CSCO 2019 Concludes: Key Trends and Product Highlights from Four Days on the Ground

Xiamen, known as Egret Island, is located at the southeastern tip of Fujian Province and serves as a key central city along the southeast coast. In addition to Gulangyu, a renowned tourist destination, the Xiamen International Conference & Exhibition Center hosts numerous domestic and international conferences. Among these, the event that has drawn the most attention from the healthcare industry is the CSCO Annual Meeting, which attracted approximately 30,000 attendees to Xiamen in 2019.

CSCO was initially established by a group of young physicians who recognized the growing international trend toward multicenter clinical research. Its original name was the “Clinical Collaboration Professional Committee.” This positioning was clearly defined: to enable Chinese oncology scholars to conduct multicenter trials through clinical collaboration. In retrospect, the initial concept was highly forward-looking. Over the past 22 years, the organization has evolved from the “Clinical Collaboration Professional Committee” into CSCO. During this same period, CSCO has witnessed the profound transformations in China’s clinical diagnosis and treatment, marking a shift from evidence-based and experience-based medicine toward precision medicine.

From September 18 to 22, 2019, VCBeat also dispatched a team of reporters to Xiamen to attend this annual conference on oncology research. After several days of visiting the exhibition and attending satellite meetings and press conferences, we have summarized the five major trends of the 2019 CSCO Annual Conference as follows:

1. Immunotherapies Continue to Gain Momentum

2. The Rise of Companion Diagnostics

3. Competition for Lung Cancer Targeted Therapies Intensifies Again

4. Targeted Therapies for Rare Tumors Are Gaining Momentum

5. AI and Smart Healthcare Enter Clinical Oncology

Even before entering the exhibition hall, we could sense the intense rivalry in the PD-1 market. From Hall B3 to the conference center, advertising spaces along the route were almost entirely dominated by a few key players. Wherever Opdivo (“O” drug) was present, Keytruda (“K” drug) was sure to follow; wherever Tyvyt appeared, Tuoyi was close behind. Bristol Myers Squibb (BMS) even set up a dedicated sub-booth exclusively for Opdivo.

Furthermore, Hengrui and BeiGene have shown no signs of backing down. In addition to placing posters for its product AiRuiKa (camrelizumab) along the main thoroughfare at the entrance of the convention center, Hengrui has also emphasized its PD-1 inhibitor through its exhibition materials and satellite symposium (Hengrui Immunology Symposium). Although BeiGene is currently somewhat behind, it remains highly confident, as its investigational anti-PD-1 antibody tislelizumab and investigational BTK inhibitor zanubrutinib are both on the verge of market approval.

Next, we will focus on PD-1 antibodies and review the activities of these six companies at the 2019 CSCO Annual Meeting.

On June 15, 2018, the NMPA approved BMS’s PD-1 inhibitor Opdivo (brand name: Opdivo) for marketing in China, indicated for second-line treatment of non-small cell lung cancer (NSCLC). Beyond this, BMS has also been actively seeking breakthroughs in first-line therapies.

It is understood that the CA209-9LA trial conducted by BMS in China is a Phase III, randomized study comparing nivolumab and ipilimumab combined with chemotherapy versus chemotherapy alone as first-line treatment for stage IV non-small cell lung cancer (NSCLC). The study stratified patients based on three criteria: PD-L1 expression, sex, and histology, assigning them to either the “nivolumab + ipilimumab + histology-based platinum-doublet chemotherapy” group or the “histology-based platinum-doublet chemotherapy” group. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and ORR/PFS/OS in subgroups with different PD-L1 expression levels and tumor mutational burden (TMB).

At the “IO MDT” satellite symposium held on the 19th, the main discussions also centered on immunotherapy for non-small cell lung cancer (NSCLC). In addition to continuing to focus on NSCLC through combination therapies, multiple studies of Opdivo in gastrointestinal and urologic tumors (including adjuvant therapy) have reached certain milestones.

For Merck & Co., immunotherapy for lung cancer is their current strength.

On July 25, 2018, the National Medical Products Administration (NMPA) approved MSD’s PD-1 inhibitor Keytruda for marketing in China, indicated for locally advanced or metastatic melanoma that has progressed following first-line therapy. In March 2019, Merck & Co. announced that the NMPA had formally approved Keytruda in combination with pemetrexed and platinum-based chemotherapy as a first-line treatment for metastatic non-squamous non-small cell lung cancer (NSCLC) that is negative for epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK).

