Clinical Trial Results:
A Two-Part, Open-Label Phase 1/2 Study to Evaluate Pharmacodynamic Effects and Safety of Olaptesed Pegol Monotherapy and Safety and Efficacy of Olaptesed Pegol / Pembrolizumab Combination Therapy in Metastatic Colorectal and Pancreatic Cancer
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Summary
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EudraCT number |
2016-003657-15 |
Trial protocol |
DE |
Global end of trial date |
25 Mar 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Apr 2021
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First version publication date |
08 Apr 2021
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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 |
SNOXA12C601
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03168139 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Keynote: 559 | ||
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Sponsors
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Sponsor organisation name |
NOXXON Pharma AG
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Sponsor organisation address |
Max-Dohrn-Strasse 8-10, Berlin, Germany, 10589
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Public contact |
Clinical Trial Disclosure Desk NOXXON, NOXXON Pharma AG, +49 30726247100, clinicaltrialdisclosuredesk@noxxon.com
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Scientific contact |
Clinical Trial Disclosure Desk NOXXON, NOXXON Pharma AG, +49 30726247100, clinicaltrialdisclosuredesk@noxxon.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 |
02 Oct 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
25 Mar 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Mar 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Monotherapy part:
Pharmacodynamics – evaluation of immune infiltrate changes within the tumor microenvironment induced by CXCL12 inhibition with olaptesed pegol by comparing pre- and post-treatment biopsy specimens
Combination therapy part:
To assess safety and tolerability of olaptesed pegol in combination with pembrolizumab
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Protection of trial subjects |
This clinical study was written, conducted and reported in accordance with the protocol, ICH GCP Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, 2005/28/EC, and 2003/63/EC and relevant national and local legislations, and with the ethical principles that have their origin in the Declaration of Helsinki. Only subjects that met all the study inclusion and none of the exclusion criteria were randomized. Study drug administrations were performed by qualified and trained study personnel. Patient who received treatment were closely followed by means of adverse event reporting and vital signs. In the event of a study related adverse event, patients were monitored to determine the outcome. The clinical course of the AE was followed up according to accepted standards of medical practice, even after the end of the period of observation, until a satisfactory explanation is found or the Investigator considered it medically justifiable to terminate follow-up.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 May 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Germany: 20
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Worldwide total number of subjects |
20
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EEA total number of subjects |
20
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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) |
9
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
24 patients with diagnosis metastatic colorectal or metastatic pancreatic cancer were screened; 4 patients were screening failure. After a screening period of 4 weeks 20 patients were enrolled. | ||||||||||||
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Pre-assignment
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Screening details |
24 patients with diagnosis metastatic colorectal or metastatic pancreatic cancer were screened; 4 patients were screening failure. After a screening period of 4 weeks 20 patients were enrolled. | ||||||||||||
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Period 1
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Period 1 title |
Overall trial (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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Olaptesed pegol + pembrolizumab | ||||||||||||
Arm description |
- | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Olaptesed pegol
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Investigational medicinal product code |
NOX-A12
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Monotherapy (MT): Weekly on MT D1 and MT D4 for up to 2 weeks: administration of 300 mg olaptesed pegol
Combination therapy (CT): Treatment with olaptesed pegol in combination with pembrolizumab until progressive disease or limiting toxicity, for a maximum of 24 months in total CT D1 and every three weeks (Q3W) thereafter: 300 mg olaptesed pegol + 200 mg pembrolizumab
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Investigational medicinal product name |
Pembrolizumab
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Investigational medicinal product code |
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Other name |
MK-3475, Keytruda
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Monotherapy (MT): Weekly on MT D1 and MT D4 for up to 2 weeks: administration of 300 mg olaptesed pegol
Combination therapy (CT): Treatment with olaptesed pegol in combination with pembrolizumab until progressive diseaseor limiting toxicity, for a maximum of 24 months in total CT D1 and every three weeks (Q3W) thereafter: 300 mg olaptesed pegol + 200 mg pembrolizumab
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Olaptesed pegol + pembrolizumab
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Reporting group description |
- | ||
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End point title |
Safety Adverse Events [1] | ||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
AEs and SAEs were collected from the time the patient gave informed consent until 30 days after the last olaptesed pegol and pembrolizumab dose for non-serious AEs and until 90 days for SAEs
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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 endpoint. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Safety Dose Limiting Toxicities [2] | ||||||||
End point description |
DLTs were defined as
• Grade 4 non-hematologic AEs (not laboratory)
• Grade 4 hematologic AE lasting >7d, except thrombocytopenia <25,000/mm³ if associated with bleeding event which does not result in hemodynamic instability but requires an elective platelet transfusion, or life-threatening bleeding event which results in urgent intervention and admission to an ICU
• Grade 3 non-hematologic AE (not laboratory) lasting >3d
• Grade 3 nausea, vomiting or diarrhea if lasting >3d
• Grade 3 or Grade 4 non-hematologic laboratory AE, if medical intervention is required, or to hospitalization, or persists for > 1 week
• Grade 3 or Grade 4 febrile neutropenia
• Grade 5 AE
• AE which caused treatment discontinuation during Cycle 1
• Any AE which delayed initiation of Cycle 2 by >2 weeks
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End point type |
Primary
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End point timeframe |
The period of evaluating DLT was throughout the monotherapy and one 21-day cycle of the combination therapy.
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| Notes [2] - 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 endpoint |
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Adverse events information
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Timeframe for reporting adverse events |
From time the patient gives informed consent until 30 days after the last NOX-A12 administration
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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 |
21.1
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Reporting groups
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Reporting group title |
Olaptesed pegol + pembrolizumab
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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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Date |
Amendment |
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09 Mar 2017 |
Amendment 1
prepared to comply with the requirements from BfArM and EC during the initial submission.;
Changes to the protocol:
Addition of most current treatments in inclusion criteria;
Update of several exclusion criteria;
Added HIV test at screening;
Enlarged benefit / risk assessment;
Added definition on completion of study;
Complete restructuring of section ‘selection of doses’;
Reworked amended the following sections ‘selection of study population’, ‘patient withdrawal’, ‘contraception’, ‘pharmacodynamics’, ‘pharmacokinetics’, ‘pharmacogenetics’, ‘immunogenicity’, ‘patient information and consent’;
Added Reference Safety Information from the current IB
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02 May 2017 |
Amendment 2
Changes requested by MSD on the approved version 1.1;
Update of benefit / risk assessment;
Changed MSI / MSS status determination to mandatory for PaC patients
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29 Aug 2017 |
Amendment 3
Added clarifications to inclusion criterion and to the order of assessment in the flow chart
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21 Dec 2017 |
Amendment 4
Added clarifications to the flow chart and ECG parameters recorded
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21 Sep 2018 |
Amendment 5
Added collection of additional data during follow-up and to included information about the occurrence of cancer in the family history in medical history
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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 | |||
