcohol or substance abuse
-
Any reason that, in the opinion of the Investigator, contraindicates that the patient participates in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Illinois | Chicago | Illinois | United States | 60605 |
| 2 | Rush University | Chicago | Illinois | United States | 60612 |
| 3 | University of Iowa | Iowa City | Iowa | United States | 52242 |
| 4 | Health Partners Institute | Saint Paul | Minnesota | United States | 55101 |
| 5 | Duke Cancer Institute | Durham | North Carolina | United States | 27710 |
| 6 | University Hospital Olomouc | Olomouc | Czechia | 779 00 | |
| 7 | Centre Hospitalier Universitaire d'Angers | Angers Cedex 9 | France | 49933 | |
| 8 | Centre Hospitalier Universitaire de Toulouse-Hôpital Rangueil | Toulouse | France | 31059 | |
| 9 | University of Debrecen | Debrecen | Hungary | 4032 | |
| 10 | Szent-Györgyi Albert Klinikai Központ | Szeged | Hungary | 6725 | |
| 11 | Pauls Stradins Clinical University Hospital | Riga | Latvia | LV-1002 | |
| 12 | Riga East Clinical University Hospital | Riga | Latvia | LV-1079 | |
| 13 | Niepubliczny Zakład Opieki Zdrowotnej Vesalius Sp. z o.o. | Kraków | Poland | 31-108 | |
| 14 | Wojewodzki Szpital Specjalistyczny | Lublin | Poland | 20-718 | |
| 15 | Military Institute of Medicine | Warsaw | Poland | 04-141 | |
| 16 | Mazowiecki Szpital Onkologiczny | Wieliszew | Poland | 05-135 | |
| 17 | Hospital Universitari Germans Trias i Pujol | Badalona | Spain | 08916 | |
| 18 | Hospital Clinic de Barcelona | Barcelona | Spain | 08036 | |
| 19 | Hospital de la Santa Creu i Sant Pau | Barcelona | Spain | 08041 | |
| 20 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
| 21 | Hospital Universitario Puerta de Hierro Majadahonda | Majadahonda | Spain | 28222 | |
| 22 | Hospital Universitari Parc Tauli | Sabadell | Spain | 08208 | |
| 23 | Sahlgrenska University Hospital | Göteborg | Sweden | SE-413 45 | |
| 24 | Karolinska University Hospital | Huddinge | Sweden | SE-141 86 | |
| 25 | Umeå University Hospital | Umeå | Sweden | SE-901 85 | |
| 26 | Uppsala University Hospital | Uppsala | Sweden | SE-751 85 | |
| 27 | The Churchill Hospital | Oxford | United Kingdom | OX3 7LE | |
| 28 | Royal Preston Hospital | Preston | United Kingdom | PR2 9HT |
Sponsors and Collaborators
- Immunicum AB
- TFS Trial Form Support
- Accelovance
Investigators
- Principal Investigator: Börje Ljungberg, MD, Prof, Umeå University Hospital
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Immunicum AB
ClinicalTrials.gov Identifier:
NCT02432846
Other Study ID Numbers:
- IM-201
- 2014-004510-28
First Posted:
May 4, 2015
Last Update Posted:
Aug 22, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
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 Detail | 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. |
| Arm/Group Title | 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 | Intuvax (INN: Ilixadencel)+ Nephrectomy+Sunitinib: Total | Nephrectomy+Sunitinib: Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. |
| Period Title: Overall Study (4 Arms/Strata) | ||||||
| STARTED | 17 | 8 | 41 | 22 | 0 | 0 |
| COMPLETED | 2 | 0 | 17 | 8 | 0 | 0 |
| NOT COMPLETED | 15 | 8 | 24 | 14 | 0 | 0 |
| Period Title: Overall Study (4 Arms/Strata) | ||||||
| STARTED | 0 | 0 | 0 | 0 | 58 | 30 |
| COMPLETED | 0 | 0 | 0 | 0 | 19 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 39 | 22 |
Baseline Characteristics
| Arm/Group Title | 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 | Intuvax (INN: Ilixadencel)+ Nephrectomy+Sunitinib: Total | Nephrectomy+Sunitinib: Total | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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. | 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. | 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. | 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. | 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. | 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. | Total of all reporting groups |
