Clinical Trial Results:
A phase 2, open-label, single-arm, multicenter study to evaluate the efficacy and safety of SOT101 in combination with cetuximab in patients with RAS wild-type colorectal cancer (AURELIO-05)
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Summary
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EudraCT number |
2022-001527-32 |
Trial protocol |
ES BE IT FR |
Global end of trial date |
03 Jun 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
30 May 2025
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First version publication date |
30 May 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SC105 (AURELIO-05)
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05619172 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND number: 140011 | ||
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Sponsors
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Sponsor organisation name |
SOTIO Biotech AG
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Sponsor organisation address |
Lichtstrasse 35 - WSJ-210, Basel, Switzerland, 4056
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Public contact |
Clinical trials, SOTIO Biotech AG, +420 224 175 111, clinicaltrial@sotio.com
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Scientific contact |
Clinical trials, SOTIO Biotech AG, +420 224 175 111, clinicaltrial@sotio.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Jun 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Jun 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Jun 2024
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To estimate the antitumor efficacy of nanrilkefusp alfa in combination with cetuximab
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Protection of trial subjects |
Not applicable
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Background therapy |
Cetuximab was administered on day 1 (from cycle 2 onwards, ±1 day), day 8 (±1 day), and day 15 (±1 day) of each 21-day cycle. The initial dose of cetuximab was 400 mg/m2 body surface area administered as intravenous infusion over 120 minutes. All subsequent weekly doses were 250 mg/m2 each administered as intravenous infusion over 60 minutes. Patients may have been premedicated with an antihistamine and a corticosteroid at least 1 hour before cetuximab administration. On day 1 and day 8, cetuximab infusion started within 30 minutes after nanrilkefusp alfa administration. | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
22 Dec 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 6
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Country: Number of subjects enrolled |
Belgium: 7
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Country: Number of subjects enrolled |
France: 3
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Worldwide total number of subjects |
16
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EEA total number of subjects |
16
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
11
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
Not applicable | ||||||
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Pre-assignment
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Screening details |
Eight investigational sites participated in study SC105 and screened at least 1 patient (2 sites in France, 4 sites in Spain, and 2 sites in Belgium). | ||||||
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Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Nanrilkefusp alfa combined with cetuximab | ||||||
Arm description |
- | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Nanrilkefusp alfa
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Investigational medicinal product code |
SOT101
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Other name |
SO-C101, RLI-15
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Pharmaceutical forms |
Solution for injection in vial
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Nanrilkefusp alfa was administered subcutaneously on day 1 (from cycle 2 onwards, ±1 day), day 2 (±1 day), day 8 (±1 day), and day 9 (±1 day) of each 21-day cycle. The dose of nanrilkefusp alfa for the main cohort of the study was determined in the initial 3+3 safety cohorts.
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Baseline characteristics reporting groups
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Reporting group title |
Overall (overall period)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
All-subjects-as-treated population
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The all-subjects-as-treated (ASaT) population consisted of all patients exposed to nanrilkefusp alfa or cetuximab. All safety analyses and selected efficacy analyses were performed on the ASaT population.
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End points reporting groups
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Reporting group title |
Nanrilkefusp alfa combined with cetuximab
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Reporting group description |
- | ||
Subject analysis set title |
All-subjects-as-treated population
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
The all-subjects-as-treated (ASaT) population consisted of all patients exposed to nanrilkefusp alfa or cetuximab. All safety analyses and selected efficacy analyses were performed on the ASaT population.
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End point title |
Objective response rate according to RECIST 1.1 [1] | ||||||||
End point description |
Objective response rate according to RECIST 1.1 was defined as the proportion of patients with complete response according to RECIST 1.1 or partial response according to RECIST 1.1. Patients with missing data were considered non-responders.
