First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer - prospective, multicentre, phase II trial

Sep 22, 2026

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Metastatic pancreatic cancer shows poor prognosis. This prospective, multicentre, single-arm phase II trial evaluated the efficacy and safety of penpulimab plus anlotinib combined with nab-paclitaxel/gemcitabine (PAAG) as first-line therapy in patients with metastatic pancreatic cancer (NCT05493995). Primary endpoints were objective response rate and disease control rate; secondary endpoints included progression-free survival, overall survival, and safety. Among 66 efficacy-evaluable patients, ORR was 50.0% and DCR 95.5%, with median PFS 8.8 months and OS 13.7 months. Grade 3/4 treatment-related adverse events occurred in 39.4%. Exploratory biomarker analyses suggested links between genomic/immune features and improved outcomes, and the regimen showed tolerability with promising clinical efficacy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Background on metastatic pancreatic cancer and current therapies

Rationale for combining immunotherapy and antiangiogenic treatment

Trial design and endpoints

Primary endpoints and efficacy outcomes

Secondary endpoints and safety assessment

Results and exploratory biomarker findings

Best response, DCR, PFS, and OS

Treatment-related adverse events

Biomarkers associated with efficacy

Signal Transduction [and Targeted Therapy](and Targeted Therapy www.nature.com/sigtrans)[ www.nature.com/sigtrans](and Targeted Therapy www.nature.com/sigtrans) First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial Huizi Sha1, Fan Tong2, Jiayao Ni2, Yi Sun 1, Yahui Zhu1, Liang Qi1, Xiaoqin Li3, Wei Li4, Yan Yang5, Qing Gu6, Xing Zhang7, Xiaoxuan Wang7, Chan Zhu7, Dongsheng Chen7, Baorui Liu1 ✉ and Juan Du 1,2 ✉ | | Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efﬁcacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) inpatients with ﬁrst-line mPC (NCT05493995) . The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efﬁcacy, the best response, indicated by the ORR, was recorded at 50.0%(33/66) (95% CI, 37.4–62.6%), with 33 patients achieving partial response (PR) . Notably, the DCR was 95.5%(63/66, 95% CI, 87.3–99.1%) . The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1–11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66) . In prespeciﬁed exploratory analysis, patients with altered SWI/SNF complex hada poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efﬁcacy. In conclusion, PAAG as a ﬁrst-line therapy demonstrated tolerability with promising clinical efﬁcacy for mPC. The biomolecular ﬁndings identiﬁed in this study possess the | | | --- | --- | --- | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | potential to guide the precise clinical application of the triple-combo regimen. | | | | | Signal Transduction and Targeted Therapy (2024)9:143 ; [https://doi.org/10.1038/s41392-024-01857-6](https://doi.org/10.1038/s41392-024-01857-6) | | | | | | INTRODUCTION Pancreatic cancer (PC), a common malignant tumor of the digestive system, has shown a gradual increase in incidence and mortality worldwide. It is estimated that PC will become the second leading cause of cancer-related deaths worldwide by the year 2030 .1 Currently, systemic chemotherapy remains the cornerstone of treatment for advanced metastatic PC (mPC) . Both the AG regimen (nab-paclitaxel/gemcitabine) and FOLFIRINOX regimen (oxaliplatin + irinotecan + calcium folinate + 5-FU) have objective response rates (ORR) of approximately 20%, and overall survival (OS) does not exceed one year.2,3 While immune checkpoint inhibitors (ICIs) have transformed cancer treatment in the last decade, their clinical beneﬁts in PC remain to be substantiated. Both the CISPD3 study4 (NCT03977272) and the PRINCE study5 (NCT03214250) suggest that the combination of chemotherapy and ICI in PC can improve the ORR, reaching~50% . This indicates that the combination of immunotherapy and chemotherapy has certain potential clinical signiﬁcance. However, the key challenge for future research lies in translating the ORR beneﬁt into improvements in OS and progression-free survival (PFS) . The interaction between the activation of angiogenic signalling pathways and the suppression of tumor immunity has been validated. Remarkably, antiangiogenic drugs, through direct inhibition of tumor growth and metastasis, can reprogram the tumor microenvironment from an immunosuppressive state to permissiveness.6 For instance, patients with advanced intrahepatic cholangiocarcinoma (ICC

FAQs

What treatment combination was evaluated in the phase II trial?

The study evaluated penpulimab plus anlotinib combined with nab-paclitaxel/gemcitabine (PAAG) as first-line therapy for metastatic pancreatic cancer.

Which endpoints were used to assess efficacy and safety?

Primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety, including grade 3/4 treatment-related adverse events.

What were the key efficacy and safety results?

Among 66 efficacy-evaluable patients, ORR was 50.0% and DCR was 95.5%. Median PFS was 8.8 months and median OS was 13.7 months; grade 3/4 treatment-related adverse events occurred in 39.4% of patients.

Sep 22, 2026

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