| Overall Participants | 17 | 8 | 41 | 22 | 58 | 30 | 176 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Age (4 arms/strata) |
62.0
(9.6)
|
60.5
(7.7)
|
61.0
(8.4)
|
65.5
(10.3)
|
62.3
(9.1)
|
||
| Age (2 total/combined groups) |
61.3
(8.7)
|
64.2
(9.8)
|
62.3
(9.1)
|
||||
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
2
11.8%
|
2
25%
|
11
26.8%
|
7
31.8%
|
0
0%
|
0
0%
|
22
12.5%
|
| Male |
15
88.2%
|
6
75%
|
30
73.2%
|
15
68.2%
|
0
0%
|
0
0%
|
66
37.5%
|
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
13
22.4%
|
9
30%
|
22
12.5%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
45
77.6%
|
21
70%
|
66
37.5%
|
| Race (NIH/OMB) (Count of Participants) | |||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
16
94.1%
|
6
75%
|
41
100%
|
22
100%
|
0
0%
|
0
0%
|
85
48.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
5.9%
|
2
25%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
1.7%
|
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
57
98.3%
|
28
93.3%
|
85
48.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.7%
|
2
6.7%
|
3
1.7%
|
Outcome Measures
| Title | Overall Survival (OS) - Days (FAS) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined |
| Measure Participants | 16 | 8 | 40 | 22 | 56 | 30 |
| Median (95% Confidence Interval) [days] |
323
|
282
|
1270
|
1099
|
1082
|
770
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk, Sunitinib-only, High-risk |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Exploratory superiority (non-powered) | |
| Statistical Test of Hypothesis | p-Value | 0.964 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.978 | |
| Confidence Interval |
(2-Sided) 95% 0.371 to 2.579 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk, Sunitinib-only, Intermediate-risk |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Exploratory superiority (non-powered) | |
| Statistical Test of Hypothesis | p-Value | 0.163 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.619 | |
| Confidence Interval |
(2-Sided) 95% 0.314 to 1.222 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata), Sunitinib-only, Total (Both Strata) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Exploratory superiority (non-powered) | |
| Statistical Test of Hypothesis | p-Value | 0.250 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.732 | |
| Confidence Interval |
(2-Sided) 95% 0.421 to 1.270 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival - Days (PPS) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate-risk strata combined | Sunitinib-only, high and intermediate risk strata combined |
| Measure Participants | 12 | 8 | 34 | 19 | 46 | 27 |
| Median (95% Confidence Interval) [days] |
352
|
282
|
1745
|
1185
|
1265
|
1024
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk, Sunitinib-only, High-risk |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Exploratory superiority (non-powered) | |
| Statistical Test of Hypothesis | p-Value | 0.596 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.756 | |
| Confidence Interval |
(2-Sided) 95% 0.268 to 2.134 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk, Sunitinib-only, Intermediate-risk |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Exploratory superiority (non-powered) | |
| Statistical Test of Hypothesis | p-Value | 0.285 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.661 | |
| Confidence Interval |
(2-Sided) 95% 0.308 to 1.418 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata), Sunitinib-only, Total (Both Strata) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Exploratory superiority (non-powered) | |
| Statistical Test of Hypothesis | p-Value | 0.240 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.699 | |