Keytruda is the first PD-1 inhibitor approved by regulatory authorities to expand its indications across a broader range of cancer types. Merck & Co. proudly featured the slogan “First-Line NSCLC: Hope for Survival” on its poster. At this CSCO satellite symposium, Merck’s message was equally resounding, with the straightforward and bold theme “2019 Merck Lung Cancer Immunotherapy Satellite Symposium.” During the meeting, Merck invited clinical experts including Wang Lifeng from Nanjing Drum Tower Hospital, Wang Hanping from Peking Union Medical College Hospital, and Dong Yuchao from Changhai Hospital Affiliated to Naval Medical University. They shared insights on topics such as “Redefining Survival Hope for First-Line Non-Squamous NSCLC Patients Through Immunotherapy Combined with Chemotherapy,” “Practical Management of Adverse Events Associated with Pembrolizumab in NSCLC Treatment,” and “Efficacy of Pembrolizumab in NSCLC Patients with Low or Negative PD-L1 Expression.”

Furthermore, in June, Merck & Co. announced five-year efficacy and safety data for Keytruda monotherapy in advanced non-small cell lung cancer (NSCLC). In this study, the 5-year overall survival (OS) rate was 23.2% among treatment-naïve patients (n=101) receiving pembrolizumab as first-line therapy, and 15.5% among previously treated patients (n=449) receiving pembrolizumab as later-line therapy. Notably, among patients with tumor cell PD-L1 expression TPS (Tumor Proportion Score) ≥50%, the 5-year OS rate was 29.6% in treatment-naïve patients (n=27) and 25.0% in previously treated patients (n=138).

Recently, the company announced updated pooled subgroup analysis data from first-line Keytruda treatment. The results showed that in patients with advanced non-squamous and squamous non-small cell lung cancer (NSCLC) whose tumors did not express PD-L1 (Tumor Proportion Score [TPS] <1%), Keytruda combined with chemotherapy improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

The market footprint of PD-1 inhibitors has expanded from rare cancers to more prevalent ones. For Merck & Co., lung cancer represents a key battleground in its competition with Bristol Myers Squibb (BMS). Given the larger patient population with lung cancer, Merck’s current strategy may be to capitalize on its momentum and widen its lead over BMS in this therapeutic area.

On December 17, 2018, the National Medical Products Administration (NMPA) approved the first domestically produced PD-1 monoclonal antibody, toripalimab injection (brand name: Tuoyi), developed by Shanghai Junshi Biosciences Co., Ltd., for the treatment of patients with unresectable or metastatic melanoma who had failed prior systemic therapy. As the first domestically produced PD-1 monoclonal antibody to receive marketing approval, Junshi Biosciences ushered in a new chapter in cancer immunotherapy in China.

At this year’s CSCO Annual Conference, Junshi Biosciences held two satellite symposia, focusing primarily on immunotherapy for non-small cell lung cancer (NSCLC) and gastrointestinal tumors. Junshi Biosciences announced the sharing of Phase II study data for Tuoyi (toripalimab) in two indications—bladder urothelial carcinoma and NSCLC—achieving remarkable interim results. Junshi Biosciences is one of the few innovative pharmaceutical companies in China that currently holds both popular antibody drugs and targeted therapies. In previous interviews, we learned that following the launch of its PD-1 product, Junshi Biosciences’ development strategy has centered on further extending and expanding around this product, with combination therapies constituting a significant proportion of these efforts.

Non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancer cases, with a high proportion of patients harboring EGFR mutations. First-line treatment for these patients typically involves EGFR tyrosine kinase inhibitors (EGFR-TKIs); however, subsequent therapeutic options are extremely limited upon treatment failure. To address this challenge and optimize treatment strategies, Professor Zhou Caicun from Shanghai Pulmonary Hospital affiliated with Tongji University spearheaded the first clinical study in China targeting EGFR mutation-positive NSCLC. This study evaluated the combination of toripalimab with the chemotherapy agents pemetrexed and carboplatin. The results of this Phase II clinical trial were presented as an oral report at the recently concluded World Conference on Lung Cancer (WCLC), marking the debut of toripalimab in the field of lung cancer. According to Professor Zhou, the lead investigator, the synergistic effect of immunotherapy combined with chemotherapy significantly enhances efficacy compared to historical data for chemotherapy alone, which showed an objective response rate (ORR) of approximately 30% and a progression-free survival (PFS) of around 4 months. This approach offers new therapeutic insights for patients with EGFR-mutated NSCLC.

As of now, Junshi Biosciences’ R&D pipeline comprises 19 products, including 13 innovative biologics, three small-molecule drugs, and one biosimilar. In addition to in-licensing and acquisition, the company has collaborated with more than ten domestic pharmaceutical companies on combination therapy initiatives involving multiple first-in-class novel drugs. Among the 14 pivotal registration clinical trials currently underway at Junshi, the vast majority are evaluating combination therapies. These combinations are primarily based on pairing its PD-1 inhibitor with established anticancer agents or treatment modalities, such as targeted therapies and chemotherapy.

