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Shanghai, China, June 1, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the latest results from over ten studies on lung and gastrointestinal cancer of Henlius’ self-developed innovative anti-PD-1 monoclonal antibody (mAb) HANSIZHUANG (serplulimab, trade name: Hetronifly^® in Europe) were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. HANSIZHUANG is the first anti-PD-1 mAb for the first-line treatment of SCLC and has been approved in over 30 countries and regions including China, Europe and Southeast Asia.

Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. Up to date, HANSIZHUANG has been approved for the treatment of squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), esophageal squamous cell carcinoma (ESCC) and non-squamous non-small cell lung cancer (nsNSCLC). The company has initiated over 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications with more than 4,900 subjects enrolled in China, the U.S., Japan, Turkey, Poland, Georgia and other countries and regions.

Covering first-line treatment of lung cancer, SCLC long-term follow-up confirming survival benefits

As for serplulimab, Henlius covers the full range of first-line treatment of lung cancer. In addition to approved indications for sqNSCLC, ES-SCLC and nsNSCLC, the company is conducting a phase 3 international multi-centre clinical trial of HANSIZHUANG combined with chemotherapy and radiotherapy for limited-stage SCLC (LS-SCLC). At this conference, several research studies in the field of lung cancer were selected for poster presentations. These include the phase 3 clinical trial (ASTRUM-005) of serplulimab as the first line treatment for ES-SCLC led by Professor Ying Cheng from Jilin Cancer Hospital, with the results from the final analysis and 42.4 months of median follow-up data, as well as the first publication of the four-year OS data. Additionally, updated data from a phase 2 study of HLX07 plus serplulimab as first-line treatment for sqNSCLC led by Professor Yi-Long Wu from Guangdong Provincial People’s Hospital was released.

Title: Serplulimab versus placebo plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: efficacy and safety from the end-of-study analysis of the international phase 3 ASTRUM-005 study

Results: Between Sep 12, 2019 and Apr 27, 2021, 585 patients were randomized (serplulimab group, n = 389; placebo group, n = 196) and received either 4.5 mg/kg of serplulimab (serplulimab group) or placebo plus chemo. All 585 patients received at least one dose of study treatment and were included in efficacy and safety analyses. As of data cutoff on May 7, 2024, OS events occurred in 280 (72.0%) patients in the serplulimab arm and 166 (84.7%) in the placebo arm. Consistent with previous reports, marked improvement in OS, PFS, ORR, and DOR were achieved by patients receiving serplulimab plus chemo than those receiving placebo plus chemo. Median OS was 15.8 vs.11.1 months (stratified HR 0.60, 95% CI 0.49–0.73) for respective arms; estimated 4-year OS rate (95% CI) was 21.9% (17.6–26.6) and 7.2% (3.8–12.1). Median PFS according to independent radiology review committee (IRRC) assessment per RECIST v1.1 was 5.8 vs 4.3 months (stratified HR 0.47, 95% CI 0.38–0.57), respectively. Subgroup analysis of OS by age, sex, race, ethnicity, ECOG PS, smoking history, brain metastasis, or PD-L1 expression level revealed similar trends of improvement in the serplulimab arm across subgroups. The safety profile was consistent with previous findings. Serplulimab/placebo-related treatment-emergent adverse events of grade 3 or higher occurred in 136 (35.0%) and 57 (29.1%) patients in respective arms. No new safety signals were identified in this study.

Conclusion: This end-of-study analysis showed that addition of serplulimab to chemo continued to confer survival benefit to previously untreated patients with ES-SCLC along with manageable safety. These results support serplulimab plus chemo for first-line treatment of ES-SCLC.

Title: A phase 2 study of HLX07 plus serplulimab with or without chemotherapy versus serplulimab plus chemotherapy as first-line therapy in advanced or recurrent squamous non-small cell lung cancer

Results: As of 31 December 2024, 27 patients were enrolled and randomly assigned to group A (n=13) and group B (n=14) in part 3. Two groups of patients received HLX07 at 800 mg (group A) or 1000 mg (group B), in combination with serplulimab (300 mg) and chemotherapy. 15 (55.6%) patients had metastatic disease. With a median follow-up of 16.0 months, IRRC-assessed confirmed ORR per RECIST 1.1 was 69.2% (95% CI 38.6–90.9) in group A and 71.4% (95% CI 41.9–91.6) in group B. Disease control rate was 92.3% (95% CI 64.0–99.8), and 100% (95% CI 76.8–100.0), respectively. Median PFS was 15.1 (95% CI 4.1–not available) months in group A and not reached in group B. The median overall survival and duration of response were not reached in either group as of the data cutoff date. All the patients in both groups reported treatment-emergent adverse events (TEAEs).

