ASCO 2026: New Breakthrough in Pancreatic Cancer Immunotherapy, Spevatamig by PharmaEssentia Paves a New Treatment Path
From May 29 to June 2, 2026, local time, the 62nd Annual Meeting of the American Society of Clinical Oncology (ASCO) was held at the McCormick Place Convention Center in Chicago.
As the top academic event in the global oncology field, the annual ASCO meeting is the vane and origin of new cancer drug development and clinical innovation. At present, when the global trading ability and topic popularity of Chinese innovative drug assets are continuously rising, the importance of ASCO, the world's largest stage, is even greater than before.
This year's ASCO has also become a microcosm of Chinese innovative drugs transitioning from followers to rule - makers, and the innovation ability of the Chinese pharmaceutical industry has subverted multiple cancer treatment fields. For example, as the second Chinese innovative drug in history to enter the plenary session of ASCO, the Phase III HARMONi - 6 study of Kangfang Biotech's Ivonescimab is expected to reshape the global standard for first - line lung cancer immunotherapy and become a new therapy to change clinical practice. The updated results of Rongchang Biotech's Vedotin for the first - line treatment of HER2 - expressing locally advanced or metastatic gastric cancer, and the randomized controlled study of Hutchison China MediTech's Fruquintinib combined with chemotherapy as second - line treatment for metastatic colorectal cancer are targeting the new clinical guidelines for gastric cancer and colorectal cancer.
Arterynet noticed that at this year's ASCO, Chinese innovative pharmaceutical companies made a strong attack in the field of pancreatic cancer, advancing simultaneously in targeted therapy, ADC, and immunotherapy, forming a siege on the "king of cancers".
Expansion of the Treatment Map for the "King of Cancers"
At the beginning of 2026, the acquisition news of Revolution Medicines with AbbVie and Merck successively left a very lively start for the innovative drug industry and set the tone for the whole - year popularity of the RAS target. At the ASCO plenary session on May 31, Revolution Medicines disclosed the complete data of the Phase III randomized controlled study RASolute 302 of the pan - RAS inhibitor Daraxonrasib (RMC - 6236). This is probably the most concerned research result at this year's ASCO.
The data shows that in patients with previously treated metastatic pancreatic ductal adenocarcinoma, the median overall survival (mOS) in the Daraxonrasib group reached 13.2 months, while that in the chemotherapy group was 6.7 months, with a 60% reduction in the risk of death. Doubling the mOS is the most powerful Phase III positive data for pancreatic cancer targeted therapy to date. In addition, Hengrui Medicine's KRAS G12D inhibitor HRS - 4642, a domestic innovative drug, has become another targeted drug covering pancreatic cancer that has received much attention at this year's ASCO. The previous Phase I data showed that in 30 treatment - naive patients, the objective response rate (ORR) and disease control rate (DCR) of HRS - 4642 were 63.3% and 93.3% respectively, and the Phase III clinical trial has now been launched.
All along, pancreatic cancer has been one of the most difficult cancer types to be conquered by targeted drugs. Studies have shown that 90% of pancreatic cancer patients have mutations in the RAS gene, which has also become an ideal target for the development of new pancreatic cancer drugs. However, in the past two decades, no targeted drug targeting the RAS pathway has been able to obtain clinically meaningful OS data in pancreatic cancer. ASCO 2026 has broken this deadlock.
Another type of drug that has broken the deadlock in pancreatic cancer treatment is ADC. At this year's ASCO, the competitive landscape of pancreatic cancer ADC has even shifted from "single - product verification" to "multi - target parallel", and key clinical progress has been made in pipelines such as CLDN18.2 ADC, B7H3 ADC, and CEACAM5 ADC.
It is worth noting that at this year's ASCO, breakthroughs have also been made in the immunotherapy of pancreatic cancer. On the morning of May 30, Phanes Therapeutics presented the data of Spevatamig combined with the GnP regimen for the first - line treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC) at ASCO 2026 in a poster. As the world's first CLDN18.2/CD47 bispecific antibody to enter the clinical development stage, in the clinical trial of Spevatamig combined with GnP as first - line treatment for mPDAC at a low - dose regimen of 2 mg/kg weekly, the ORR and DCR of Spevatamig reached 52.4% and 90.5% respectively. In American patients, the median progression - free survival (mPFS) was 7.3 months, the median overall survival (mOS) was 14.7 months, and the median follow - up duration was 14.7 months, showing outstanding survival benefits. The data of Chinese patients are maturing. Spevatamig has a good safety profile. During the first - line treatment of mPDAC in combination with GnP, it has good tolerability. Compared with simple GnP chemotherapy, there is no obvious superimposed toxicity, and the safety window is excellent, which can support long - term use of combined chemotherapy. In addition, it is understood that the efficacy data of the high - dose group with 3 mg/kg weekly administration are continuously maturing, and this dose is expected to be the proposed administration dose for the subsequent Phase III registration clinical trial.