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End point type |
Primary
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End point timeframe |
Day 1 up to approximately 3 years
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this end point. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Objective response rate according to iRECIST | ||||||||
End point description |
Objective response rate according to iRECIST was defined as the proportion of patients with complete response according to iRECIST or partial response according to iRECIST. Patients with missing data were considered non-responders.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Best overall response according to RECIST 1.1: complete response | ||||||
End point description |
The best overall response according to RECIST 1.1 was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy. Stable disease according to RECIST 1.1 had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Best overall response according to RECIST 1.1: partial response | ||||||
End point description |
The best overall response according to RECIST 1.1 was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy. Stable disease according to RECIST 1.1 had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Best overall response according to RECIST 1.1: stable disease | ||||||
End point description |
The best overall response according to RECIST 1.1 was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy. Stable disease according to RECIST 1.1 had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Best overall response according to RECIST 1.1: progressive disease | ||||||
End point description |
The best overall response according to RECIST 1.1 was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy. Stable disease according to RECIST 1.1 had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Best overall response according to iRECIST: complete response | ||||||
End point description |
The best overall response according to iRECIST was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy. Stable disease according to iRECIST had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Best overall response according to iRECIST: partial response | ||||||
End point description |
The best overall response according to iRECIST was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy. Stable disease according to iRECIST had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Best overall response according to iRECIST: stable disease | ||||||
End point description |
The best overall response according to iRECIST was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy. Stable disease according to iRECIST had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Best overall response according to iRECIST: unconfirmed progressive disease | ||||||
End point description |
The best overall response according to iRECIST was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy. Stable disease according to iRECIST had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Best overall response according to iRECIST: confirmed progressive disease | ||||||
End point description |
The best overall response according to iRECIST was defined as the best response from the start of study treatment until the first documented disease progression, death, or start of new anti-cancer therapy. Stable disease according to iRECIST had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Duration of response according to RECIST 1.1 | ||||||||
End point description |
Duration of response according to RECIST 1.1 was defined as time to disease progression for patients with partial response or complete response according to RECIST 1.1.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of response according to iRECIST | ||||||||
End point description |
Duration of response according to iRECIST was defined as time to disease progression for patients with partial response or complete response according to iRECIST.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Clinical benefit rate according to RECIST 1.1 | ||||||||
End point description |
Clinical benefit rate according to RECIST 1.1 was defined as the number of partial responses, complete responses, and stable disease according to RECIST 1.1. Stable disease had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease. Patients with missing data were considered non-responders.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Clinical benefit rate according to iRECIST | ||||||||
End point description |
Clinical benefit rate according to iRECIST was defined as the number of partial responses, complete responses, and stable disease according to iRECIST. Stable disease had to last at least 6 weeks from the start of study treatment. If not, at least 1 follow-up scan was required to declare stable disease. Patients with missing data were considered non-responders.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free survival according to RECIST 1.1 | ||||||||
End point description |
Progression-free survival according to RECIST 1.1 was defined as the time from the first day of study treatment to the first date of radiological disease progression according to RECIST 1.1 or death.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free survival according to iRECIST | ||||||||
End point description |
Progression-free survival according to iRECIST was defined as the time from the first day of study treatment to the first date of radiological disease progression according to iRECIST or death.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to response according to RECIST 1.1 | ||||||||
End point description |
Time to response according to RECIST 1.1 was defined as the time from the first day of study treatment to the first date of partial response or complete response according to RECIST 1.1. Patients with missing data were censored at the last assessment date, date of death, or date of eligibility (for incomplete or missing baseline tumor assessments), whichever occurred last.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to response according to iRECIST | ||||||||
End point description |
Time to response according to iRECIST was defined as the time from the first day of study treatment to the first date of partial response or complete response according to iRECIST. Patients with missing data were censored at the last assessment date, date of death, or date of eligibility (for incomplete or missing baseline tumor assessments), whichever occurred last.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to progression according to RECIST 1.1 | ||||||||
End point description |
Time to progression according to RECIST 1.1 was defined as the time from the first day of study treatment to the first date of radiological disease progression according to RECIST 1.1.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to progression according to iRECIST | ||||||||
End point description |
Time to progression according to iRECIST was defined as the time from the first day of study treatment to the first date of radiological disease progression according to iRECIST.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of patients with treatment-emergent adverse events | ||||||
End point description |
A treatment-emergent adverse event was defined as an adverse event that started or worsened at or after the start of study treatment.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Number of patients with clinical laboratory test abnormalities | ||||||
End point description |
The following laboratory parameters were assessed:
Coagulation: prothrombin time, activated partial thromboplastin time, international normalized ratio, D-dimer, and fibrinogen
Hematology: hemoglobin, hematocrit, red blood cell count, reticulocytes, white blood cell count (with full differentiation), absolute lymphocyte count, and platelet count
Clinical chemistry: Na, K, Cl, phosphate, Mg, Ca, albumin, total protein, ALT, AST, bilirubin (direct, total), alkaline phosphatase, lactate dehydrogenase, creatinine clearance calculated by the Cockcroft-Gault formula, creatinine, glucose (preferably fasting), urea or blood urea nitrogen, cholesterol, triglyceride, C-reactive protein, uric acid, amylase, and lipase
Urinalysis: pH, glucose, protein, bilirubin, urobilinogen. Microscopic examination (mandated only if clinically indicated): red blood cell count, white blood cell count, epithelial cells, bacteria
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Number of patients with vital signs abnormalities | ||||||
End point description |
The following vital signs parameters were assessed: Blood pressure (systolic and diastolic, after ≥5 minutes of rest), body temperature, and heart rate
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Number of patients with electrocardiography abnormalities | ||||||
End point description |
Standard 12-lead electrocardiography was evaluated locally.
