Clinical Trial Results:
Phase IIA trial of short-term chemotherapy and pembrolizumab, followed by Pembrolizumab and Olaparib as firstline therapy in Her-2 negative gastric/gastroesophageal-junction (GEJ) Adenocarcinoma – POLESTAR –
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Summary
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EudraCT number |
2021-000150-26 |
Trial protocol |
DE |
Global end of trial date |
09 Jan 2025
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Mar 2026
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First version publication date |
27 Mar 2026
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Other versions |
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Summary report(s) |
Non-serious AE Listing |
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 |
POLESTAR
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Additional study identifiers
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ISRCTN number |
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US NCT number |
NCT05268510 | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
IKF number: IKF-038, AIO-STO-0121/ass.: AIO | ||
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Sponsors
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Sponsor organisation name |
Frankfurter Institut für Klinische Krebsforschung IKF GmbH
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Sponsor organisation address |
Steinbacher Hohl 2-26, Frankfurt, Germany,
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Public contact |
IKF, Frankfurter Institut für Klinische Krebsforschung IKF GmbH, 0049 69589978719, polestar@ikf-khnw.de
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Scientific contact |
IKF, Frankfurter Institut für Klinische Krebsforschung IKF GmbH, 0049 69589978719, polestar@ikf-khnw.de
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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 |
14 Nov 2025
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Jan 2025
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Jan 2025
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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 |
The primary objective of this study was to assess the efficacy in terms of overall survival rate at one year after enrollment of the chemoimmunotherapy induction followed by pembrolizumab/ olaparib combination therapy in patients with HER2 negative esophagogastric adenocarcinoma.
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Protection of trial subjects |
This clinical study was designed and shall be implemented and reported in accordance with the protocol, the AMG (Arzneimittelgesetz), the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local regulations (including European Directive 2001/20/EC), and with the ethical principles laid down in the Declaration of Helsinki. The trial was authorized/approved by the competent authority (Paul-Ehrlich-Institut, PEI) and the competent ethics committee responsible for the trial. Before recruitment into the clinical trial, each patient was informed that participation in the study is completely voluntary, and that he or she may withdraw his or her participation in the trial at any time without any declaration of reasons, which will not lead to any disadvantage for the respective patient. The eligibility of a new patient was determined by the local investigator during regular clinical visits. The examinations for the study and the inclusion of the patient were done after detailed written and oral education about aims, methods, anticipated benefits and potential hazards of the study by use of the informed consent forms and after given written consent of the patient. Safety was monitored continuously by careful monitoring of all adverse events (AEs) and serious adverse events (SAEs) reported.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Sep 2022
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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: 31
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Worldwide total number of subjects |
31
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EEA total number of subjects |
31
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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) |
18
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From 65 to 84 years |
13
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited by the investigator during regular clinical visits in registered trial sites. Recruitment to the study started on September 5th, 2022 and ended on Januar 10th, 2023. A total of 32 patients was screened and 31 patients from a total of 8 different study sites were enrolled | ||||||||||||||||
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Pre-assignment
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Screening details |
Eligible patients were ≥18years, had histologically confirmed metastatic or unresectable, HER2 negative gastroesophagal adenocarcinoma and ECOG 0-1, who did not receive prior systemic anti-cancer therapy for metastatic or locally advanced (irresectable) disease and any treatment with immune checkpoint inhibitor and PARP inhibitor | ||||||||||||||||
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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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Experimental | ||||||||||||||||
Arm description |
Patients received two 6-weeks cycles (Q6W) of induction chemoimmunotherapy (mFOLFOX-6 or CAPOX according to investigators’ decision plus pembrolizumab) followed by consolidation therapy consisting of combination of pembrolizumab plus olaparib for up to 16 cycles (total 18 cycles). | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
Pembrolizumab
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Investigational medicinal product code |
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Other name |
Keytruda
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Pembrolizumab at a fixed dose of 400 mg was administered as an IV infusion. During chemotherapy, pembrolizumab was administered prior to chemotherapy on day 1 of the first and second cycle. Following the chemoimmunotherapy pembrolizumab was administered every 6 weeks starting on day 1 of each pembrolizumab plus olaparib cycle
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Investigational medicinal product name |
Olaparib
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Investigational medicinal product code |
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Other name |
LYNPARZA
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Olaparib was administered at a dose of 300 mg orally twice daily continuously starting on day 1 of the first pembrolizumab plus olaparib cycle
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Investigational medicinal product name |
mFOLFOX
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Investigational medicinal product code |
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Other name |
oxaliplatin, leucovorin/sodium folinate, 5-fluorouracil
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous bolus use , Intravenous use
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Dosage and administration details |
The modified FOLFOX6 chemotherapy was administered on day 1, 15 and 29 (on day 1 after the 30-minute pembrolizumab IV infusion) starting with oxaliplatin 85 mg/m² as a 2 hours IV infusion, followed by leucovorin/sodium folinate 400 mg/m² as a 2 hours IV infusion, followed by 5-FU 400 mg/m² as bolus (2-5 minutes) and 5-FU 2,400 mg/m² applied in 46 h.