Currently, several investigational products for lung cancer, breast cancer, gastrointestinal tumors, and nasopharyngeal carcinoma are in Phase III clinical trials. The company aims to secure approval for new PD-1 indications annually over the next three to four years.

On December 24, 2018, the National Medical Products Administration (NMPA) approved the market launch of Innovent Biologics’ PD-1 antibody drug, sintilimab injection (brand name: Tyvyt), for the treatment of relapsed or refractory classical Hodgkin’s lymphoma in patients who have undergone at least two lines of systemic chemotherapy. In addition to the approved indications, Innovent’s research and development pipeline includes ongoing investigations into the use of its PD-1 monoclonal antibody for indications such as lung cancer, esophageal cancer, gastric cancer, and Hodgkin’s lymphoma.

At this year’s CSCO Annual Meeting, Innovent Biologics presented the results of two clinical trials through both a symposium session and an oral presentation.

On September 19, 2019, Innovent Biologics presented, in the form of an oral report, the results of a randomized, double-blind Phase 3 study (CTR20160848) evaluating the efficacy and safety of IBI305 (a bevacizumab biosimilar) and bevacizumab in combination with paclitaxel/carboplatin as first-line treatment for patients with advanced non-squamous non-small cell lung cancer.

A total of 450 patients were enrolled in the CTR20160848 study, including 224 in the IBI305 group and 226 in the reference drug bevacizumab (RBv) group. As of March 31, 2019, in the Full Analysis Set (FAS), the updated objective response rates (ORR) assessed by central imaging review were 47.1% and 46.8%, respectively. The ORR ratio was 1.01 (90% CI: 0.846, 1.181), falling within the equivalence margins (0.75, 1.33) specified in the study protocol. As of May 22, 2019, results showed that the median progression-free survival (PFS) assessed by investigators was 7.3 months for the IBI305 group and 7.5 months for the RBv group, with no statistically significant difference (p=0.893).

The following day, Innovent also announced data from two studies on IBI301 (a rituximab biosimilar) co-developed with Eli Lilly and Company: a multicenter, randomized, double-blind, parallel-controlled clinical study comparing the pharmacokinetics and safety of IBI301 versus rituximab injection in subjects with CD20-positive B-cell lymphoma (CTR20160770); and a multicenter, randomized, double-blind, parallel-controlled, Phase III clinical study comparing the efficacy and safety of IBI301 combined with CHOP (I-CHOP) versus the originator rituximab injection combined with CHOP (R-CHOP) in previously untreated patients with diffuse large B-cell lymphoma (DLBCL) (CTR20160493).

Innovent Biologics and Eli Lilly and Company jointly conducted a pharmacokinetic (PK) comparative study of IBI301 versus the originator rituximab injection in patients with CD20-positive B-cell lymphoma who had achieved complete response after prior treatment, as well as a clinical efficacy comparative study in previously untreated patients with CD20-positive diffuse large B-cell lymphoma (DLBCL), to evaluate the clinical similarity between IBI301 and the originator rituximab injection. Clinical trial results demonstrated that both primary comparative studies met their primary endpoints.

A pharmacokinetic (PK) comparative study of IBI301 versus the originator rituximab injection was conducted in 181 patients with CD20-positive B-cell lymphoma who achieved complete response (CR) after treatment, including 89 patients in the IBI301 group and 92 in the originator group. The primary PK endpoint (AUC0–inf) demonstrated equivalence between the IBI301 and originator groups, with the geometric mean ratio and its 90% confidence interval both falling within the predefined equivalence range of 80.00% to 125.00%.

In the Phase III efficacy comparison study of IBI301 combined with the CHOP regimen versus the originator drug combined with the CHOP regimen in previously untreated diffuse large B-cell lymphoma (DLBCL), a total of 420 subjects were enrolled, with 210 subjects in each group. The data cutoff date was January 18, 2019. In the full analysis set, the objective response rates (ORR) assessed by central imaging review for the IBI301 group and the originator drug group were 89.9% and 93.8%, respectively. The study met its primary endpoint, demonstrating that IBI301 is clinically equivalent to the originator drug rituximab in terms of efficacy and has a similar safety profile in patients with previously untreated DLBCL. Based on these clinical data, the National Medical Products Administration (NMPA) accepted the New Drug Application (NDA) for IBI301 on June 26, 2019, and granted it priority review.

Regrettably, Innovent Biologics did not disclose new data on its PD-1 product this time. However, the company has recently announced patient recruitment for several clinical trials related to liver cancer. It appears that liver cancer will become another major target market for Innovent, following lymphoma and lung cancer.

Hengrui’s PD-1 monoclonal antibody was approved for market launch in late May 2019, indicated for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma who have received at least two prior lines of systemic chemotherapy. Among the five PD-1 monoclonal antibodies already marketed in China, Hengrui was relatively late to obtain regulatory approval.