Conclusion: First-line HLX07 plus serplulimab and chemotherapy showed encouraging preliminary efficacy with a manageable safety profile in patients with advanced sqNSCLC which warrants further investigation.

IIT/Real-world studies validating therapeutic potential for gastrointestinal tumours

In the field of gastrointestinal cancers, the company continues to deepen its clinical exploration of serplulimab. In addition to the approved indication for ESCC, the company is actively advancing a phase 3 clinical trial of HANSIZHUANG plus chemotherapy as neoadjuvant/adjuvant therapy for gastric cancer, as well as the international multi-centre phase 3 clinical trial (ASTRUM-015) of serplulimab in combination with bevacizumab and chemotherapy in first-line treatment of metastatic colorectal cancer (mCRC). Besides, the latest data on 12 IIT/real-world studies of serplulimab in gastrointestinal tumours were also presented at the congress, covering gastric cancer, esophageal cancer, hepatocellular carcinoma, pancreatic cancer, rectal cancer and nasopharyngeal carcinoma.

Title: Safety, efficacy and biomarker analysis from a phase II trial of intensive chemotherapy combined with serplulimab, trastuzumab in patients with advanced HER2-positive gastric cancer

Results: From July 2022 to September 2024, 40 patients with unresectable locally advanced or metastatic HER2-positive gastric cancer were recruited to receive serplulimab, trastuzumab and the DOS regimen. The median follow-up was 7.9 months. There were 10 females and 30 males, with a median age of 59 (31-74). 37 patients were eligible for efficacy assessment. The objective response rate (ORR) was 92% (95% CI: 0.87, 0.96). Median progression free survival has not been reached. 38 patients (95%) experienced adverse events (AEs) of any grade. Grade 3 or above AEs occurred in 14 patients (35%), 2 patients with grade 4 AEs (1 with thrombocytopenia and 1 with myelosuppression). No grade 5 events were observed. The most common AEs were anemia (35%), neutropenia (23%), nausea and vomiting (20%) and leukopenia (20%). 15 (38%) patients had dose interruptions due to AEs, with no treatment discontinuation.

Conclusion: This regimen demonstrated remarkable efficacy with a high ORR and manageable toxicity. Tumor HER2 CNV and ctDNA dynamic monitoring correlated with treatment efficacy. 

Title: Efficacy and safety of second-line therapy with serplulimab, lenvatinib, and paclitaxel in patients with gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) for whom immunochemotherapy failed: A multicenter, single-arm, phase II trial (STILL).

Results: 47 second-line gastric cancer patients for whom immunochemotherapy failed from 8 centers were enrolled to use serplulimab combined with lenvatinib. Patients with CPS ≥1 and ≥5 account to 55.3% (26/47) and 29.8% (14/47). Median follow-up duration was 6.3 months. Among the 41 patients who had underwent at least one assessment, the ORR was 51.2% (21/41, 95% CI: 35.1%-67.1%). The mPFS was 7.1 months (95% CI: 6.1-NA) and the median OS (mOS) was 13.7 months (95% CI: 11.6-NA). The overall incidence of adverse events (AEs) was 72.3%, with 17.0% of patients had grade 3-4 treatment-related AEs. The most common AEs were leukopenia, neutropenia, and numbness.

Conclusion: Continual immunotherapy with serplulimab, combined with lenvatinib and paclitaxel, demonstrated promising efficacy and manageable safety in patients with GC/GEJC. This regimen represents a potential new treatment option for patients who have failed first-line immunochemotherapy.

Title: Continuation of serplulimab-based therapy beyond first progression in advanced gastric/gastroesophageal junction (G/GEJ) cancer: Preliminary results from the SCAFIGC trial

Results: As of November 2024, 53 first-line patients with advanced G/GEJ cancer patients were enrolled, with a median age of 62 years, and 32 patients (60.38%) were aged ≥60 years. Among the 46 patients evaluable for tumor response, the ORR was 52.17% (95% CI: 36.95%-67.11%), with 3 patients achieving complete response (CR), and the disease control rate (DCR) was 82.61% (95% CI: 68.58%-92.18%). The median PFS was 13.73 months (95% CI: 6.43-not reached), with a 12-month PFS rate of 51.57% (95% CI: 36.22%-73.43%), and four patients had PFS of more than one year at the data cut-off date. Median DOR and OS were not yet mature. Patients tolerated treatment well, with grade ≥3 treatment-related adverse events (TRAEs) reported in 5 patients (9.43%), the most common being decreased neutrophil count (3.77%).