Patients received modified FOLFOX6 OR CAPOX regimen according to clinical standard and investigators’ decision!
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Investigational medicinal product name |
CAPOX
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Investigational medicinal product code |
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Other name |
oxaliplatin, capecitabine
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Pharmaceutical forms |
Concentrate for solution for infusion, Film-coated tablet
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Routes of administration |
Intravenous use, Oral use
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Dosage and administration details |
The CAPOX chemotherapy was administered on day 1 and 22 (on day 1 after the 30-minute pembrolizumab IV infusion) with oxaliplatin 130 mg/m² as a 2 hours IV infusion. Capecitabine was taken p.o. at 1,000 mg/m2 bid. on day 1 to day 14 and day 22 to day 35
Patients received modified FOLFOX6 OR CAPOX regimen according to clinical standard and investigators’ decision!
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Baseline characteristics reporting groups
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Reporting group title |
Experimental
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Reporting group description |
Patients received two 6-weeks cycles (Q6W) of induction chemoimmunotherapy (mFOLFOX-6 or CAPOX according to investigators’ decision plus pembrolizumab) followed by consolidation therapy consisting of combination of pembrolizumab plus olaparib for up to 16 cycles (total 18 cycles). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Experimental
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Reporting group description |
Patients received two 6-weeks cycles (Q6W) of induction chemoimmunotherapy (mFOLFOX-6 or CAPOX according to investigators’ decision plus pembrolizumab) followed by consolidation therapy consisting of combination of pembrolizumab plus olaparib for up to 16 cycles (total 18 cycles). | ||
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End point title |
Overall survival rate at 12 months (OS@12) [1] | ||||||||||
End point description |
Overall survival rate at 12 months is defined as percentage of patients who remain alive one year after enrollment
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End point type |
Primary
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End point timeframe |
at 12 months after enrollment
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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: As a single‑stage Fleming phase II design was used, efficacy was assessed via a predefined decision rule for the 1‑year survival rate rather than by p‑value calculation |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Overall survival | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
time from enrollment until date of death due to any cause
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| No statistical analyses for this end point | |||||||||||
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End point title |
Progression-free survival | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
time from enrollment untl date of disease progression acc. to RECIST 1.1 or death due to any cause
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| No statistical analyses for this end point | |||||||||||
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End point title |
Best response acc. to RECIST 1.1 | ||||||||||||||||||
End point description |
non-CR/non-PD - corresponding to patients with non-target lesions
Missing - patient discontinued without restaging
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End point type |
Secondary
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End point timeframe |
from enrollement to treatment discontinuation
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Overall response rate (ORR) | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from enrollment until treatment discontinuation
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| No statistical analyses for this end point | |||||||||||
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End point title |
Time to tumor progression | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
from enrollment until time of disease progression acc. to RECIST 1.1
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| No statistical analyses for this end point | |||||||||||
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End point title |
Feasibility rate | ||||||||||
End point description |
defined as 1 – severe toxicity/withdrawal rate before the fourth cycle of pembrolizumab/olaparib has been completed
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End point type |
Secondary
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End point timeframe |
until end of the 4th cycle of pembrolizumab/olaparib
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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 |
AEs - from time of informed consent signing until 30 days after last dose of study treatment
SAEs - from time of informed consent signing until 110 days after last dose of study treatment (or until start of new anti-cancer treatment)
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Adverse event reporting additional description |
Listed here are all serious adverse events and the most common non-serious adverse events, which occurred in ≥ 20% of the patients.
A detailed listing of all non-serious adverse events which occurred in ≥ 5% of the patients is attached as pdf file (summary attachment)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
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Reporting groups
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Reporting group title |
Overall
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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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24 Oct 2024 |
Change of the definition of study end from database closure to Last Patient Last Visit, which corresponds to the common definition |
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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 | |||
