AiRuiKa (camrelizumab)

A range of monoclonal antibodies, including avelumab, atezolizumab, camrelizumab, dostarlimab, durvalumab, sinitilimab, toripalimab, and zimberelimab, have been developed for targeting the interaction between PD-1 and PD-L1. Moreover, the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules. Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.

This project validated that the loss of P2RX1 in neutrophils induces CD8+ T cell dysfunction and affects the GC development, indicating that P2RX1 may be an accurate biomarker for predicting ICI response, thus providing a theoretical basis for the clinical application of ICI.

P2, N=25, Completed, Qilu Hospital of Shandong University | Recruiting --> Completed | Trial completion date: Dec 2024 --> May 2024

P2, N=40, Not yet recruiting, Fudan University

P2, N=10, Recruiting, Fudan University

P2, N=130, Recruiting, Fudan University | Not yet recruiting --> Recruiting | Initiation date: Jul 2024 --> Sep 2024

P1, N=6, Recruiting, West China Hospital | Initiation date: Dec 2024 --> Aug 2024

P2, N=31, Completed, Tianjin Medical University Cancer Institute and Hospital | Trial completion date: Feb 2024 --> Oct 2024 | Trial primary completion date: Feb 2022 --> Mar 2024 | Recruiting --> Completed

P1, N=6, Recruiting, West China Hospital | Initiation date: Oct 2023 --> Dec 2024

The most common grade 3-4 treatment-related adverse events were alanine aminotransferase elevation, aspartate aminotransferase elevation, and lymphopenia. Predefined exploratory analyses indicated that patients with higher peripheral blood CXCR3 + CD8 + T cell abundance, lower immunosuppressive CD4 + T cell abundance, and higher overlap of clonotypes between tumor-infiltrating T cells and circulating T cells, were more likely to respond favorably to the combined therapy.

Camrelizumab plus carboplatin and pemetrexed as first-line therapy continued to demonstrate long-term OS benefit over carboplatin and pemetrexed, with manageable toxicity. Patients who completed 2 years of camrelizumab had enduring response and impressive OS. Current 5-year updated analysis further supports camrelizumab plus carboplatin and pemetrexed as a standard-of-care for previously untreated advanced non-squamous NSCLC without EGFR/ALK alterations.

Compared with chemotherapy alone, Sintilimab or camrelizumab plus chemotherapy seemed to achieve the best progression-free survival (hazard ratio = 0.56, 95% CI 0.46-0.68)...Nivolumab plus ipilimumab resulted in a relatively lower incidence of adverse events of grade ≥3 than other regimens. The combination of immune checkpoint inhibitors (ICIs) with chemotherapy provided a high probability of more effective treatment in comparison with chemotherapy alone for patients with advanced ESCC. Toripalimab and sintilimab plus chemotherapy were ranked as providing the highest OS and PFS benefit in the first-line setting, respectively.

P3, N=214, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting

P=N/A, N=50, Not yet recruiting, Guiping People's Hospital

P=N/A, N=1500, Recruiting, Tianjin Medical University Cancer Institute and Hospital

P2, N=188, Recruiting, The First Affiliated Hospital of Zhengzhou University | Trial completion date: Nov 2026 --> Mar 2027 | Trial primary completion date: Jul 2024 --> Sep 2025

P2, N=49, Not yet recruiting, Fudan University

In the treatment of locally advanced NPC, a randomized phase III study showed equivalence of induction (ICT) and adjuvant therapy (AT; NCT03306121). PD-1 inhibitors have become established in the palliative therapy of NPC in recent years and could now also play an increasing role in curation: the phase III study "Dipper" showed a significantly better 3‑year event-free survival in patients adjuvantly treated with camrelizumab versus placebo after IT and definitive platinum-containing chemoradiotherapy (dRCT; 89% vs. 80%; NCT03427827). The phase III study "Beacon" showed complete remission in 30.5% of patients after IT with gemcitabine/cisplatin and the PD‑1 inhibitor tislelizumab (three cycles), a rate almost twice as high as with gemcitabine/cisplatin alone (NCT05211232). Intensification of dRCT in NPC using EGFR and VEGF inhibitors appears promising (NCT04447326). Abstracts on salivary gland and nasal and sinus cancers emphasize the importance of targeted therapies. In anaplastic thyroid carcinoma, the combination of a PD‑1 inhibitor and a CTLA4 inhibitor showed a 50% response.

