Akeso's Cadonilimab (PD-1/CTLA-4 Bispecific) Enters MSKCC Phase II for HER2-Negative Gastric/GEJ Perioperative Treatment

Published: July 15, 2026 · Source: Akeso, Inc. press release, July 14, 2026 (Hong Kong) · Memorial Sloan Kettering Cancer Center collaboration announcement · COMPASSION-15 registration Phase III data · Akeso pipeline disclosures (2026)

Akeso, Inc. (HKEX: 9926.HK) announced on July 14, 2026 a Phase II clinical collaboration with Memorial Sloan Kettering Cancer Center (MSKCC) to evaluate cadonilimab — the world's first approved PD-1/CTLA-4 bispecific antibody — in combination with chemotherapy for the perioperative treatment of locally advanced, resectable HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. The trial is led by Dr. Yelena Janjigian, Chief of GI Medical Oncology at MSKCC and senior author of the CheckMate-649 trial that established PD-1 + chemotherapy as a global 1L standard. For international patients with gastric cancer — particularly the substantial cohort traveling from Indonesia, Vietnam, the Philippines, Russia, Kazakhstan, and the Gulf states to Chinese tertiary cancer centers — the story has two layers: the immediate MSKCC trial changes the US access picture, and the molecule behind it (cadonilimab) is already in routine Chinese clinical use and is the IO 2.0 backbone that Chinese oncology has been building toward for the last five years.

What cadonilimab is — and why PD-1/CTLA-4 bispecific is different from PD-1 alone

Cadonilimab (研发代号 AK104; 商标名 开坦尼) is Akeso's first-in-class PD-1/CTLA-4 bispecific antibody, developed on the company's proprietary Tetrabody platform. The molecule is a single IgG1 antibody with two distinct binding domains: one binds PD-1, the other binds CTLA-4. Mechanistically, this dual-target design aims to deliver stronger anti-tumor immune activation than either target alone — PD-1 blockade releases the brake on effector T cells, while CTLA-4 blockade amplifies the priming and expansion of those T cells in lymph nodes.

The clinical rationale for combining PD-1 and CTLA-4 blockade is well-established by the CheckMate-227 trial in lung cancer, where nivolumab (PD-1) + ipilimumab (CTLA-4) demonstrated superior long-term survival versus chemotherapy alone. But that combination has been limited in practice by overlapping toxicity: ipilimumab + nivolumab combinations show substantially higher rates of immune-related adverse events (irAEs) than PD-1 monotherapy, including colitis, hepatitis, and endocrinopathies. In gastric cancer, dual PD-1/CTLA-4 combinations have struggled to find a clinically usable efficacy-toxicity balance.

Cadonilimab's bispecific design attempts to resolve this. By concentrating both targets on a single molecule, the antibody preferentially engages PD-1 and CTLA-4 co-expressing T cells — which are most abundant in the tumor microenvironment — rather than peripheral T cells. The result, as reported in the COMPASSION-15 trial and earlier cadonilimab Phase II studies, is a dual-blockade efficacy signal with a tolerability profile closer to PD-1 monotherapy than to PD-1 + CTLA-4 combination therapy. The trade-off is the molecule's narrower immune-activation footprint compared to free ipilimumab + nivolumab; the gain is a clinically usable regimen in frail and elderly patients who would not tolerate the free-combination regimen.

Cadonilimab's structural design is not unique in the bispecific-immunotherapy space — AstraZeneca's volrustomig (PD-1/CTLA-4), Akeso's ivonescimab (PD-1/VEGF, also a Tetrabody product), and several other China-domestic candidates are in the same design class — but cadonilimab is the only one with NMPA approval in solid tumors as of mid-2026. That regulatory position is the reason the MSKCC collaboration matters: it is the first approved PD-1/CTLA-4 bispecific being deployed in a US investigator-led trial at a named US academic center, with a defined lead investigator (Janjigian) and a defined Phase II → Phase III path.

COMPASSION-15: the registration data that supports the MSKCC trial

COMPASSION-15 was the registration Phase III trial that supported cadonilimab's NMPA approval in 1L gastric/GEJ adenocarcinoma. The trial enrolled previously untreated patients with PD-L1-positive advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, randomized to cadonilimab plus XELOX chemotherapy (capecitabine + oxaliplatin) or placebo plus XELOX.

The published results showed statistically significant and clinically meaningful improvements in both overall survival and progression-free survival for the cadonilimab arm versus chemotherapy alone. The OS and PFS hazard ratios placed cadonilimab + XELOX in the same clinical-effect neighborhood as the CheckMate-649 nivolumab + chemotherapy regimen — which is the current global 1L standard — with a comparable or improved tolerability profile given the bispecific design. As of mid-2026, COMPASSION-15 is the registration dataset for cadonilimab in this indication in China; the FDA has not yet accepted the dataset for US registration (no BLA filing has been announced), and the MSKCC Phase II is, in effect, a US regulatory gate-keeping exercise for the molecule.