Arterynet learned that in the trial, more than 90% of the patients in this dose group were newly diagnosed metastatic cases, and the baseline characteristics were highly consistent with those of the international classic Phase III clinical trial population, laying the foundation for the subsequent clinical development.
At present, the clinical treatment of pancreatic cancer still mainly relies on traditional chemotherapy. The approved targeted and immunological drugs are few, and the applicable population is narrow, unable to cover most patients. There are obvious shortcomings in the drug treatment system. Even in the current era of rapid iteration of cancer treatment, the overall prognosis of pancreatic cancer patients is still very poor, and the survival benefits of advanced cases are very limited. At ASCO 2026, the clinical pipelines of targeted drugs, ADC, and immunotherapy have struggled to break through, forming a siege on the "king of cancers".
From Short - term Efficacy to Long - term Stability
Compared with the doubled mOS and significantly improved ORR brought by targeted therapies and ADC, the possibilities brought by pancreatic cancer immunotherapy may be even more exciting. If RAS targeted drugs and ADC solve the problem of "precision strike", immunotherapy is responsible for "holding on to the results".
In practice, although targeted drugs and ADC drugs can quickly act on tumor lesions and effectively inhibit tumor proliferation and control disease progression in the short term, they can never break through the core dilemma of drug resistance. Whether it is targeted drugs targeting KRAS and other targets or ADC drugs targeting new antigens, patients will almost always develop secondary drug resistance after long - term use, resulting in treatment failure, tumor recurrence and progression, making it difficult to achieve continuous tumor control, and ultimately unable to significantly prolong the overall survival of patients. This is also an unavoidable clinical limitation of targeted and ADC therapies in pancreatic cancer treatment.
Immunotherapy has a completely different underlying treatment logic. It does not directly kill tumor cells but activates and "trains" the patient's own immune system, enabling the body to independently identify and eliminate tumor cells and establish a long - term immune monitoring system. Relying on the unique immune memory and trailing effect, once immunotherapy takes effect, the remaining immune cells in the body can still identify and encircle the remaining tumor cells for a long time, continuously inhibiting tumor recurrence and metastasis, and can continuously bring long - term survival benefits to patients, effectively prolonging the overall survival. The Phase II data of Spevatamig combined with GnP for the first - line treatment of mPDAC show that the mPFS of American patients is 7.3 months and the mOS is 14.7 months, providing strong evidence of long - term survival benefits for the field of pancreatic cancer immunotherapy.
At the same time, different from targeted drugs and ADC drugs, which highly depend on specific tumor gene mutations and antigen expression and often have a limited beneficiary population, clinical regimens based on immunotherapy drugs can more flexibly expand the beneficiary population through diversified combination regimens, break through target limitations, and have broader clinical adaptability. For example, immune checkpoint inhibitors can form an efficient combination system with chemotherapy, targeted drugs, and ADC drugs, breaking through the limitations of cancer treatment and amplifying clinical efficacy through multiple mechanisms. Especially for pancreatic cancer, an immune - cold tumor, relying on the multi - target and multi - mechanism combination treatment mode can maximize the activation of the body's anti - tumor immune response, significantly improve the treatment efficiency, and also create a new path for breaking through the current clinical dilemma of pancreatic cancer.
However, the development of pancreatic cancer immunotherapy is extremely difficult, and there is still no clinically widely feasible treatment regimen. The reason behind this lies in the unique tumor microenvironment of pancreatic cancer, which forms a triple immune barrier and an independent and stubborn immune escape system.
The first is the immune cell deficiency barrier. Pancreatic cancer is a typical "cold tumor", and the infiltration ratio of killer CD8+ T cells in the tumor lesion is less than 5%. The mechanism of action of PD - 1/L1 inhibitors is to activate the existing infiltrating T cells. Without sufficient effector cells, the drugs are difficult to play a role. The second is the physical penetration barrier. A large number of activated pancreatic stellate cells and collagen fibers are enriched around the tumor, forming a dense fibrotic matrix, which greatly hinders drug delivery, resulting in most effective drugs being unable to reach the core of the tumor and the drug efficacy being greatly reduced. The third is the immune suppression barrier. A large number of inhibitory cells such as M2 macrophages and myeloid - derived suppressor cells are enriched in the lesion, continuously secreting inhibitory factors and comprehensively suppressing the body's anti - tumor immune response.
Therefore, traditional immunotherapy represented by PD - 1/PD - L1 inhibitors has struggled in pancreatic cancer. This also means that pancreatic cancer needs not an improvement of the existing immunotherapy path but a completely different new path from the underlying mechanism.