P2, N=80, Not yet recruiting, Ruijin Hospital

P2, N=200, Not yet recruiting, Peking University Shenzhen Hospital

Camrelizumab immunotherapy is highly effective in treating aEC. It can increase the one-year survival rate, and elevate the levels of immunoglobulins and immune molecules while reducing the levels of tumor markers and incidence of side effects.

P1, N=6, Recruiting, West China Hospital | Trial primary completion date: Oct 2024 --> Oct 2025

P=N/A, N=14, Recruiting, Fudan University | Not yet recruiting --> Recruiting

Firstly, we describe the patient's treatment history, including failed third-line combination treatments of systemic chemotherapy with bevacizumab or carrelizumab or anlotinib, primary lung tumor recurrence, bilateral lung metastases progression, and new brain metastatic lesion detection. Next, we detail the patient's fourth-line treatment with radiotherapy for brain metastases and two cycles of bevacizumab plus Abraxane and cisplatin, however, the disease progressed and relapsed...However, the patient died due to hypoproteinemia combined with severe pneumonia in December 2023. Furmonertinib may be effective for NSCLC patients with HER2 T8962A and L869R mutations and further studies are needed to confirm these results in prospective clinical trials.

P=N/A, N=75, Not yet recruiting, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine; Shanghai First Maternity and Infant Hospital, Tongji University Sc

P4, N=128, Not yet recruiting, West China Hospital, Sichuan University; West China Hospital, Sichuan University

P2, N=33, Not yet recruiting, Sun Yat-sen University Cancer Center; Sun Yat-sen University Cancer Center

P3, N=885, Completed, Jiangsu HengRui Medicine Co., Ltd. | Active, not recruiting --> Completed

P2, N=39, Completed, Nanfang Hospital, Southern Medical University | Recruiting --> Completed

P3, N=586, Recruiting, Sun Yat-sen University

P2, N=40, Recruiting, Tongji Hospital | Not yet recruiting --> Recruiting

The most frequent grade 3 or 4 treatment-related adverse event was neutropenia (n = 4, 29%). The combination of camrelizumab, gemcitabine, and apatinib showed promising efficacy and acceptable safety in patients with advanced PD-L1-positive biliary tract cancer.

P2, N=58, Terminated, Huazhong University of Science and Technology | Trial completion date: Jun 2023 --> Nov 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Mar 2023 --> Nov 2023; slow recruitment forcing early suspension of screening and enrollment

P3, N=242, Not yet recruiting, Sun Yat-sen University

P2, N=85, Active, not recruiting, Huazhong University of Science and Technology | Recruiting --> Active, not recruiting

BMI is a long-term predictor of the efficacy of lenvatinib plus camrelizumab, and obese/overweight patients have a better prognosis.

P2/3, N=440, Recruiting, Tongji Hospital | Not yet recruiting --> Recruiting

P2, N=40, Recruiting, Tongji Hospital | Not yet recruiting --> Recruiting | Initiation date: Mar 2024 --> Sep 2024

P1, N=6, Recruiting, West China Hospital

Our findings identify CD34 as a novel spatial biomarker for anti-PD-1 therapy efficacy, potentially guiding the selection of aNSCLC patients who are more likely to benefit from ICI treatment. ChiCTR2000040416.

P2, N=3, Terminated, Beijing Sanbo Brain Hospital | N=94 --> 3 | Suspended --> Terminated; Lack of funds

P2, N=21, Recruiting, Beijing Sanbo Brain Hospital | Trial primary completion date: Dec 2023 --> Dec 2024