Anniko (penpulimab-kcqx) / Akesobio, Sino Biopharm, Specialised Therap - LARVOL DELTA

Integrated penpulimab (a PD-1 inhibitor), anlotinib (an antiangiogenic targeted drug), nab-paclitaxel and gemcitabine as first-line regimen for metastatic pancreatic cancer: A multi-centered, randomized controlled trial (RCT-PAAG). (ASCO-GI 2026) - P2 | "The integrated regimen involving Penpulimab, Anlotinib, Nab-Paclitaxel and Gemcitabine appears to be a more preferable choice than Gemcitabine-based chemotherapy alone for the first-line treatment of mPC on account of its improved efficacy and acceptable safety. Future follow-up is warranted in confirmation of its impact on OS."

Clinical • IO biomarker • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Immune checkpoint inhibitor-related cholangitis and pancreatitis induced by penpulimab: a case report. (PubMed, AME Case Rep) - "We present findings of cholangitis and pancreatitis linked to the antitumor application of penpulimab, an innovative immunosuppressant. This case provides significant Reference for the diagnosis and management of adverse complications associated with immunotherapy."

Checkpoint inhibition • Journal • Gastric Cancer • Oncology • Pancreatic Cancer • Pancreatitis • Solid Tumor

Penpulimab combined with rituximab, high-dose methotrexate, and cytarabine (Pen-RMA) in newly diagnosed primary central nervous system lymphoma (PCNSL): a phase 2 trial. (PubMed, Blood Cancer J) - P2 | "Among them, 8 had CSF ctDNA clearance while 6 were positive. Overall, Pen-RMA regimen demonstrated encouraging antitumor activity with a manageable toxicity in PCNSL."

Journal • P2 data • CNS Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Primary Central Nervous System Lymphoma • Thrombocytopenia • Transplantation

Penpulimab versus placebo in combination with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A global, multicenter, randomized, double-blind, phase 3 trial (AK105-304) (AACR 2025) - P3 | "Penpulimab combined with gemcitabine and cisplatin or carboplatin demonstrated statistically significant and clinically meaningful benefit with a manageable safety profile, and provides a new beneficial treatment option in the first-line treatment for R/M NPC patients globally."

Clinical • Combination therapy • Metastases • P3 data • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

Anlotinib plus penpulimab versus sorafenib in the first-line treatment of unresectable hepatocellular carcinoma (APOLLO): a randomised, controlled, phase 3 trial. (PubMed, Lancet Oncol) - P3 | "Anlotinib plus penpulimab significantly improved progression-free survival and overall survival versus sorafenib in unresectable HCC and might be a new first-line option. These findings require verification in other regions of the world."

Journal • P3 data • Cardiovascular • Hepatocellular Cancer • Hepatology • Hypertension • Liver Failure • Oncology • Solid Tumor • AFP

A Phase II Clinical Trial of Anti-EGFR Antibody-drug Conjugate (ADC) Combined With or Without Immune Checkpoint Inhibitors in the Neoadjuvant Treatment of Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: West China Hospital

Checkpoint inhibition • New P2 trial • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Penpulimab in combination with lenalidomide and R-GemOx regimen (R2-GemOx-PD1i) in relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm, phase 2 trial. (PubMed, BMC Med) - P2 | "The R2-GemOx-PD1i regimen demonstrated encouraging antitumor activity with manageable toxicity in R/R DLBCL, providing some reassurance about its safety and tolerability."

Journal • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Endocrine Disorders • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Prospective clinical trial on adjuvant treatment with penpulimab for oral squamous cell carcinoma patients with stage IVa-pN2 after radical resection (ChiCTR) - P=N/A | N=33 | Recruiting | Sponsor: Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Tongji Hospital, Tongji Medical College of Huazhong Universi

New trial • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

3D-Ultrastructural Organization of the Macula Utricle Supporting Cell Cytoplasmic Granules (ARO 2026) - "Previous scanning electron microscopy studies had revealed secretory granules in the cytoplasm of vestibular SCs (Takumida and Anniko, Acta Otol 114:2,150-155,1994)... This study reveals, for the first time, the 3D ultrastructural organization of secretory granules in mouse utricular SCs, and their presence in the human macula utricle. Otopetrin-2 may be among the proteins present in the SCs granules. Insights into SC organization may inform future strategies for hair cell regeneration and cell survival after ototoxic damage or aging."