Hengrui has five innovative drugs on the market, one product under review for marketing approval, six products in Phase III clinical trials, and nearly 30 candidates in Phase I and II clinical trials. Despite having blockbuster products such as apatinib, which generates over RMB 1 billion in annual sales, Hengrui has placed greater strategic emphasis on camrelizumab following its launch. The company dedicated a satellite symposium exclusively to camrelizumab. In addition to hematologic malignancies, gastrointestinal cancers, and lung cancers—areas also pursued by other companies—Hengrui has conducted research on the use of camrelizumab for the treatment of advanced hepatocellular carcinoma.

It is well known that China bears a heavy burden of liver disease; however, patients with liver cancer do not have access to the same range of treatment options as those in developed countries. Regarding imported products, indications for use are predominantly studied based on the epidemiological characteristics of Western populations. For liver cancer, a malignancy with distinct features in China, greater hope may rest on domestically produced drugs.

Camrelizumab has sequentially conducted over 50 clinical trials targeting 12 indications, including Hodgkin lymphoma. These indications encompass common malignancies such as gastric cancer, liver cancer, non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma, and esophageal cancer. Furthermore, Phase III clinical trials have been initiated for several cancer types, including liver cancer, NSCLC, and esophageal cancer. At the 2018 ESMO Congress, Professor Qin Shukui from the General Hospital of the Eastern Theater Command of the PLA presented the “Preliminary Report of a National Multicenter Phase II Clinical Trial of Camrelizumab as Second-Line Treatment for Chinese Patients with Advanced Hepatocellular Carcinoma.” The report disclosed that camrelizumab, a humanized anti-PD-1 IgG4 monoclonal antibody, can efficiently block the binding of hPD-1 to hPD-L1, effectively stimulate PBMC expansion and interferon release, and has demonstrated superior antitumor efficacy in mouse model studies.

Preliminary results indicate that, as of May 16, 2018, camrelizumab demonstrated high efficacy and safety as a second-line or subsequent therapy in patients with advanced hepatocellular carcinoma who had failed or were intolerant to prior sorafenib or oxaliplatin-based regimens. Even among subjects with poor baseline status, camrelizumab still yielded favorable outcomes in terms of objective response and survival benefit.

On May 16, 2019, Hengrui Medicine submitted a new marketing application for an additional indication of camrelizumab (CXSS1900023). Although the specific indication remains undisclosed, if it were hepatocellular carcinoma, it would likely better align with market expectations.

At this year’s CSCO Annual Meeting, several senior executives from BeiGene—including Dr. Wu Xiaobin, President; Ms. Liu Yan, Vice President; and Ms. Qian Hongyu, Vice President—were all in attendance. Judging by their demeanor, they were not at all affected by the previous “malicious short-selling” incident. Dr. Wu even joked, “They always target the most outstanding companies across various sectors in China. Looking at it that way, there’s a bit of bittersweet humor in it.”

Returning to the main topic, although BeiGene’s tislelizumab is still in the approval stage, its strength should not be underestimated given its regulatory filing progress and operational layout.

BeiGene has submitted two indications: relapsed/refractory classical Hodgkin lymphoma and previously treated or metastatic urothelial carcinoma, with the former having received IND acceptance. Additionally, the company has seven first-line therapies in Phase III clinical trials, targeting non-squamous non-small cell lung cancer, squamous non-small cell lung cancer, extensive-stage small cell lung cancer, urothelial carcinoma, hepatocellular carcinoma (global), gastric cancer (global), and esophageal squamous cell carcinoma (global). Concurrently in clinical development are second-line esophageal squamous cell carcinoma (global), Stage III non-small cell lung cancer (global), nasopharyngeal carcinoma, and esophageal squamous cell carcinoma, among other indications.

Meanwhile, BeiGene’s BTK small-molecule inhibitor, zanubrutinib, has had its applications accepted by both the NMPA and the FDA, and has been granted Priority Review status in the United States. This makes it one of the few innovative drugs from China to successfully expand beyond domestic borders. With the support of these two blockbuster products, BeiGene is advancing on dual fronts. In terms of R&D, BeiGene has consistently emphasized its internationalization strategy, with the majority of its core staff hailing from multinational pharmaceutical companies. If the company seeks simultaneous market entry for its anti-PD-1 monoclonal antibody both domestically and abroad, the experience gained with zanubrutinib could provide a significant advantage in its global expansion.

Additionally, CStone Pharmaceuticals presented for the first time study data on its investigational anti-PD-L1 antibody CS1001 from the esophageal squamous cell carcinoma (ESCC) cohort of the Phase Ib GEMSTONE-101 trial.