Conclusion: Patients with advanced G/GEJ cancer demonstrate promising clinical efficacy and manageable safety after receiving first-line serplulimab combined with chemotherapy.

Title: Efficacy and safety of anti-PD-1 combined with thymosin and SOX in neoadjuvant treatment of cStage III gastric or esophagogastric junctional adenocarcinoma (NAPTSOX24): A prospective, open-label, single-arm, phase II clinical study.

Results: 30 patients with locally advanced gastric cancer were enrolled to receive 3 cycles of serplulimab, thymosin α1 and SOX regimen. Radical gastrectomy plus D2 lymphadenectomy were performed 2–6 weeks post-treatment. Median age of all the 30 cases was 66 years, 90% (27/30) were male, and 46.7% (14/30) had EGJ tumors. Till now, 53.3% (16/30) patients have undergone curative gastrectomy, with 25.0% (4/16) achieving pCR and 37.5% (6/16) demonstrating MPR. Patients with intestinal Lauren type exhibited a significantly better drug response. The variation in CD3+ T cell count was significantly higher in patients with pCR/MPR (P=0.036), suggesting a better predictive value for pathological responses than PD-L1 expression and microsatellite instability status. TRAEs were reported in 66.7% (20/30) cases, with diarrhea (46.7%, 14/30) being the most frequent. No grade 5 TRAEs occurred. Immune-related adverse events were only reported in 10% (3/30) cases.

Conclusion: Combination of anti-PD-1, thymosin α1, and SOX regimen promising efficacy with manageable toxicity in the neoadjuvant setting of locally advanced G/EGJ cancer, independent of PD-L1 expression. Ongoing follow-up will further assess its clinical benefits and safety. (ClinicalTrials.gov identifier: NCT06461910).

Title: Efficacy and safety of serplulimab-based therapy in HER2-negative advanced gastric cancer: A real-world study

Results: 49 patients (49/71, 69.0%) received first-line serplulimab-based therapy, and 22 (22/71, 31.0%) treated in the later lines were included in this analysis. The median age was 65 years (range 35-80) and 71.8% (n=51) were males. The majority received a combination of chemotherapy (n=56, 78.9%), with taxanes+platinum-based (n=30, 42.3%) regimen being the most common, followed by fluorouracil+taxanes-based (n=15, 21.1%), fluorouracil+platinum-based (n=8, 11.3%), and fluorouracil+taxanes+platinum-based (n=3, 4.2%) regimen. The ORR and DCR were 47.2% (95% CI: 33.3-61.4) and 90.6% (95% CI: 79.3-96.9), respectively. As of December 23, 2024, the median follow-up duration was 8.4 months. The median rwPFS of all patients was 10.6 months (95% CI: 7.2-NR), 15.9 months (95% CI: 8.0-NR) for patients who received taxanes+platinum-based regimen, and 23.7 months (95% CI: 23.7-NR) for patients treated with fluorouracil+taxanes-based regimen. Median OS was not reached; the first-line serplulimab treatment showed a superior 1-year OS rate than in later lines (93.8% vs. 49.6%), and patients treated with the fluorouracil+taxanes-based therapy achieved a higher 1-year OS rate than taxanes+platinum-based regimen (100.0% vs. 81.3%). The median DoR was 8.5 months (95% CI: 4.3-NR). A total of 30 patients (42.3%) reported any grade AEs; 12 (16.9%) experienced grade 3-4 AEs, and myelosuppression (n=6, 10.9%) was the most common.

Conclusion: Our real-world study demonstrated that serplulimab-based therapy has a favorable efficacy and acceptable toxicity in HER2-negative advanced gastric cancer patients, and long-term follow-up is needed.

Title: Phase ll trial of anti PD-1 monoclonal antibody and FOLFOXIRI combined with long-course radiotherapy as the total neoadjuvant treatment for proficient mismatch repair, locally advanced, low rectal cancer(PANFORTE)

Results: As of June 2024, 22 patients with pMMR locally advanced low rectal cancer were enrolled to receive FOLFOXIRI plus serplulimab in combination with long-course radiotherapy as the total neoadjuvant treatment, with a median age of 59 years and a median DAV of 4 cm. 86.3% (19/22) patients completed the full TNT regimen. Among the 20 patients eligible for endpoint assessments, the overall CR rate was 75% (15/20), and the sphincter preservation rate was 95% (19/20). 11 (55%) patients achieving cCR opted for a watch-and-wait approach, whereas 9 patients underwent radical surgery. 20% (4/20) achieved pCR and 25% (5/20) had a tumor regression grade (TRG) of 2. The most common severe toxicity was neutropenia (grade 3, 27.3% [6/22]. The scRNA sequencing indicated that non-CR patients exhibited lower T cell infiltration and weaker MHC-I/II signaling.