| Confidence Interval |
(2-Sided) 95% 0.378 to 1.290 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 18-Months' Overall Survival Percentage (FAS) |
|---|---|
| Description | The 18-month survival percentage was defined as the percentage of patients alive 18 months after randomization. |
| Time Frame | At 18 months (544 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined |
| Measure Participants | 16 | 8 | 40 | 22 | 56 | 30 |
| Number [Percentage of participants] |
30
176.5%
|
38
475%
|
77
187.8%
|
76
345.5%
|
63
108.6%
|
66
220%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk, Sunitinib-only, High-risk, Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk, Sunitinib-only, Intermediate-risk |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Exploratory superiority (non-powered) | |
| Statistical Test of Hypothesis | p-Value | = 0.812 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | 18-Months' Overall Survival Percentage (PPS) |
|---|---|
| Description | The 18-month survival percentage was defined as the percentage of patients alive 18 months after randomization. |
| Time Frame | At 18 months (544 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined |
| Measure Participants | 12 | 8 | 34 | 19 | 46 | 27 |
| Number [Percentage of participants] |
31
182.4%
|
38
475%
|
82
200%
|
84
381.8%
|
68
117.2%
|
70
233.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk, Sunitinib-only, High-risk, Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk, Sunitinib-only, Intermediate-risk |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | Exploratory superiority (non-powered) | |
| Statistical Test of Hypothesis | p-Value | = 0.861 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Progression Free Survival (PFS) From Start of Sunitinib According to RECIST 1.1. |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined |
| Measure Participants | 13 | 6 | 33 | 19 | 46 | 25 |
| Median (95% Confidence Interval) [days] |
254
|
NA
|
478
|
417
|
360
|
337
|
| Title | Objective Response Rate (ORR) From Start of Sunitinib Treatment and Duration of Response in Each Subgroup. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined |
| Measure Participants | 13 | 6 | 32 | 19 | 45 | 25 |
| Number [Percentage of participants] |
38.5
226.5%
|
66.7
833.8%
|
46.9
114.4%
|
42.1
191.4%
|
44.4
76.6%
|
48.0
160%
|
| Title | Number of Participants With Specific Best Overall Response |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined |
| Measure Participants | 13 | 6 | 32 | 19 | 45 | 25 |
| Complete Response (CR) |
1
5.9%
|
0
0%
|
4
9.8%
|
1
4.5%
|
5
8.6%
|
1
3.3%
|
| Partial Response (PR) |
4
23.5%
|
4
50%
|
11
26.8%
|
7
31.8%
|
15
25.9%
|
11
36.7%
|
| Progressive Disease (PD) |
4
23.5%
|
0
0%
|
3
7.3%
|
2
9.1%
|
7
12.1%
|
2
6.7%
|
| Stable Disease (SD) |
2
11.8%
|
2
25%
|
13
31.7%
|
7
31.8%
|
15
25.9%
|
9
30%
|
| Non-CR/Non-PD |
2
11.8%
|
0
0%
|
0
0%
|
1
4.5%
|
2
3.4%
|
1
3.3%
|
| No Disease (ND) |
0
0%
|
0
0%
|
1
2.4%
|
1
4.5%
|
1
1.7%
|
1
3.3%
|
| Title | Disease Control Rate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined |
| Measure Participants | 13 | 6 | 32 | 19 | 45 | 25 |
| Count of Participants [Participants] |
7
41.2%
|
6
75%
|
28
68.3%
|
15
68.2%
|
35
60.3%
|
21
70%
|
| Title | Duration of Response |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) | Full Analysis Set (FAS) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined | All patients randomized being evaluable for any high or intermediate stratum related efficacy endpoint. |
| Measure Participants | 5 | 4 | 15 | 8 | 20 | 12 | 32 |
| Median (Full Range) [days] |
175.0
|
81.5
|
316.0
|
108.0
|
215.0
|
87.0
|
169.5
|
| Title | Duration of Clinical Benefit |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) | Full Analysis Set (FAS) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined | All patients randomized being evaluable for any high or intermediate stratum related efficacy endpoint. |
