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. 2024 Dec;12(4):817-831.
doi: 10.1007/s40487-024-00309-z. Epub 2024 Oct 23.

Stereotactic Radiotherapy Plus Nivolumab in Patients with Locally Advanced Pancreatic Cancer: Results from Phase 1/2 Clinical CA209-9KH Trial

Milan Vošmik  1   2 , Stanislav John  3   4 , Josef Dvořák  5   6 , Beatrice Mohelníková-Duchoňová  7   8 , Bohuslav Melichar  7   8 , Radka Lohynská  5   6 , Aleš Ryška  4   9 , Aml Mustafa Banni  3   4 , Johana Krempová  3 , Igor Sirák  3   4
Affiliations

Stereotactic Radiotherapy Plus Nivolumab in Patients with Locally Advanced Pancreatic Cancer: Results from Phase 1/2 Clinical CA209-9KH Trial

Milan Vošmik et al. Oncol Ther. 2024 Dec.

Abstract

Introduction: The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) highlights the urgent need for novel therapeutic strategies. Immune checkpoint inhibitors (ICIs) seem to be ineffective in most PDAC studies. Therefore, we conducted an open-label, multicenter phase 1/2 study (CA209-9KH) to evaluate the safety of stereotactic radiotherapy (SRT) and sequential ICI therapy in PDAC, as well as to validate the efficacy of this regimen as a potential activator of antitumor immunity.

Methods: Patients aged ≥ 18 years with unresectable non-metastatic PDAC following four FOLFIRINOX induction cycles were included. Treatment comprised SRT (4 × 8 Gy) and sequential nivolumab administration until disease progression or unacceptable toxicity. The primary endpoints were safety and toxicity assessment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), biomarker evaluation, and quality of life (QoL) analysis.

Results: Twenty-two patients were screened, with 15 enrolled. Eleven (median) nivolumab cycles were administered. SRT demonstrated low and clinically nonsignificant toxicity, whereas nivolumab toxicity aligned with prior safety profiles, without grade 4-5 events observed. Three patients discontinued therapy owing to toxicity. Median PFS and OS were 8.1 and 13.0 months, respectively, with 12-month PFS and OS rates of 0% and 66.7%, respectively, and a 24-month OS rate of 8.9%. Biomarker levels correlated with clinical or radiological disease control. Patient-reported QoL remained acceptable, deteriorating with disease progression.

Conclusion: SRT and nivolumab therapy exhibited manageable toxicity profiles consistent with previous findings; however, long-term treatment responses were not achieved with this regimen in locally advanced PDAC. Another strategy to trigger antitumor immunity in PDAC needs to be sought.

Trial registration: EudraCT: 2017-003404-52; ClinicalTrials.gov: NCT04098432.

Keywords: Nivolumab; Pancreatic ductal adenocarcinoma; Stereotactic radiotherapy.

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Conflict of interest statement

Declarations Conflict of Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Milan Vošmik—Consulting and advisory role: Accord, AstraZeneca, BMS, Merck, MSD, Sanofi. Honoraria—scientific presentations: BMS, Eisai, Gilead, Ipsen, MSD, Roche. Travel and accommodation support: BMS, Merck, MSD. Stanislav John—Consulting and advisory role: Servier, BMS, Merck, Amgen, AstraZeneca, Takeda. Honoraria—scientific presentations: Servier, BMS, Merck, Amgen, AstraZeneca. Travel and accommodation support: Servier, BMS, Merck, Amgen, AstraZeneca. Beatrice Mohelníková-Duchoňová—Honoraria—scientific presentations: Servier, AstraZeneca, Merck, Amgen; Travel and accommodation support: Servier, AstraZeneca, Merck, Amgen. Bohuslav Melichar—Honoraria for lectures and advisory boards—Roche, Pfizer, BMS, Astellas, Novartis, MSD, Merck Serono, Servier, AstraZeneca, Eisai, E. Lilly, Pierre Farbre; Travel support—AstraZeneca, BMS, MSD, Merck Serono. Radka Lohynská—Honoraria for lectures, presentations, or educational events—Roche, Janssen, Bristol Myers Squibb, MSD and Merck. Aleš Ryška—Consulting and advisory role: Amgen, AstraZeneca, Roche, BMS, MSD, Gilead, Eli Lilly, Merck Serono, Sanofi, Bayer. Honoraria—scientific presentations: Pfizer, Bayer. Travel and accomodation support: Gilead, Sanofi. Igor Sirák—Consulting and advisory role: GSK, MSD. Travel and accomodation support: Novartis. Ethical Approval The study protocol, informed consents for patients, and all other relevant documents were approved by the Ethics Committee of the University Hospital Hradec Králové (EC UHHK) and the local ethics committees of other participating centers: Ethics Committee of the University Hospital Olomouc and Ethics Committee of the Thomayer University Hospital. The EC UHHK has the approval of the Ministry of Health of the Czech Republic for multicentric clinical trials and is accredited in the USA by the Organization Office for Human Research Protections (number IORG0008813). The trial was conducted in accordance with the Guideline for Good Clinical Practice and the Declaration of Helsinki. All study participants were fully informed and signed informed consent for the study.

Figures

Fig. 1
Fig. 1
Clinical trial design
Fig. 2
Fig. 2
Kaplan–Meier-estimated overall survival curve. CI confidence interval, KM Est Kaplan–Meier estimation
Fig. 3
Fig. 3
Kaplan–Meier-estimated progression-free survival curve. CI confidence interval, KM Est Kaplan–Meier estimation
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