Conclusion: TNT regimen significantly enhances CR rates and anal preservation in pMMR LALRC compared to historical benchmarks, with an acceptable safety profile. May be an alternative treatment option for LALRC patients who strongly desire anal preservation.

Title: Real-world effectiveness and safety of first-line serplulimab in patients with metastatic or locally advanced esophageal carcinoma

Results: A total of 104 patients were included, with a mean age of 68 years (81 [77.9%] male). Histological subtypes comprised ESCC (80.8%), combined small cell and adenocarcinoma (9.6%), mixed neuroendocrine–non-neuroendocrine neoplasms (5.8%), and neuroendocrine neoplasm (3.8%). Of these, 97 patients (93.3%) received concurrent chemotherapy, 10 (9.6%) underwent targeted therapy, and 21 (20.2%) received radiotherapy. Among 90 evaluable patients, the ORR was 40.0% (95% CI: 29.8–50.9), while the DCR was 97.8% (95% CI: 92.2–99.7). After a median follow-up of 6.8 months (range: 0.6–25.4), the median rwPFS was 12.0 months (95% CI: 8.9–NE), and the median rwOS was not reached (95% CI: 13.3–NE). The estimated 12-month survival rate was 73.5% (95% CI: 60.4–89.3). Overall, 55.8% of patients (n=58) experienced AEs, 18.3% (n=19) reported treatment-related adverse events (TRAEs), and 1.9% (n=2) experienced serious adverse events (SAEs), including hyperkalemia and leukopenia.

Conclusion: This real-world study supports the efficacy of serplulimab as a first-line treatment for metastatic or locally advanced EC, encompassing a wide range of histological subtypes and diverse patient populations. The observed outcomes align with those from randomized controlled trials. The safety profile was consistent with previous findings, with no new safety concerns identified.

Title: Preoperative treatment for potentially resectable esophageal cancer: Insights from a nationwide real-world study

Results: As of December 2023, a total of 95 EC patients who received serplulimab-based neoadjuvant therapy followed by radical surgery were included. The majority were male (n = 86, 90.53%), with a median age of 63 years. SCC accounted for 93 cases (97.89%) of the primary tumors, with most located in the middle thoracic esophagus (n = 68, 71.58%). Patients generally presented with heavy tumor burden, with 88 patients (92.63%) at stage T3/4 and 90 patients (94.74%) with positive lymph nodes. 89 underwent R0 resection, resulting in an R0 rate of 93.68%. The pCR rate was 23.16%, and the MPR rate was 41.05%. Tumor and nodal downstaging rates were 56.84% and 61.05%, respectively. Logistic regression showed that PD-L1-positive patients had significantly higher odds of achieving pCR (OR = 12.73, P = 0.016) and MPR (OR = 2.95, P = 0.031). The overall AE incidence was 96.84%, with 28.42% experiencing grade ≥3 AEs. The most common grade ≥3 AE was pneumonia, which occurred in 22.11% of patients. No new safety signals were identified, and patients generally tolerated the treatment well.

Conclusion: This study represents the large-scale nationwide real-world investigation of serplulimab-based neoadjuvant therapy for esophageal cancer. The findings highlight the potential of serplulimab-based neoadjuvant therapy with manageable toxicity.

Title: A prospective, observational Phase II clinical study evaluating hepatic artery infusion chemotherapy in combination with HLX10 and HLX04 as first-line treatment for patients with advanced hepatocellular carcinoma

Results: As of September 2024, a total of 35 eligible patients were enrolled in the study to receive hepatic artery infusion chemotherapy in combination with HLX10 and HLX04. 28 (80.0%) patients had received at least 3 cycles of treatment. Of the 35 patients, 32 underwent at least one assessment of treatment response, with the best outcomes as follows: 17 (53.1%) achieved partial remission (PR), and 12 (40.0%) had stable disease (SD). The ORR and DCR were 53.1% and 90.6%, respectively. Notably, among patients who had received at least 3 cycles of treatment, 17 patients achieved PR, resulting in an ORR of 63.0%. Moreover, 5 patients underwent successful hepatectomy after at least 3 cycles of treatment, and postoperative pathological evaluation revealed extensive tumor necrosis in the excised tissues. The median follow-up duration was 8.4 months, during which 6 (18.8%) patients experienced disease progression, yielding a one-year PFS rate of 70.5% (95% CI: 47.0%–85.0%). In terms of safety, 17 patients (48.6%) experienced at least one grade 3 or 4 adverse event (AE), with the most frequent being decreased lymphocyte count (20%).