GFAP

Study on immunotherapy combined with chemotherapy for local oral cancer in OSF (ChiCTR) - P2 | N=51 | Not yet recruiting | Sponsor: Hunan Cancer Hospital; Hunan Cancer Hospital

New P2 trial • Fibrosis • Head and Neck Cancer • Immunology • Oncology • Oral Cancer • Solid Tumor

ALTER-HN005: Anlotinib, Penpulimab and Capecitabine in Recurrent/Metastatic Nasopharyngeal Carcinoma (clinicaltrials.gov) - P2 | N=59 | Active, not recruiting | Sponsor: Sun Yat-sen University | N=110 ➔ 59 | Trial completion date: Oct 2025 ➔ Jul 2026 | Trial primary completion date: Oct 2024 ➔ Jul 2025 | Not yet recruiting ➔ Active, not recruiting

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • Thyroid Gland Carcinoma

Exploration of the mechanism of anlotinib in reversing PD-1 immunotherapy resistance: insights from single-cell sequencing. (PubMed, Cancer Gene Ther) - "The present study aimed to establish a penpulimab-resistant model, delineate anti-PD-1 resistance traits via single-cell RNA sequencing, and unravel the precise mechanisms through which anlotinib-an anti-angiogenic agent-mitigates penpulimab resistance. Identifying Apoe⁺ M2 macrophages, Srgn⁺ M1 macrophages, and Cxcl2⁺ T cells provides key cellular and molecular targets for developing clinically actionable immunotherapies. Taken together, this work validates the preclinical potential of anlotinib combined with immunotherapy for immunotherapy-resistant tumors."

Journal • Oncology • APOE

Anlotinib Plus Penpulimab as Second-line Treatment for Patients With Small Cell Lung Cancer After Failure of Platinum-based Chemotherapy (clinicaltrials.gov) - P2 | N=65 | Completed | Sponsor: Hunan Cancer Hospital | Recruiting ➔ Completed | Trial completion date: Dec 2023 ➔ Apr 2025 | Trial primary completion date: Jun 2023 ➔ Jan 2025

Trial completion • Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A prospective phase 2 study on efficacy and safety of AK105, anlotinib combined with nab-paclitaxel (nab-P) as a first-line therapy in patients(pts) with advanced triple-negative breast cancer (TNBC). (SABCS 2024) - P2 | "The combination of AK105, anlotinib and nab-P showed better treatment response and tolerable toxicity in the treatment of first-line patients with TNBC. Further studies enrolling more patients are still needed."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PD-L2 • PGR

Perioperative penpulimab-based combination therapy in patients with resectable non-small cell lung cancer (ALTER-L043): an open-label, multicenter, randomized, phase II trial. (PubMed, Signal Transduct Target Ther) - P2 | "Across all treatment phases, the incidences of grade ≥3 treatment-related adverse events were 26.7%, 20.0%, and 30.0%, respectively. Penpulimab plus anlotinib with or without neoadjuvant chemotherapy demonstrated promising efficacy and a manageable safety profile in patients with resectable NSCLC, suggesting its potential as a viable perioperative treatment option."

Clinical • Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Final Analysis of AK105-302: A Randomized, Double-blind, Placebo-Controlled, Phase III Trial of Penpulimab Plus Carboplatin and Paclitaxel as First-line Treatment for Advanced Squamous NSCLC (ESMO-IO 2022) - P3 | "Serious TRAEs occurred in 28.3% (P+C) vs. 26.9% (C). TRAEs led to treatment discontinuation were 5.2% in P+C and 3.4% in C. Conclusions These positive data will support penpulimab plus chemotherapy may be a promising and safe first-line treatment for locally advanced or metastatic squamous NSCLC."

Clinical • P3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Primary results from the phase III ALTN-AK105-III-02 study: Anlotinib plus penpulimab versus sorafenib as first-line (1L) therapy for advanced hepatocellular carcinoma (aHCC) (ESMO 2024) - P3 | "The combination of anlotinib + penpulimab significantly prolonged PFS and OS vs sorafenib with no new safety signals observed, and presents as a new 1L treatment option for aHCC."