| Measure Participants | 7 | 6 | 28 | 15 | 35 | 21 | 56 |
| Median (Full Range) [days] |
212.0
|
60.0
|
323.5
|
295.0
|
219.0
|
133.0
|
211.0
|
| Title | Duration of Stable Disease |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) | Full Analysis Set (FAS) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined | All patients randomized being evaluable for any high or intermediate stratum related efficacy endpoint. |
| Measure Participants | 2 | 2 | 13 | 7 | 15 | 9 | 24 |
| Median (Full Range) [days] |
63.5
|
10.5
|
169.0
|
210.0
|
126.0
|
133.0
|
129.5
|
| Title | Time to Progression (TTP) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined |
| Measure Participants | 13 | 6 | 33 | 19 | 46 | 25 |
| Median (95% Confidence Interval) [days] |
169
|
143
|
388
|
417
|
254
|
251
|
| Title | Percentage of Tumor Area With Infiltrating Cluster of Differentiation 8+ (CD8+) T-cells |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) | Full Analysis Set (FAS) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined | All patients randomized being evaluable for any high or intermediate stratum related efficacy endpoint. |
| Measure Participants | 14 | 7 | 38 | 20 | 52 | 27 | 79 |
| Median (Full Range) [Percentage of tumor area] |
1.0
|
1.1
|
1.2
|
0.8
|
1.1
|
0.8
|
1.1
|
| Title | Confirmed Objective Response Rate |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined |
| Measure Participants | 13 | 6 | 32 | 19 | 45 | 25 |
| Number [Percentage of participants] |
38.5
226.5%
|
33.3
416.3%
|
43.8
106.8%
|
21.1
95.9%
|
42.2
72.8%
|
24.0
80%
|
| Title | Confirmed Best Overall Response |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, High-risk | Sunitinib-only, High-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Intermediate-risk | Sunitinib-only, Intermediate-risk | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high-risk stratum | Sunitinib-only, high-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, intermediate-risk stratum | Sunitinib-only, intermediate-risk stratum | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined |
| Measure Participants | 13 | 6 | 32 | 19 | 45 | 25 |
| Complete response (CR) |
0
0%
|
0
0%
|
3
7.3%
|
0
0%
|
3
5.2%
|
0
0%
|
| Partial response (PR) |
5
29.4%
|
2
25%
|
11
26.8%
|
4
18.2%
|
16
27.6%
|
6
20%
|
| Stable disease (SD) |
1
5.9%
|
1
12.5%
|
10
24.4%
|
9
40.9%
|
11
19%
|
10
33.3%
|
| Missing |
7
41.2%
|
3
37.5%
|
8
19.5%
|
6
27.3%
|
15
25.9%
|
9
30%
|
Adverse Events
| Time Frame | AEs and SAEs were collected from first dose to last follow-up, up to 18 months. All-cause mortality was collected from first dose up to 5 years after last participant's 18-month survival data. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Adverse events are presented overall by treatment, not further split by strata, since the split by strata is deemed to be relevant for efficacy endpoints only. | |||
| Arm/Group Title | Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) | ||
| Arm/Group Description | Intuvax (INN: ilixadencel) + sunitinib, high and intermediate risk strata combined | Sunitinib-only, high and intermediate risk strata combined | ||
All Cause Mortality |
||||
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 24/58 (41.4%) | 17/30 (56.7%) | ||
Serious Adverse Events |
||||
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 27/58 (46.6%) | 17/30 (56.7%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/58 (1.7%) | 2 | 0/30 (0%) | 0 |
| Pancytopenia | 1/58 (1.7%) | 1 | 1/30 (3.3%) | 1 |
| Cardiac disorders | ||||
| Left ventricular dysfunction | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Gastrointestinal disorders | ||||
| Diarrhoea | 0/58 (0%) | 0 | 2/30 (6.7%) | 2 |
| Gastrointestinal inflammation | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Intestinal perforation | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Nausea | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Pancreatitis acute | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Vomiting | 2/58 (3.4%) | 2 | 0/30 (0%) | 0 |
| General disorders | ||||
| Asthenia | 1/58 (1.7%) | 1 | 2/30 (6.7%) | 2 |
| Death | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| General physical health deterioration | 3/58 (5.2%) | 3 | 1/30 (3.3%) | 1 |
| Multi-organ disorder | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Pyrexia | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Hepatobiliary disorders | ||||
| Cholecystitis acute | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Infections and infestations | ||||
| Gastrointestinal infection | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Lymphangitis | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Pneumonia | 0/58 (0%) | 0 | 2/30 (6.7%) | 2 |
| Post procedural infection | 2/58 (3.4%) | 2 | 0/30 (0%) | 0 |
| Septic shock | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Urinary tract infection | 2/58 (3.4%) | 2 | 0/30 (0%) | 0 |
| Gastrointestinal viral infection | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Humerus fracture | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Pelvic fracture | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Post procedural haemorrhage | 2/58 (3.4%) | 2 | 0/30 (0%) | 0 |
| Procedural pain | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Wound evisceration | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Investigations | ||||
| Blood thyroid stimulating hormone increased | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| General physical condition abnormal | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 2/58 (3.4%) | 2 | 0/30 (0%) | 0 |
| Hypercalcaemia | 1/58 (1.7%) | 1 | 2/30 (6.7%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Back pain | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Bone pain | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Muscular weakness | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Pathological fracture | 0/58 (0%) | 0 | 2/30 (6.7%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Malignant pleural effusion | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Metastatic bone disease prophylaxis | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Thyroid cancer | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Nervous system disorders | ||||
| Aphasia | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Brain oedema | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Cerebrovascular accident | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Hemiparesis | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Paresis | 1/58 (1.7%) | 1 | 1/30 (3.3%) | 1 |
| Sciatica | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Spinal cord compression | 1/58 (1.7%) | 1 | 1/30 (3.3%) | 1 |
| Transient ischaemic attack | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Psychiatric disorders | ||||
| Confusional state | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Renal and urinary disorders | ||||
| Renal failure | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Uterine haemorrhage | 1/58 (1.7%) | 1 | 0/30 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Pleural effusion | 1/58 (1.7%) | 1 | 1/30 (3.3%) | 1 |
| Pulmonary embolism | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
| Pulmonary oedema | 0/58 (0%) | 0 | 1/30 (3.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Intuvax (INN: Ilixadencel) + Sunitinib, Total (Both Strata) | Sunitinib-only, Total (Both Strata) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 54/58 (93.1%) | 27/30 (90%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 14/58 (24.1%) | 19 | 4/30 (13.3%) | 4 |