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End point type |
Secondary
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End point timeframe |
Day 1 up to approximately 3 years
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| No statistical analyses for this end point | |||||||
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End point title |
Number of patients with dose-limiting toxicities | ||||||
End point description |
The following adverse events as per NCI CTCAE version 5.0 were considered dose-limiting toxicities:
- All grade 5 events not clearly related to disease progression or any other causes
- Any grade 3 or higher non-hematologic toxicity regardless of duration; exceptions:
-- Grade 3 nausea, vomiting, or diarrhea that could be controlled within 72 hours
-- Grade 3 fatigue lasting less than 5 days
-- Grade 3 or higher correctable electrolyte abnormalities lasting less than 72 hours and not associated with clinical complications
-- Grade 3 or higher serum amylase or lipase not associated with clinical manifestations of pancreatitis
-- Grade 3 AST or ALT increase or grade 3 blood bilirubin increase lasting 5 days or less
- Hy's law cases
- Hematologic DLTs:
-- Grade 4 decreased neutrophil count or decreased platelet count lasting more than 7 days
-- Febrile neutropenia
-- Grade 3 or higher decreased platelet count with bleeding
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End point type |
Secondary
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End point timeframe |
Through Cycle 1 (21 days)
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| No statistical analyses for this end point | |||||||
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End point title |
Area under the curve of nanrilkefusp alfa | ||||||||
End point description |
At 9 µg/kg nanrilkefusp alfa, over the last measurable timepoint
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End point type |
Secondary
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End point timeframe |
Day 1 of Cycle 1
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum concentration of nanrilkefusp alfa | ||||||||
End point description |
At 9 µg/kg nanrilkefusp alfa
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End point type |
Secondary
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End point timeframe |
Day 1 of Cycle 1
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to maximum concentration of nanrilkefusp alfa | ||||||||
End point description |
At 9 µg/kg nanrilkefusp alfa
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End point type |
Secondary
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End point timeframe |
Day 1 of Cycle 1
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| No statistical analyses for this end point | |||||||||
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End point title |
Pre-dose concentration of nanrilkefusp alfa | ||||||||
End point description |
At 9 µg/kg nanrilkefusp alfa
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End point type |
Secondary
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End point timeframe |
Day 1 of Cycle 1
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| No statistical analyses for this end point | |||||||||
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End point title |
Incidence of treatment-induced anti-drug antibodies against nanrilkefusp alfa | ||||||
End point description |
At 9 µg/kg and 12 µg/kg nanrilkefusp alfa
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End point type |
Secondary
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End point timeframe |
Day 1 until 30 (±2) days after the last dose of nanrilkefusp alfa
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events: from the start to 90 days after the end of study treatment; related serious adverse events: collected beyond 90 days after the end of study treatment; deaths: consent signature to study end
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Adverse event reporting additional description |
Only treatment-emergent adverse events were analyzed (see the definition above); the tables include information on treatment-emergent adverse events, serious treatment-emergent adverse events, and all deaths; causality was assessed by investigators
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
Nanrilkefusp alfa combined with cetuximab
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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09 Mar 2023 |
- Addition of a urine pregnancy test to the End of treatment visit and in the Follow-up
- Timing of body weight assessment used for calculation of dose clarified to be made within 3 days prior to day 1
- Addition of ECG assessment to day 1 of each cycle and End of treatment visit
- Allowed visit window for safety laboratory samples adjusted
- Collection of samples for ADA determination in the treatment phase limited to cycles 2, 3 and 4
- Initial tumor scans can be taken with a visit window of 21 days before ICF signature
- PK sampling schedule adjusted
- Benefit/risk assessment updated
- PK and immunogenicity of cetuximab are to be determined as an exploratory endpoint
- Inclusion criterion 5 was modified, and criterion no. 6 was added with specification of tests to be used for confirmation of RAS wild type
- Inclusion criterion 6 on EGFR mutation status availability was removed, information on status determination added into another section
- Exclusion criterion 4 added to specify allowed lines of previous therapy to four
- Addition of management recommendations for cytokine release syndrome, shortening of the QT interval, increased ALT and/or AST, and injection site reaction
- Guidance added on additional diagnostic measurements for patients with pre-existing pulmonary diseases and/or presence or suspicion of ILD and for patients with ophthalmological pre-conditions
- Clarification added that safety assessments are to be done by local laboratories
- Hy’s law added and referred to in appendix 3
- Cockcroft-Gault formula added and referred to in appendix 4
- Sample size of patients specified to include patients from the safety cohorts and the main cohort
- Change of “SOT101” to “nanrilkefusp alfa in Protocol body |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
