ASCO, where are the hot spots at the forefront?
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, the American Society of Clinical Oncology (American Society of Clinical Oncology, ASCO) held its annual meeting in Chicago to introduce the latest research on cancer treatment to experts and scholars from all over the world. More than 5000 pieces of cutting-edge research will be shared at the conference. Among them, according to incomplete statistics, more than 38 Chinese pharmaceutical companies participated and released 100 + cutting-edge research results and clinical tracking data in different types of conferences and topics. These studies involved more than 80 drugs, covering more than 100 targets. Let's take a look at what are the outstanding frontier hot spots.
Mining PD-(L)1 + Scheme to Highlight Unique Clinical Value in Segmented Areas
the current domestic PD-1/L1 class antibody drug products competition is fierce, the domestic has been listed 13 models, 9 PD-1,4 PD-L1. It is increasingly difficult to follow the indication layout in areas where the first mover has established clinical and sales advantages. However, at the same time, due to the advantages of PD-1/L1 immunotherapy and its broad-spectrum anti-tumor characteristics, there are still many niche markets that have not been fully developed, such as some cancer types with unsatisfactory response, improvement of curative effect through combined drugs, and drug resistance of immunotherapy. If we grasp the clinical blank, we can achieve unique clinical value, and we will gain a firm foothold in the future commercial competition and get good development space. At the annual meeting, many enterprises showed their different PD-(L)1 + schemes and provided good research and development ideas.
PD1 + Chemotherapy:
Svolizumab combined with chemotherapy for first-line treatment of small cell lung cancer, breaking a new OS record
Fuhong Hanlin show that the median OS of the first-line treatment of extensive small cell lung cancer (ES-SCLC) combined with standard chemotherapy has been significantly prolonged by 4.5 months compared with the chemotherapy group, breaking the new OS record of ES-SCLC first-line treatment. The OS rate at 24 months is more than 5 times that of the chemotherapy group. It can be seen that compared with other similar immune first-line therapies, slulliumab brings a higher overall survival benefit.
PD1 + LAG3:
further improve the treatment of first-line metastatic non-small cell lung cancer
TACTI-002 is a collaboration between Immutep and Merck to study Immutep lead product candidate eftilagimod alpha versus Merck's KEYTRUDA® for first-and second-line treatment of patients with HNSCC or NSCLC. Its phase II clinical data show an ORR of 38.6 percent in first-line treatment of metastatic NSCLC patients (PD-L1 unselected population), and the LAG-3 combination regimen brings more significant clinical benefits than the K-drug monotherapy data.
PD1 + VEGFR2:
improves overall survival in ICI-resistant patients
Although PD-1/L1 inhibitors have been widely used to treat advanced NSCLC and have improved patient survival, patients will still develop resistance to drugs. How to overcome immune checkpoint inhibitor (ICI) resistance will be a major unmet clinical need in the future. Remosiximab targeting VEGFR2 can reduce the infiltration of inhibitory immune cells and increase mature dendritic cells, and the combination of PD-1 inhibitors is expected to overcome drug resistance by reducing tumor neovascularization and promoting the proliferation of inflammatory cytokines.
S1800A is a clinical study of ramosiximab + pembrolizumab (drug K) versus standard therapy in advanced immunotherapy-resistant NSCLC. Phase II clinical data showed an overall survival (OS) of 14.5 months vs. 11.6 months compared to the control group, with a manageable safety profile. In the future, patients with NSCLC resistant to first-line immunotherapy are expected to achieve further survival benefits through the combination therapy of ramosiumab.
PD-1 neoadjuvant treatment of dMMR rectal cancer to achieve complete remission rate
DNA mismatch repair deficiency (dMMR) is one of the main causes of rectal cancer, and its standard treatment is still neoadjuvant chemotherapy and resection of the rectum after surgery. At present, there are relatively few studies on PD-(L) 1 immunosuppressants in this field. At the ASCO annual meeting, GSK reported data from a phase II clinical study of its PD-1 monoclonal antibody dostarlimab in the treatment of patients with stage II/III rectal adenocarcinoma with dMMR deficiency. The data showed that 12 patients who completed treatment and received at least 6 months of follow-up had all achieved clinical complete remission (100 percent).
dMMR locally advanced rectal cancer is highly sensitive to PD1 monotherapy, and these patients are expected to achieve significant clinical benefits through PD-1 treatment in the future. At present, there are only 5 projects with dMMR tumor indications in China, and the competition is relatively moderate, and related enterprises can also obtain good development space.
Table 1: Domestic clinical research and development of PD-1/L1 antibodies against MSI-H or dMMR solid tumors
Source: Medicine Intelligence Network
ADC takes a different approach, breaks through the subdivision of indications and combined with PD1
ADC is known as the biological missile, the antibody part can achieve the precise positioning of the target cell, cytotoxicity can kill tumor cells, to achieve the effect of 1+1 is greater than 2, very advantageous. The global market for ADC products is about $2.5 billion in 2020 and is expected to grow to $21.1 billion in 2025. The compound growth rate is as high as 53%, and the market size will grow further as ADC drug technology changes.