Clinical • Late-breaking abstract • Metastases • P3 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • AFP • FGFR • KIT

Updated results of anlotinib combined with penpulimab and nab-paclitaxel as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, open-label phase II clinical trial. (ASCO-GI 2026) - P=N/A | "The combination of anlotinib plus penpulimab and nab-paclitaxel as first-line therapy demonstrated promising efficacy and manageable safety profile in patients with advanced ESCC. These findings warrant confirmation in large randomized trials."

Clinical • Metastases • P2 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • FLT1

Efficacy and safety of adjuvant penpulimab in very high-risk clear cell renal cell carcinoma:A prospective, controlled, phase II trial (EAU 2026) - No abstract available

Clinical • P2 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor

Efficacy and safety of immune checkpoint inhibitors for advanced squamous non-small cell lung cancer: a systematic review and network meta-analysis. (PubMed, Front Immunol) - "Compared with chemotherapy, except for ipilimumab+chemo [HR = 0.92,95%CI: (0.59-1.40)], atezolizumab+chemo [HR = 0.88, 95%CI: (0.56-1.40)], and durvalumab+chemo [HR = 0.84, 95% CI: (0.52-1.40)], durvalumab+ tremelimumab+chemo [HR = 0...Cemiplimab [HR = 0.48, 95% CI: (0.34-0.67)] showed the best OS benefit...Sugemalimab+chemo provided the best survival benefit [HR = 0.34, 95% CI: (0.24-0.48)]. For PD-L1≥50% tumors, penpulimab showed excellent OS and PFS; for PD-L1 1-49% tumors, pembrolizumab+chemo and camrelizumab+chemo achieved the best OS and PFS, respectively; for PD-L1≥1% tumors, the tislelizumab+chemo and camrelizumab+chemo showed the best OS and PFS results, while for tumors with PD-L1 <1%, both nivolumab and serplulimab+chemo provided significant survival benefit...Ipilimumab+chemo had the highest incidence of adverse events (AEs) [OR = 2.0, 95% CI:(1.5-2.7)]. https://www.crd.york.ac.uk/prospero/, identifier CRD420251027447."

Checkpoint inhibition • Clinical • IO biomarker • Journal • Retrospective data • Review • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Clinical Studies for the Treatment of Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=194 | Recruiting | Sponsor: Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd. | N=134 ➔ 194

Enrollment change • Solid Tumor

A pathomics model for predicting response to chemo-immunotherapy in lung squamous cell carcinoma: A multicenter study. (PubMed, Lung Cancer) - "We developed a GEP-based pathomics model that provides a practical, cost-effective strategy to identify patients most likely to derive superior survival benefit from first-line CIT over chemotherapy alone."

Clinical • IO biomarker • Journal • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma

Exploration of the mechanism of anlotinib in reversing PD-1 immunotherapy resistance: Insights from single-cell sequencing (ESMO-IO 2025) - "This study explores how anlotinib reverses penpulimab (PD-1 inhibitor) resistance via single-cell sequencing.Methods A penpulimab-resistant model (PD-R) was established by inoculating Lewis lung cancer cells into humanized PD-1 mice with repeated penpulimab dosing. Apoe+ M2, Srgn+ M1 macrophages, and Cxcl2+ T cells are key targets. Findings highlight anti-angiogenic-immunotherapeutic combination potential in resistant tumors."

IO biomarker • Lung Cancer • Oncology • Solid Tumor • APOE • TNFA

An Exploratory Clinical Study for Neoadjuvant Treatment of HER2-low Expressing, Stage II-III Breast Cancer with Vedolizumab in Combination with Pembrolizumab (SABCS 2025) - "Background: HER2-low expressing breast cancer is a heterogenous subtype with limited targeted therapeutic options. Although the clinical benefit may be limited, the combination of Disitamab Vedotin and Penpulimab as neoadjuvant treatment for HER2-low expressing, stage II-III breast cancer shows manageable safety and potential for further refinement, warranting additional investigation to optimize treatment strategies. Pretreatment CD4+ TIL density and total immune infiltration may serve as predictive markers for neoadjuvant response."

Clinical • Combination therapy • IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD4 • CD8 • HER-2 • PD-L1

Penpulimab combined with anlotinib as first-line chemotherapy-free regimen in elderly patients with advanced NSCLC: A phase II single-center study (ESMO Asia 2025) - P=N/A | "This chemotherapy-free combination shows promising efficacy and manageable toxicity in elderly advanced NSCLC, supporting its potential as a tailored strategy for this vulnerable population."

Clinical • IO biomarker • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor