Junshi Biosciences presented 26 research results of innovative tumor immune drugs at the 2023 annual meeting of the American Society of Clinical Oncology

Junshi Biosciences announced on June 7, 2023, at the 2023 annual meeting of the American Society of Clinical Oncology (ASCO), Junshi Biosciences carried two innovative tumor immunotherapy (I-O) drugs -- toripalimab (anti-PD-1 monoclonal antibody) and tifcemalimab (anti-BTLA monoclonal antibody), a total of 26 research results were selected. There were 5 oral reports, 15 poster discussions/presentations, and 6 abstract presentations, covering 10 major tumors such as lung cancer, breast cancer, nasopharyngeal cancer, gastrointestinal cancer, urothelial cancer, and melanoma, which received global attention.

It is reported that ASCO annual meeting is one of the largest, highest academic level and most authoritative clinical oncology conferences in the world. Every year, about 40,000 oncology professionals attend the meeting, bringing together experts, professors, doctors and researchers in the field of global oncology to share and discuss the current international cutting-edge clinical oncology research achievements and tumor treatment technology. ASCO annual meeting in 2023 with "the patients with hand in hand, altogether builds on cancer research and treatment of cornerstone" (PartneringWithPatients: TheCornerstoneofCancerCareandResearch) as the theme, Many important research findings and clinical trial results in the field of oncology are released for the first time at the annual meeting. As an emerging force in global innovation, Chinese innovative pharmaceutical companies are increasingly active in the international top academic exchange arena.

TORCHLIGHT study: global first, 35% reduction in risk of disease progression or death

The results of the phase III study (TORCHLIGHT) of Toripalimab combined with nab-P in the treatment of first-diagnosed stage IV or recurrent/metastatic triple-negative breast cancer (TNBC), led by Professor Jiang Zefei of Chinese PLA General Hospital, were presented in the form of Blockbuster research abstract (LBA) in the rapid abstract special session of ASCO Annual Meeting TORCHLIGHT study (NCT04085276) is a randomized, double-blind, placebo-controlled, multicenter phase III clinical study, which enrolled 531 patients with newly diagnosed stage IV or recurrent/metastatic TNBC. It is the first phase III registration study in China to achieve positive results in the field of immunotherapy for advanced TNBC.

As of November 30, 2022 (median follow-up, 14 months), results of the TORCHLIGHT interim analysis showed that:

Compared with chemotherapy alone (nab-P), toripalimab plus nab-P significantly prolonged progression-free survival (PFS) in patients with newly diagnosed stage IV or recurrent metastatic TNBC, with a 35% reduction in the risk of disease progression or death in the PD-L1-positive population. The median PFS by blinded independent central review committee (BICR) was 8.4vs5.6 months, HR=0.65 (95%CI0.47-0.91), two-sided P=0.0102.

A clear trend toward overall survival (OS) benefit with toripalimab plus nab-P was observed in both the PD-L1-positive and intention-to-treat (ITT) populations. The median OS was 32.8vs19.5 months (HR=0.62,95%CI:0.41-0.91) in the PD-L1 positive group and 33.1vs23.5 months (HR=0.69,95%CI:0.51-0.93) in the ITT group, respectively.

Based on the results of TORCHLIGHT study, the National Medical Products Administration (NMPA) has officially accepted the new indication application of toripalimab combined with paclitaxel for injection (albumin bound) for the treatment of PD-L1-positive (CPS≥1) newly diagnosed metastatic or recurrent metastatic TNBC in May this year.

Neotorch study: the first in the world to achieve positive EFS results, with a risk reduction of disease recurrence, progression or death of up to 60%

Professor Shun Lu from Shanghai Chest Hospital, Shanghai Jiaotong University School of Medicine presented more detailed data of Neotorch study in the special session of lung cancer of ASCO Annual meeting. The Neotorch study (NCT04158440) is a randomized, double-blind, placebo-controlled, phase III study involving 404 patients with stage III non-small cell lung cancer (NSCLC). We are the world's first phase III clinical study of anti-PD-1 monoclonal antibody in the treatment of NSCLC in the perioperative period (including neoadjuvant and adjuvant therapy) to announce positive event-free survival (EFS) results.

Neotorch first presented the results of an EFS interim analysis at the April meeting of this year's ASCOPlenary meeting Series and further presented additional EFS subgroup analyses and other data at the current ASCO annual meeting.

As of November 30, 2022 (median follow-up, 18.25 months), results of the interim analysis showed that:

Compared with chemotherapy alone, toripalimab combined with chemotherapy in the perioperative treatment of patients with operable stage III NSCLC followed by toripalimab monotherapy as consolidation therapy significantly prolonged EFS (P< 0.0001), and the risk of disease recurrence, progression or death was reduced by up to 60% (HR=0.40,95%CI:0.277-0.565). OS showed a clear trend toward benefit in the toripalimab-chemotherapy arm.

The EFS benefit with toripalimab-chemotherapy was seen across all key subgroups, regardless of PD-L1 expression status or histologic type (squamous or nonsquamous).

Blinded independent central pathology (BIPR) -assessed major pathological response (MPR) (48.5%vs8.4%,P < 0.0001) and complete pathological response (pCR) (24.8%vs1.0%,P < 0.0001) were significantly better in the toripalimab plus chemotherapy group than in the chemotherapy alone group.

Based on the results of the Neotorch study, a new marketing application for toripalimab combined with perioperative chemotherapy and toripalimab as post-adjuvant consolidation therapy for the treatment of resectable stage III NSCLC was accepted by the NMPA in April this year.

CHOICE-01 study: The final OS data were released, the median OS of non-squamous NSCLC patients was 27.8 months

The CHOICE-01 study, led by Professor Jie Wang from Cancer Hospital, Chinese Academy of Medical Sciences, released the final OS and biomarker analysis data in the special session on Lung cancer of ASCO Annual Meeting. The CHOICING-01 trial (NCT03856411) was a randomized, double-blind, placebo-controlled, multicenter, phase III clinical trial of anti-PD-1 monoclonal antibody combined with chemotherapy as the first-line treatment. A total of 465 newly diagnosed advanced NSCLC patients without EGFR/ALK mutation were enrolled. Studies have repeatedly topped the international academic conference and famous international authoritative periodicals of the journal of clinical oncology (JournalofClinicalOncology, IF = 50.717).

As of August 31, 2022 (median follow-up, 19.4 months), results have shown that:

In the ITT population, toripalimab combined with chemotherapy as first-line treatment for advanced NSCLC without EGFR/ALK mutations significantly prolonged OS compared with chemotherapy alone (median OS 23.8vs17.0 months, respectively), and the risk of death was reduced by 27% (HR=0.73,95%CI:0.57-0.93). Nominal P=0.0108. The 3-year OS was 32.5%vs18.4%, respectively. The improved OS with toripalimab-chemotherapy was observed even with a higher proportion of patients in the placebo-chemotherapy group who crossed over to toripalimab-chemotherapy after disease progression (61.4%).

For non-squamous NSCLC patients, toripalimab combined with chemotherapy was superior to placebo combined with chemotherapy (median OS: 27.8vs15.9 months, respectively), with 11.9 months longer and 51% lower risk of death (HR=0.49,95%CI:0.35-0.69), nominal P< 0.0001.

Further analysis of biomarker results showed that patients with FA-PI3K-Akt signaling pathway gene mutations and IL-7 signaling pathway gene mutations could obtain significantly better PFS and OS benefits from toripalimab-chemotherapy, and patients with SWI/SNF signaling pathway gene mutations had significantly better PFS.

The NMPA has approved toripalimab for the first-line treatment of advanced nonsquamous NSCLC on the basis of the CHOOSE-01 study.

JUPITER-02 study: significantly prolonged the OS of patients with advanced NPC, and the 3-year OS rate was 64.5%

The JUPITER-02 trial, led by Professor Xu Ruihua of Sun Yat-sen University Cancer Center, announced the final OS analysis data at the ASCO annual meeting. The JUPITER-02 trial (NCT03581786) is the first international multicenter, randomized, double-blind, placebo-controlled phase III clinical trial in the field of nasopharyngeal carcinoma immunotherapy. To evaluate the efficacy and safety of toripalimab combined with gemcitabine and cisplatin (GP chemotherapy) as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (r/mNPC), 289 chemotherapy-naive r/mNPC patients were enrolled.

As of November 18, 2022 (median survival follow-up 36.0 months), the results of the final OS and PFS analyses showed that:

Compared with chemotherapy alone, toripalimumab combined with chemotherapy as first-line treatment of r/mNPC significantly prolonged OS (median OS: not reached vs33.7 months, respectively), and the risk of death was reduced by 37% (HR=0.63,95%CI: 0.45-0.89, P=0.0083). The 2-year and 3-year OS rates were 78.0%vs S65.1 % and 64.5%vs49.2%, respectively.

The median PFS in the toripalimab-chemotherapy group was significantly longer than that in the placebo-chemotherapy group. The median PFS in the two groups assessed by the independent review Committee (BIRC) was 21.4 months vs.8.2 months, respectively, which was 13.2 months longer than that in the chemotherapy group. The risk of disease progression or death was reduced by 48% (HR=0.52,95%CI:0.37-0.73), nominal P< 0.0001.

This is the first phase III clinical trial with statistically prespecified (type I error control) data to confirm the survival benefit of immunotherapy plus chemotherapy versus chemotherapy in the first-line treatment of nasopharyngeal carcinoma worldwide, and provides solid evidence for toripalimab plus chemotherapy to become a new standard of care for first-line treatment of nasopharyngeal carcinoma.

Based on the JUPPI-02 results, the NMPA has approved toripalimab for first-line treatment of r/mNPC. The marketing application for this indication is currently under review by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the UK Medicines and Healthcare Products Regulatory Agency (MHRA).

In the perioperative treatment of PD-1 inhibitor for locally advanced gastric cancer, the proportion of patients with TRG0/1 reached 44.4%

The phase II study of perioperative treatment of toripalimab combined with SOX or XELOX chemotherapy versus SOX or XELOX chemotherapy alone for locally advanced gastric or gastroesophageal junction adenocarcinoma led by Professor Xu Ruihua and Professor Zhou Zhiwei from Sun Yat-sen University Cancer Center was the first data at ASCO annual meeting. This study is the first randomized, controlled trial of PD-1 inhibitor combined with chemotherapy in the perioperative treatment of locally advanced gastric cancer in China. The aim of this study is to explore the efficacy and safety of PD-1 inhibitor (toripalimab) combined with SOX or XELOX chemotherapy in the perioperative treatment of locally advanced gastric or gastroesophageal junction adenocarcinoma. A total of 108 patients with resectable cT3-4aN+M0 gastric or gastroesophageal junction adenocarcinoma were enrolled. Studies have shown that compared with chemotherapy alone, toripalimab combined with chemotherapy significantly increased the proportion of patients who achieved pathological complete regression/moderate regression rate (TRG0/1), or brought significant pathological improvement in this population.

The proportion of patients with TRG0/1 in the toripalimab + chemotherapy group was significantly higher than that in the chemotherapy group (44.4%[95%CI:30.9%-58.6%]vs20.4%[95%CI: 10.6%-33.5%]; P=0.009).

Terry split sheet resistance + chemotherapy group observed higher pCR (24.1% [95% CI: 13.5% 37.6%] vs9.3%] [95% CI: 3.1% - 20.3%; P=0.039).

Rates of surgical complications (12% with toripalimab-chemotherapy vs. 13% with chemotherapy) and mortality (1.9% vs. 0%) were comparable between groups, as were treatment-related grade 3-4 adverse events (35% vs. 30%).

Tifcemalimab: Refractory ES-SCLC data are presented for the first time, with a 40% response rate in I-O-naive patients

tifcemalimab, the world's first anti-tumor anti-BTLA monoclonal antibody independently developed by the company, presented the preliminary data of a phase I/II clinical study for extensive stage small cell lung cancer (ES-SCLC) for the first time in the form of a wall poster at the ASCO annual meeting.

This phase I/II, open-label, two-cohort, multicenter study (NCT05000684) was led by Professor Ying Cheng from Jilin Cancer Hospital and Professor Jie Wang from Cancer Hospital, Chinese Academy of Medical Sciences. To evaluate the safety and antitumor activity of tifcemalimab in combination with toripalimab in patients with advanced lung cancer (NSCLC and ES-SCLC).

As of March 14, 2023 (median follow-up 26.4 weeks), the results of the study showed that tifcemalimab combined with toripalimab showed good antitumor activity and was well tolerated in patients with refractory ES-SCLC, especially in I-O treatment-new patients.

Among the 40 evaluable patients, the objective response rate (ORR) was 27.5% (95%CI:5.3-27.9) and the disease control rate (DCR) was 55.0% (95%CI:31.2-62.3).

Among the 20 I-O patients whose efficacy could be evaluated, the ORR of tifcemalimab combined with toripalimab was 40.0% (95%CI:19.1-63.9), and the DCR was 70.0% (95%CI:45.7-88.1). The median duration of response (DoR) was 6.9 months (95%CI: 1.4-6.9), and 3 patients (15.0%) had DoR more than 6 months. The median PFS was 5.5 months (95%CI: 1.4-6.4).

Among the 20 non-I-O treatment-naive patients who could be evaluated for efficacy, 15 patients had I-O treatment history and 5 patients with unknown I-O treatment history, and the best overall response was partial response (PR) in 2 patients (1 case), respectively.

The results of this study support tifcemalimab in combination with toripalimab as a potential treatment option for patients with refractory ES-SCLC. At present, Junshi Biosciences is conducting a combination trial of tifcemalimab and toripalimab in multiple tumor types in China and the United States, and plans to conduct an international multi-center phase III registration clinical study in 2023.