The trial announced herein is a Phase Ia/Ib, open-label, multiple-dose dose-escalation and expansion study conducted in China among patients with advanced solid tumors or lymphoma, designed to evaluate the safety, tolerability, pharmacokinetic profile, and antitumor efficacy of CS1001. The currently reported cohort study in esophageal squamous cell carcinoma (ESCC) primarily aims to preliminarily assess the antitumor efficacy of CS1001 combined with cisplatin and fluorouracil (CF) chemotherapy as first-line treatment in this patient population, and to further evaluate the safety and tolerability of CS1001 when used in combination with this chemotherapy regimen.

Professor Li Jin, Director of the Department of Oncology at Shanghai East Hospital affiliated with Tongji University, Chairman of the Chinese Society of Clinical Oncology (CSCO), and presenter of this study, stated, “The data from this trial demonstrate that CS1001 combined with CF chemotherapy as a first-line treatment exhibits robust antitumor activity in patients with advanced esophageal squamous cell carcinoma, achieving an objective response rate of 77.8% with durable responses. Furthermore, the overall safety and tolerability profile was favorable.”

If last year the PD-1 monoclonal antibody market was characterized by undercurrents of tension, this year it is fraught with intense competition. The focus has shifted from racing to be the first to market to competing on sales volume and approved indications. Within just one year, China’s immuno-oncology therapy market has heated up rapidly, mirroring the rivalry between BMS and Merck & Co. in overseas markets—a scenario that may now be unfolding domestically.

The escalating competition in the field of immunotherapy drugs has naturally driven companion diagnostic companies to strengthen their presence in immunoassay diagnostics. However, this trend was already evident last year, so perhaps we can explore other topics this year.

Let us examine what the companies that have already obtained approval are doing.

Turning to Novogene, in addition to continuing to focus on its current core product for lung cancer, the company’s satellite symposium also addressed topics related to real-world studies. These included a presentation by Wang Xiaojing from the First Affiliated Hospital of Bengbu Medical College on “Real-World Study: The Relationship Between Driver Gene Mutations and PD-L1 Expression in the Chinese Population,” and a thematic report by Ma Jie from Henan Cancer Hospital on “Interpretation of In-Hospital Real-World NGS Testing Data.”

In contrast, the topics presented by Genetron Health at this event were distinct from the aforementioned two. Professor Fang Wenfeng reported the results of China’s first large-scale study exploring biomarkers for immunotherapy during the satellite symposium. Furthermore, large-panel tumor testing became the focal point of the session. Researcher Huang Jie shared the latest research advances and future development trends in next-generation sequencing (NGS) large-panel testing, as well as the standardization and evaluation of NGS-based large panels for detecting tumor gene mutations.

In fact, the themes of the satellite symposia hosted by these three companies were frequently mentioned at this year’s CSCO conference; Illumina’s satellite symposium focused on large-panel testing.

In 2017, the FDA approved the first NGS-based large-panel tumor testing platform (MSK), marking the beginning of widespread attention to large-panel tumor testing in the Chinese market. Prior to testing, large-panel assays do not require predefined target regions, enabling the detection of unknown genomic alterations. This approach allows for comprehensive profiling of all variants in a single test and helps address missed mutations inherent in current diagnostic methods.

Real-World Study (RWS)Since the formal introduction of the concept of evidence-based medicine in 1992, more than two decades have passed, during which time it has profoundly influenced clinical medical practice and medical research. Real-world studies originated from pragmatic clinical trials and were initially applied in the field of pharmacoepidemiology. The term “real world” refers to settings with larger sample sizes that cover a broader and more representative population. The value of such studies lies in addressing questions that randomized controlled trials cannot answer, such as population differences in the actual application of diagnostic and therapeutic products and clinical adherence. In real-world medical practice, treatment measures are selected non-randomly based on patients’ actual conditions and preferences. Long-term evaluations are conducted with an emphasis on meaningful clinical outcomes, thereby assessing the external validity and safety of interventions across broad, real-world healthcare settings.

Professor Lu Shun from Shanghai Chest Hospital has conducted research integrating real-world data with large-panel testing to guide targeted and immunotherapy for lung cancer. Based on a comparison of sequencing depth and breadth, current data demonstrate favorable performance of large-panel testing. At a satellite symposium hosted by Genetron Health, Dr. Niu Xiaomin from Professor Lu Shun’s team noted that as tumor mutation burden (TMB), an important biomarker for immunotherapy, has been incorporated into the NCCN Guidelines for Non-Small Cell Lung Cancer (NSCLC), large-panel testing will become increasingly critical in tumor diagnosis.