, with the further understanding of ADC drugs in the market, a number of domestic enterprises have also begun to lay out, currently developing a total of 60 + ADC drugs, covering 20 + targets. Therefore, in the increasingly fierce competition, the ADC field is also looking for another way to explore the subdivision of indications or the combination with other monoclonal antibody drugs. This ASCO conference can see some cutting-edge project cases.
HER2-ADC localization of breast cancer patients with low expression, change the treatment of breast cancer
breast cancer is one of the most common cancers, with more than 200 million breast cancer diagnoses worldwide in 2020. At present, HER2 targeted drugs are mostly used in HER2 positive patients, but there is no sufficient effective treatment for patients with low expression of HER2. However, about half of breast cancer patients have low expression of HER2, which is still a potential market.
Dichi and AstraZeneca Enhertu of HER2-ADC drugs presenting results from a Phase III trial at the conference that showed better progression-free survival (PFS) and overall survival (OS) in treated HER2-low unresectable or negative breast cancers compared with standard therapy. The risk of death was reduced by 49%, and OS was 5 months higher than chemotherapy.
Enhertu in HER2 low expression breast cancer patients provide a new treatment standard for about half of breast cancer patients, and the market space is broad. At the same time, Enhertu has also begun to carry out clinical trials in China. If it is successfully approved for listing in China, it will also form a strong competition for domestic ADC companies.
Table 2: Overview of domestic R & D progress in Enhertu
Source: Medicine Intelligence Network
ADC Breakthrough Urothelial Cancer, Open up Blue Ocean Indications
Vidicetuzumab is the first ADC drug listed by Rongchang Bio in China. At the ASCO conference, Rongchang Bio further discussed the effectiveness and safety of three studies of Vidicetuzumab in the treatment of metastatic urothelial cancer. Brings a different perspective to the treatment of this indication.
was the combination of treprozumab PD1 in the treatment of urothelial cancer, and the included cases showed excellent anti-tumor effect from both cORR and mPFS results.
the second study, a clinical trial of efficacy in HER2-negative patients with advanced urothelial cancer, phase II data showed that patients with advanced urothelial cancer had an objective response rate of 26.3 percent and a disease control rate of 94.7 percent. The median overall survival was 16.4 months. Vidicetuzumab has been shown to still benefit from treatment in some HER2-negative patients.
the third study was in patients with HER2-overexpressing urothelial carcinoma, updated clinical trial data showed sustained prolongation of mOS. It can be seen that patients with overexpression can also achieve long-term survival benefits, and drug safety can be controlled.
At present, the number of HER2-ADC carrying out clinical research on urothelial cancer is small. In addition to Rongchang Biology, there are also Korenbotai and Meiyake. Compared with HER2-positive breast cancer, gastric cancer and other popular large cancer species white-hot competition situation, urothelial cancer is a clinical treatment program more blank niche market, the layout of the track of the enterprise has a better business competition environment.
Emerging Targets Lead New R & D Direction
In recent years, the rapid development of the monoclonal antibody market has also made biopharmaceutical companies appear in some homogeneous targets, and emerging tumor immune targets have become a "new continent". At this ASCO annual meeting, many emerging biotechnology companies also released their latest clinical data on some new targets.
Junshi BTLA
B and T lymphocyte attenuator (BTLA), as an immune checkpoint molecule, has similar structure and intracellular signaling mechanism with other immune checkpoint molecules such as PD-1 and CTLA-4. At this annual meeting, Junshi Bio announced the results of its self-developed recombinant humanized IgG4 monoclonal antibody Icatolimab targeting BTLA, the results of a phase 1a study in patients with advanced solid tumors as a single agent, and the results of a phase 1 study in the treatment of relapsed/refractory lymphoma as a single agent or in combination with triprimab. The results of the study showed preliminary clinical efficacy as a monotherapy. The combination with PD1 was also well tolerated and showed preliminary clinical efficacy in patients with relapsed/refractory lymphoma.
Cinda LAG-3
Xinda Biology released the updated Phase 1b clinical data at this year's ASCO annual meeting. It shows that in the two cancer types of gastric and gastroesophageal junction cancer and squamous non-small cell lung cancer, whether LAG-3 monoclonal antibody is used alone or in combination with PD1 monoclonal antibody of Xinda, it shows good antitumor activity and controllable safety.
Celestial Creatures CD73
Tianjing Bio has published its CD73 eulelizumab combined with treplimab for the treatment of non-small cell carcinoma (NSCLC) Phase 2 clinical data, and eulelimab monotherapy or combination shows good safety and tolerance. In the three subgroups of NSCLC patients with different treatment situations, a positive efficacy signal was observed in patients with advanced NSCLC among whom standard treatment was not appropriate. The efficacy response was confirmed to be highly correlated with tumor CD73 expression, suggesting that CD73 may serve as a predictive biomarker.
innovation is an eternal theme. From the clinical research released at this ASCO conference, domestic enterprises are actively seeking innovation while experiencing homogeneous competition, including exploring niche markets for new indications for existing targets, combining different targets to enhance efficacy and safety, and exploring some emerging blue ocean targets. In the future, homogeneous competition will continue to heat up, with differentiated targets, medication methods or indications, in order to create unique clinical value, and only such enterprises can go further.