| Neutropenia | 4/58 (6.9%) | 5 | 1/30 (3.3%) | 1 |
| Thrombocytopenia | 5/58 (8.6%) | 7 | 0/30 (0%) | 0 |
| Hypertension | 12/58 (20.7%) | 18 | 6/30 (20%) | 6 |
| Hypotension | 4/58 (6.9%) | 5 | 1/30 (3.3%) | 1 |
| Endocrine disorders | ||||
| Hypothyroidism | 8/58 (13.8%) | 9 | 3/30 (10%) | 3 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 3/58 (5.2%) | 3 | 2/30 (6.7%) | 2 |
| Abdominal pain upper | 4/58 (6.9%) | 4 | 3/30 (10%) | 3 |
| Constipation | 7/58 (12.1%) | 7 | 2/30 (6.7%) | 2 |
| Diarrhoea | 14/58 (24.1%) | 23 | 7/30 (23.3%) | 13 |
| Gastritis | 3/58 (5.2%) | 3 | 0/30 (0%) | 0 |
| Gastrooesophageal reflux disease | 3/58 (5.2%) | 8 | 1/30 (3.3%) | 1 |
| Nausea | 14/58 (24.1%) | 21 | 7/30 (23.3%) | 8 |
| Oral pain | 3/58 (5.2%) | 3 | 3/30 (10%) | 3 |
| Stomatitis | 6/58 (10.3%) | 8 | 6/30 (20%) | 10 |
| Vomiting | 14/58 (24.1%) | 21 | 0/30 (0%) | 0 |
| General disorders | ||||
| Asthenia | 11/58 (19%) | 19 | 5/30 (16.7%) | 5 |
| Fatigue | 14/58 (24.1%) | 14 | 8/30 (26.7%) | 11 |
| General physical health deterioration | 3/58 (5.2%) | 3 | 1/30 (3.3%) | 1 |
| Mucosal inflammation | 6/58 (10.3%) | 10 | 1/30 (3.3%) | 1 |
| Pain | 3/58 (5.2%) | 3 | 0/30 (0%) | 0 |
| Pyrexia | 11/58 (19%) | 18 | 4/30 (13.3%) | 6 |
| Hepatobiliary disorders | ||||
| Cholecystitis acute | 0/58 (0%) | 0 | 2/30 (6.7%) | 2 |
| Infections and infestations | ||||
| Pneumonia | 1/58 (1.7%) | 1 | 2/30 (6.7%) | 2 |
| Urinary tract infection | 6/58 (10.3%) | 6 | 2/30 (6.7%) | 2 |
| Nasopharyngitis | 3/58 (5.2%) | 3 | 1/30 (3.3%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Procedural pain | 3/58 (5.2%) | 3 | 3/30 (10%) | 3 |
| Investigations | ||||
| Blood creatinine increased | 6/58 (10.3%) | 9 | 4/30 (13.3%) | 5 |
| Gamma-glutamyltransferase increased | 3/58 (5.2%) | 3 | 0/30 (0%) | 0 |
| Glomerular filtration rate decreased | 3/58 (5.2%) | 3 | 1/30 (3.3%) | 1 |
| Neutrophil count decreased | 4/58 (6.9%) | 5 | 4/30 (13.3%) | 4 |
| Platelet count decreased | 2/58 (3.4%) | 3 | 3/30 (10%) | 4 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 10/58 (17.2%) | 12 | 5/30 (16.7%) | 5 |
| Hypercalcaemia | 4/58 (6.9%) | 6 | 2/30 (6.7%) | 3 |
| Hyperkalaemia | 3/58 (5.2%) | 3 | 0/30 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 5/58 (8.6%) | 5 | 3/30 (10%) | 3 |
| Back pain | 10/58 (17.2%) | 13 | 3/30 (10%) | 3 |
| Musculoskeletal pain | 4/58 (6.9%) | 4 | 0/30 (0%) | 0 |
| Neck pain | 0/58 (0%) | 0 | 2/30 (6.7%) | 2 |
| Pain in extremity | 5/58 (8.6%) | 7 | 2/30 (6.7%) | 2 |
| Pathological fracture | 0/58 (0%) | 0 | 3/30 (10%) | 3 |
| Nervous system disorders | ||||
| Dizziness | 3/58 (5.2%) | 3 | 3/30 (10%) | 4 |
| Dysgeusia | 9/58 (15.5%) | 14 | 5/30 (16.7%) | 7 |
| Headache | 7/58 (12.1%) | 8 | 1/30 (3.3%) | 1 |
| Paresis | 1/58 (1.7%) | 1 | 2/30 (6.7%) | 2 |
| Psychiatric disorders | ||||
| Anxiety | 5/58 (8.6%) | 6 | 0/30 (0%) | 0 |
| Renal and urinary disorders | ||||
| Haematuria | 3/58 (5.2%) | 3 | 0/30 (0%) | 0 |
| Renal failure | 3/58 (5.2%) | 3 | 4/30 (13.3%) | 4 |
| Renal impairment | 2/58 (3.4%) | 3 | 2/30 (6.7%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 4/58 (6.9%) | 4 | 1/30 (3.3%) | 1 |
| Dyspnoea | 4/58 (6.9%) | 4 | 2/30 (6.7%) | 2 |
| Epistaxis | 5/58 (8.6%) | 8 | 2/30 (6.7%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Dry skin | 4/58 (6.9%) | 4 | 2/30 (6.7%) | 2 |
| Palmar-plantar erythrodysaesthesia syndrome | 7/58 (12.1%) | 8 | 3/30 (10%) | 3 |
| Pruritus | 3/58 (5.2%) | 4 | 0/30 (0%) | 0 |
| Rash | 3/58 (5.2%) | 4 | 1/30 (3.3%) | 1 |
Limitations/Caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Immunicum Aktiebolag (AB) |
| Phone | +46 (0)8 732 84 00 |
| info@immunicum.com |
Responsible Party:
Immunicum AB
ClinicalTrials.gov Identifier:
NCT02432846
Other Study ID Numbers:
- IM-201
- 2014-004510-28
First Posted:
May 4, 2015
Last Update Posted:
Aug 22, 2022
Last Verified:
Jul 1, 2022