In fact, both real-world studies and large-panel tumor testing ultimately aim to further reconstruct the true nature of diseases and clinical diagnosis and treatment. Real-world studies serve to clinically validate technologies, more accurately reflecting their value in clinical practice. Large-panel testing involves an in-depth exploration of the genetic essence of diseases, using such platforms to unravel the complexities of cancer as a multifaceted disease. Underlying both trends is a shared commitment to the deep exploration of oncology.

Prior to this year’s CSCO opening, some media outlets extracted keywords from satellite symposium topics to predict the annual most prevalent cancer types. Lung cancer unsurprisingly emerged as the most closely watched malignancy, with its level of interest more than double that of breast cancer, which ranked second. Although immunotherapy, riding high on popularity, has swept through the field in an iterative manner, targeted therapies—long constrained by drug resistance—remain a seasoned and resilient force with significant untapped potential. After all, clinicians have accumulated extensive practical experience; therefore, using targeted drugs alone or in combination is evidently easier to initiate and manage when treating unfamiliar patients.

Over the past four days, the most prominent event in the field of targeted therapies for lung cancer has been the approval of AstraZeneca’s third-generation EGFR-TKI, osimertinib (brand name: Tagrisso), in China as a first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR mutations. With this approval, first-, second-, and third-generation TKIs are all available in China for first-line treatment of EGFR mutation-positive NSCLC, sparking considerable attention and discussion.

In-depth exploration of the mechanisms underlying resistance to EGFR-TKIs has long been a research hotspot. In terms of chemical structure, first-generation TKIs feature a quinazoline core ring; second-generation EGFR-TKIs are based on the quinazoline core but incorporate an acrylamide side chain modification; third-generation TKIs utilize a pyrimidine ring as the core, with an unsaturated acryloyl group attached to the side chain that forms a covalent bond with C797, resulting in irreversible binding. Additionally, the removal of the aromatic head group addresses the steric hindrance caused by the T790M mutation. Owing to these structural improvements, the third-generation TKI osimertinib demonstrates superior selectivity in effectively inhibiting both the T790M mutation and EGFR sensitizing mutations.

However, in clinical practice, physicians typically prioritize first-generation drugs as the initial choice due to their reasonable cost, well-established efficacy, and mild adverse reactions. For patients with rare mutations, second-generation drugs are recommended, although they are associated with more significant adverse effects. Third-generation drugs are considered a lower-priority option; while current studies indicate that third-generation EGFR-TKIs can prolong progression-free survival (PFS) and show a trend toward improved overall survival (OS), they are not yet covered by national medical insurance and remain expensive. Given the need for subsequent-line therapy after resistance to first-generation agents develops, a combination regimen of first- and third-generation drugs is generally recommended.

Osimertinib’s entry into first-line therapy was immediately met with a head-on challenge from Pfizer. At the satellite symposium held on September 20, themed “A Decade of Swordsmanship, Triumphant Return,” Pfizer explicitly outlined four counteroffensive advantages of its second-generation EGFR-TKI, dacomitinib, and presented supporting clinical data.

1. Dacomitinib is the first EGFR-TKI to demonstrate a clinically meaningful improvement in overall survival (OS);

2. Dacomitinib as first-line therapy demonstrated a longer median PFS compared to first-/second-generation TKIs;

3. Dacomitinib showed no inferiority in median PFS compared to osimertinib;

4. In non-head-to-head subgroup analyses, dacomitinib may demonstrate superior PFS outcomes compared to third-generation TKIs in the Asian population.

From this perspective, osimertinib’s adoption as a first-line therapy has ignited fierce competition rather than secured an unassailable market lead. However, where there is direct confrontation, there are also flanking maneuvers. AstraZeneca’s challenger in this regard is Beta Pharma, the manufacturer of icotinib (brand name: Conmana), a first-generation EGFR-TKI inhibitor.

Once the pride of Sinopharm, Beta Pharma’s flagship product, Conmana (icotinib), is China’s first independently developed EGFR-TKI drug and the third such medication to be launched globally. As its patent expiration date approaches and competing drugs with the same target and indications continue to be iterated, Conmana’s sales are under unprecedented pressure. For Beta Pharma, external skepticism regarding its overly narrow product pipeline has been incessant. In April this year, VCBeat learned during an invited visit to Beta Pharma that the company had made significant progress in the independent development of a novel drug targeting a different mechanism.

After five months, this development has finally been unveiled. The new drug Beimeina (ensartinib) is a next-generation ALK inhibitor with inhibitory potency ten times that of Pfizer’s second-generation ALK inhibitor crizotinib, and it demonstrates significant clinical efficacy in patients who have developed resistance to the latter. Case data presented by Beta Pharma at this year’s CSCO conference confirmed that among patients previously treated only with crizotinib, the objective response rate was 69%, the median progression-free survival was 9.0 months, and the drug achieved central nervous system responses, with an intracranial response rate of 64%.