Conclusion: The combination of HLX10, HLX04, and HAIC as first-line treatment for advanced HCC has demonstrated promising efficacy, particularly in patients completing three or more cycles. The safety profile of this combination therapy was acceptable, with manageable AEs. Further investigation in larger trials is warranted.

Title: Phase II trial of serplulimab combined with gemcitabine plus nab-paclitaxel (GnP) and SBRT for metastatic pancreatic cancer as the first-line treatment

Results: As of January 2025, 47 patients with metastatic pancreatic cancer were enrolled to receive to serplulimab and GnP plus SBRT (SGSBRT) as the first-line treatment. 41 patients have been followed for more than 6 months, with all 47 patients achieving efficacy according to the protocol. The 6-month PFS rate was 78.48%. The ORR was 74.47% (35/47), including 1 complete response (CR) and 34 partial responses (PR), and the DCR was 100%, with 12 stable disease (SD). The median PFS was 8.6 months, and the median OS was 15.5 months. The frequent grade 3 drug-related AEs were neutropenia (20/47, 42.55%), leukopenia (19/47, 40.43%), anorexia (18/47, 38.30%), and fatigue (11/47, 23.40%). The correlation between biomarkers and efficacy and prognosis are under-analyzed.

Conclusion: This phase II study has met our preset primary endpoint with 78.48% in 6-month PFS rate, and SGSBRT presented promising efficacy with manageable safety profile and expected antitumor activity. This combination might be a promising option as first-line therapy for Chinese patients with mPDAC.

Title: First-line serplulimab and bevacizumab combined with nab-paclitaxel/gemcitabine followed by mFOLFOX in advanced pancreatic cancer: A phase II trial

Results: 37 patients with advanced pancreatic cancer were enrolled to receive first-line serplulimab and HLX04 (a bevacizumab biosimilar) combined with nab-paclitaxel plus gemcitabine (nab-P/Gem), followed by modified FOLFOX. The average age of the patients was 62 years, and 22 of them (59.5%) were male. Distant organ metastases were present in 34 patients (91.9%), with the liver being the most common site (n=26, 70.3%). The confirmed ORR was 67.6% (95% CI, 49.5-82.6), including 1 patient with a complete response (CR), meeting the primary endpoint. Only 1 patient had progressive disease (PD) as the best response, yielding a DCR of 97.1% (95% CI, 84.7-99.9). the median follow-up was 6.1 months. At the 6.1-month follow-up, the median PFS was 10.5 months (95% CI, 9.7-not reached), with a 6-month PFS rate of 80.0% (95% CI, 65.5-97.7). The median time to response (TTR) was 1.5 months, and the median duration of response (DOR) was 9.3 months. The OS remains immature. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 46.0% of patients. Hematologic toxicities were the most common treatment-emergent adverse events (TEAEs), and no fatal AE were observed.

Conclusion: First-line serplulimab and bevacizumab biosimilar combined with nab-P/Gem-mFOLFOX demonstrates clinical feasibility and promising preliminary outcomes in advanced PC. Further follow-up is required to confirm the survival benefits, and following analyses are needed to explore the mechanisms underlyingthe efficacy of this novel regimen.

Title: Efficacy and safety of serplulimab with DP induction chemotherapy followed by nimotuzumab and IMRT in locally advanced nasopharyngeal carcinoma: A retrospective study

Results: Among the 39 patients meeting eligibility criteria, the median age was 51 years; the median EBV DNA level was 554.0 copies/ml. Via TNM staging, 11(28%) patients were classified as T4 and 12(31%) patients as N3. 19(49%) patients were in stage III, and 20(51%) patients were in stage IVA. As of 31 Dec 2024, the median follow-up was 17 months. Among 38 patients in PPS(table), The CR was 71%, PR was 29%, with ORR and DCR both at 100%(95% CI 91-100). Median OS and PFS were not reached. The 1-year OS rate was 97.4% due to the unexplained death of one patient. Lower CR was noted among patients with T4 disease. Safety profile was consistent with previous reports, furthermore, patients with renal impairment experienced no additional adverse effects.

Conclusion: Serplulimab plus docetaxel and cisplatin induction chemotherapy followed by nimo with IMRT demonstrates promising efficacy and tolerability in treating LANPC.

Advanced solid tumours

Title: A phase 1 study of fixed-dose regimens of serplulimab, an anti-PD-1 antibody, in patients with advanced solid tumors

Conclusion: Fixed-dose regimens of serplulimab showed favorable safety, PK, and PD characteristics and preliminary anti-tumor activity, supporting its further investigation.