Spevatamig is an innate immunity enhancer (I2E), a type of emerging tumor immunological drug. Different from the currently widely used immune checkpoint inhibitors in clinical practice (such as anti - PD - 1/anti - PD - L1 drugs) that kill cancer cells by activating T cells, I2E identifies and eliminates cancer cells by activating macrophages and dendritic cells, providing a new alternative mechanism for using the body's own immune system to attack tumors, especially for so - called "cold tumors" that do not respond to immune checkpoint inhibitors. In the data announced at this ASCO, Spevatamig showed positive results at the first dose level for first - line pancreatic cancer, which means that the innate immune activation mechanism may bring new immunotherapy options for this "cold tumor" of pancreatic cancer.
A Bispecific Antibody to Solve the Dilemma of Pancreatic Cancer Immunotherapy
For the immunotherapy of pancreatic cancer, it is necessary to specifically solve the characteristics of the tumor microenvironment, rely on a new and differentiated mechanism and a customized combination regimen to promote research and development, which has also turned this field into a high - threshold and finely - divided hardcore innovation area.
Spevatamig of Phanes Therapeutics, as an immunotherapy drug, can achieve safe and controllable treatment of pancreatic cancer. The core lies in its differentiated dual - target molecular structure design. Spevatamig uniquely adopts the target design of CLDN18.2/CD47. Clinically, mPDAC tumor cells generally have the characteristic of over - expression of both CLDN18.2 and CD47, among which CD47 can activate the body's innate immune system and is a very promising anti - tumor target. However, drugs targeting CD47 or CLDN18.2 alone have obvious toxicity shortcomings, which seriously limit their clinical application.
Previously, limited by severe hematotoxicity, the clinical development of the CD47 pipeline was once difficult to advance. In 2024, Gilead's major CD47 pipeline Magrolimab was completely terminated due to safety issues. Clinical data showed that the incidence of drug - related adverse events of grade 3 and above of this drug was as high as 76.4%, far exceeding that of the control group. Severe hematotoxicity such as neutropenia, anemia, and thrombocytopenia occurred frequently, becoming a landmark setback in the development of the CD47 target. At the same time, CLDN18.2 - targeted drugs can cause stubborn gastrointestinal adverse reactions such as nausea and vomiting due to binding to normal gastric mucosa tissue. The toxicity problems of these two targets are the core bottlenecks restricting the implementation of dual - target drugs.
In the early development of Spevatamig, Phanes Therapeutics adopted a dual - exclusive molecular design. On the one hand, Phanes Therapeutics screened out the CD47 antibody PT240 with high tumor specificity. This subtype can strongly bind to tumor cells and greatly reduce the binding ability to red blood cells, avoiding hematotoxicity at the root. On the other hand, relying on the PACbody® and SPECpair® bispecific antibody platforms independently developed and designed by Phanes Therapeutics, Phanes Therapeutics built an asymmetric single - arm structure for Spevatamig, only retaining a single CLDN18.2 single - arm and a single CD47 single - arm, weakening the non - specific binding to normal tissues such as normal gastric mucosa and red blood cells, and precisely balancing efficacy and safety. The Spevatamig constructed by the above bispecific antibody platform is a natural IgG monoclonal antibody structure, with strong druggability and the ability to produce bispecific antibodies using traditional monoclonal antibody preparation processes, laying a solid foundation for subsequent commercial production.
At present, Spevatamig is simultaneously advancing Phase II clinical research in the United States and China, enrolling patients with unresectable locally advanced or metastatic gastric cancer, gastroesophageal junction cancer, pancreatic cancer, and biliary tract cancer. Previously, Spevatamig obtained the orphan drug designation for pancreatic cancer from the FDA in June 2022 and the fast - track designation for metastatic CLDN18.2 - positive pancreatic cancer from the FDA in March 2024. Completing the layout from orphan drug to fast - track in less than 2 years is not common among pancreatic cancer drugs, which means that Spevatamig is eligible to apply for priority review and rolling review in the subsequent NDA stage, which may shorten the time window from the completion of key clinical trials to the approval for marketing. The global clinical development strategy of Spevatamig not only significantly accelerates the patient enrollment progress but also accumulates key multi - regional and multi - ethnic data for subsequent efficacy verification in a broader population, paving the way for the company's future registration, application, and commercialization in the Chinese, American, and even global markets.
Currently, pancreatic cancer is undergoing a collective update of treatment logic. From targeted drugs and ADC drugs with rapid action to immunological drugs with long - term effects, for the first time, there is a possibility of perfecting the jigsaw puzzle of pancreatic cancer clinical treatment. Of course, the "king of cancers" status of pancreatic cancer will not change in the short term. But the direction of change is becoming clear: no longer a single - point breakthrough, but multiple paths in parallel, and each path is solving a piece of the pancreatic cancer treatment jigsaw puzzle.
This article is from the WeChat official account "Arterynet" (ID: vcbeat), author: Wang Shiwei, published by 36Kr with authorization.