It is understood that the ALK gene is a potent oncogene, with its primary driving mechanisms being gene fusions, gene amplification, and point mutations. The fusion of ALK genes leads to the activation of tyrosine kinase, which in turn activates multiple downstream pathways such as JAK/STAT, PI3K/mTOR, and MAPK, resulting in uncontrolled cell proliferation and apoptosis. In non-small cell lung cancer (NSCLC), resistance mechanisms to first- and second-generation ALK-TKIs differ; there are more ALK resistance mutations associated with second-generation drugs, and the specific resistance mutations vary among different second-generation ALK-TKIs.

Professor Wu Yilong, Deputy President of Guangdong Provincial People’s Hospital and a leading authority on lung cancer, pointed out that in recent years, targeted therapy against driver genes has fundamentally transformed the treatment paradigm for patients with advanced-stage cancer. With advances in molecular biology and next-generation sequencing (NGS) technologies, an increasing number of rare driver gene targets have been identified, such as ROS1, BRAF, MET, and RET. Although these rare driver genes occur at low frequencies in tumors—for instance, RET fusions are present in approximately 1–2% of non-small cell lung cancer (NSCLC) cases—drug development targeting these rare driver gene remains critically important given the large global population of cancer patients.

Hutchison China MediTech held a satellite symposium to present the therapeutic advances of surufatinib in neuroendocrine tumors. Surufatinib targets VEGFR, and its first approved indication is for non-pancreatic neuroendocrine tumors (NETs). No drug targeting this specific mechanism has been approved globally for this indication.

Surufatinib is a novel oral anti-angiogenic and immunomodulatory kinase inhibitor that inhibits angiogenesis by blocking vascular endothelial growth factor receptors (VEGFR1, 2, and 3) and fibroblast growth factor receptor 1 (FGFR1). Meanwhile, surufatinib also inhibits colony-stimulating factor-1 receptor (CSF-1R). By inhibiting these kinases, surufatinib not only effectively suppresses tumor angiogenesis but also enhances anti-tumor activity by modulating tumor-associated macrophages. Therefore, surufatinib is a new anti-cancer agent with dual mechanisms of action: anti-angiogenic and immunomodulatory effects.

Surufatinib chose to enter the market by first targeting neuroendocrine tumors.

Based on its mechanism of action, surufatinib exerts a dual effect by simultaneously inhibiting tumor angiogenesis and modulating the immune system, making it potentially more suitable for combination with other immunotherapies. Surufatinib is currently undergoing multiple proof-of-concept studies in the United States and China, with several late-stage clinical trials being conducted in China. This drug is poised to play a significant role in the treatment of various solid tumors.

Novartis is exploring the combination of trametinib, acquired through an asset swap with GSK, and dabrafenib for the treatment of melanoma. Trametinib and dabrafenib target MEK and BRAF, respectively; both were approved in 2013 for the indication of melanoma.

According to reports, although monotherapy with BRAF inhibitors has a rapid onset of action and high response rates, the duration of efficacy is relatively short, with patients quickly developing acquired resistance and tumor recurrence. Meanwhile, BRAF inhibitor monotherapy may induce secondary malignancies such as cutaneous squamous cell carcinoma (SCC), and compensatory activation of MAPK bypass pathways can also lead to various adverse reactions.

Preclinical studies have demonstrated that adding a MEK inhibitor to BRAF inhibitor therapy can prevent and delay the reactivation of the MAPK pathway, while simultaneously suppressing the occurrence of cutaneous squamous cell carcinoma (cSCC) and various adverse reactions. To date, multiple studies have confirmed the efficacy and safety of combining BRAF and MEK inhibitors in the treatment of BRAF-mutant melanoma. Both the COMBI-V and COMBI-D trials showed that dabrafenib plus trametinib (D+T), compared with vemurafenib monotherapy or dabrafenib monotherapy, significantly prolonged median overall survival (mOS) and median progression-free survival (mPFS), and improved the objective response rate (ORR). The combination regimen exhibited a favorable safety profile and reduced the incidence of cSCC.

Melanoma patients with BRAF mutations have a poor prognosis, which has long been a challenging clinical issue. The emergence of combined targeted therapy with BRAF and MEK inhibitors has brought new hope to these patients. Dual-targeted therapies will soon become available in China. We look forward to more studies based on the Chinese population in the future, which will help continuously optimize targeted treatment strategies for BRAF-mutant melanoma and promote the clinical application of targeted drugs, thereby better serving the broad patient population.

CStone Pharmaceuticals’ satellite symposium showcased the latest advances in pan-cancer treatment with a novel RET inhibitor. It is understood that no selective RET inhibitors are currently marketed worldwide.

In the ARROW and LIBRETTO-001 clinical trials targeting RET fusion genes, BLU-667 and LOXO-292 have both achieved significant breakthroughs, prompting a shift in the design paradigm of clinical studies focused on rare driver genes. Basket and umbrella trial designs are expected to become the primary approach for future study protocols investigating novel therapeutics for rare genetic alterations.

Among them, BLU-667 is an oral, potent, and highly selective RET inhibitor developed by Blueprint Medicines. At this year’s ASCO Annual Meeting, the latest data from the ARROW study demonstrated that BLU-667 exhibits potent, durable, and broad antitumor activity, showing favorable clinical activity and tolerability in patients with advanced non-small cell lung cancer (NSCLC) harboring RET fusions, as well as in patients with advanced medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC) carrying RET alterations. These findings offer hope for precision therapy in patients with RET-fusion NSCLC and other tumors with RET variants.

BLU-667 has also demonstrated potent and durable antitumor activity in patients with advanced medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) harboring RET alterations. Updated data from the ARROW study showed that among 32 evaluable MTC patients, the objective response rate (ORR) was 56%, and the disease control rate (DCR) reached 97%. The response rate to BLU-667 in MTC patients was independent of prior tyrosine kinase inhibitor (TKI) resistance or RET genotype. In MTC patients previously treated with cabozantinib or vandetanib, the ORR with BLU-667 was as high as 63%, with a DCR of 94%. Furthermore, in patients with RET fusion-positive PTC, the ORR with BLU-667 treatment reached 83%.

In June 2018, CStone Pharmaceuticals entered into an exclusive collaboration with Blueprint Medicines to vigorously advance the clinical development of BLU-667 in China. In March 2019, the National Medical Products Administration (NMPA) approved the Phase I clinical trial of the RET inhibitor BLU-667 in China. The first Chinese patient was dosed on August 12. We anticipate that the China cohort of the ARROW trial will yield results consistent with the global study, thereby enabling patients with RET-altered tumors in China to benefit from this therapy as early as possible.

This year marks the third year that the Chinese Society of Clinical Oncology (CSCO) has hosted a dedicated session on smart healthcare. The choice of themes also reflects the increasingly prominent role of smart healthcare in clinical oncology academic activities.

At the conference, LinkDoc Technology signed a strategic cooperation agreement with Hengrui Medicine, a leading domestic innovative pharmaceutical company, to launch the “Smart Neighbor Companion, Science Extends Wisdom Collection” project, along with the “Patient Service Sci-Tech Innovation Platform” projects. Under the agreement, Hengrui Medicine will collaborate with LinkDoc’s Linke DTP Pharmacy as a “Demonstration Site for the Patient Service Sci-Tech Innovation Platform” to carry out patient education, follow-up visits, and innovative scientific research across China. This initiative will facilitate the upgrade of Linke Smart Pharmacy’s 3.0 model into the first and only research-oriented pharmacy in China, making Linke Smart Pharmacy the only pharmacy in the industry conducting innovative Real-World Studies (RWS).

At the ZeroKe booth, attendees can experience the latest smart healthcare applications, including a one-stop intelligent medical research solution, an integrated platform for diagnosis, treatment, and research, an AI product suite covering the entire process of single-disease diagnosis and treatment, innovative real-world study tools, intelligent patient recruitment systems, a whole-course patient treatment management platform, Linke Smart Pharmacy, and real-world data insight solutions.

AstraZeneca also showcased its explorations into integrated diagnostic and therapeutic solutions, including promoting testing and precision therapy, at the CSCO conference. It is reported that as of June 2019, AstraZeneca’s Integrated Lung Cancer Diagnosis and Treatment Centers had been established in 68 hospitals across China; its precision diagnostics platform had been deployed in 350 hospitals and 25 regional testing centers, with 130,000 patients undergoing standardized EGFR testing for lung cancer. In conjunction with multidisciplinary team (MDT) workstations at 138 hospitals, a one-stop, multidisciplinary medical consortium focused on lung cancer has begun to take shape. Meanwhile, patient rehabilitation bases under the “Lung Yang Home” initiative have been launched in influential large and medium-sized cities nationwide, such as Shanghai and Shenzhen, providing comprehensive care for lung cancer patients throughout the pre-hospital, in-hospital, and post-hospital phases.

Furthermore, VCBeat observed at the exhibition that Roche had brought AR devices to its booth, allowing attendees to experience an immersive journey through new drug development and clinical trials.

With this, the 2019 CSCO Congress drew to a close. As the last group of attendees departed, Xiamen Island returned to its usual tranquility. Yet the pursuit of advances in oncology treatment by clinicians and pharmaceutical professionals remains unceasing; they continue to leverage their expertise in the quest for the most universally accepted therapeutic regimens.