It is worth pausing on why this matters for international patients. The COMPASSION-15 data, the multiple China-domestic Phase III trials, and the MSKCC trial are all reading from the same playbook: the molecule has a clear clinical-effect signal in advanced disease, and the next question is whether earlier-line (perioperative) use lifts the long-term cure rate. The standard FLOT chemotherapy backbone in perioperative gastric/GEJ delivers a 3-year OS rate of approximately 48 percent; adding a PD-1 inhibitor to FLOT lifts the pathologic complete response (pCR) rate to approximately 19 percent. The MSKCC cadonilimab trial is designed to ask whether the PD-1/CTLA-4 dual blockade can lift pCR and OS meaningfully beyond the PD-1 + FLOT benchmark, with the CTLA-4 arm adding a depth of immune activation that PD-1 monotherapy does not.

The MSKCC Phase II trial design

The trial, as announced on July 14, 2026, is an investigator-led Phase II study at MSKCC. The principal investigator is Dr. Yelena Janjigian, MD, Chief of the Gastrointestinal Medical Oncology Service at MSKCC. Dr. Janjigian is the senior author of the CheckMate-649 trial (nivolumab + chemotherapy in 1L gastric/GEJ adenocarcinoma) and a globally recognized investigator in upper-GI cancers, particularly gastric and esophageal cancer. The trial will evaluate cadonilimab in combination with chemotherapy (the specific chemotherapy backbone is consistent with standard perioperative regimens, most likely FLOT) in patients with locally advanced, resectable HER2-negative gastric or GEJ adenocarcinoma — meaning patients who are candidates for curative-intent surgery but who have high-risk features (lymph node involvement, T3-T4 primary tumor, signet-ring or poorly differentiated histology) that make the 48 percent 3-year OS rate of FLOT alone insufficient.

The trial is actively enrolling patients at MSKCC and additional US sites. The primary endpoints are typically pathologic complete response (pCR) rate and major pathologic response (MPR) rate at the time of surgery, with secondary endpoints including event-free survival, overall survival, and safety/tolerability. The trial is designed to generate the clinical evidence that supports the future initiation of an international multicenter Phase III — which would be the registration path for cadonilimab in perioperative gastric/GEJ adenocarcinoma both in China and globally.

The strategic significance of the MSKCC trial is twofold. First, the data generated will support the design of an Akeso-led international Phase III, which is the FDA-acceptable registration path for the indication in the United States. Second, investigator-led trials at named US academic centers serve as the de facto regulatory gate-keeping exercise for the FDA — positive Phase II at MSKCC is a credible signal of US clinical traction in a way that a Chinese-domestic Phase III is not. For international patients with gastric cancer who are not US residents, the trial is indirect evidence that the molecule has a global development path; for US residents, it is direct access to cadonilimab before any FDA approval.

Akeso's broader IO 2.0 pipeline: cadonilimab is one of two flagship molecules

Cadonilimab is one of two flagship molecules in Akeso's IO 2.0 platform. The other is ivonescimab (PD-1/VEGF bispecific, also a Tetrabody product), which is the subject of the HARMONi-6 trial in 1L squamous non-small-cell lung cancer (the data was featured in the ASCO 2026 plenary session in early June 2026). Both molecules are increasingly being positioned as China-discovered IO 2.0 backbones for global combination studies — a meaningful shift from the previous narrative in which Chinese-discovered immuno-oncology assets were developed in China and licensed to Western pharma for further development.

The Akeso pipeline disclosure as of mid-2026 includes more than 50 innovative assets across cancer, autoimmune disease, inflammation, and metabolic disorders. Twenty-seven candidates are in clinical trials; 15 are bispecific or multispecific antibodies or bispecific ADCs; eight are at commercial stage. The platform technologies that support the pipeline — Tetrabody (bispecific antibody engineering), AI-powered drug R&D, Dual-Shield ADC, Dual-Lock T-cell engager, Tissue-Smart siRNA/mRNA — are all in-house, which is the structural reason the company can sustain a 50+ asset pipeline without a major licensing-out strategy.

For the international gastric cancer patient, the relevant slice of the pipeline is the cadonilimab Phase III program. Beyond COMPASSION-15 (1L advanced/metastatic gastric/GEJ, NMPA-approved) and the new MSKCC Phase II (perioperative gastric/GEJ), Akeso is also developing cadonilimab in hepatocellular carcinoma (COMPASSION-22, post-TKI setting), esophageal squamous cell carcinoma (1L), and additional combination programs. Two international Phase III trials are Akeso-led. The molecule is increasingly described in industry coverage as a "pipeline in a product" — the breadth of indication expansion is a deliberate strategy to establish cadonilimab as the IO 2.0 backbone for combination regimens across solid tumors.

How international patients access cadonilimab today

Cadonilimab is NMPA-approved in China for several indications, including 1L gastric/GEJ adenocarcinoma. For international patients with gastric or GEJ cancer who are candidates for cadonilimab + chemotherapy, the practical access path in mid-2026 is:

For US-resident patients with locally advanced HER2-negative gastric/GEJ adenocarcinoma, the MSKCC Phase II is now the only domestic access path to cadonilimab. The trial is enrolling at MSKCC and additional US sites — interested patients should contact MSKCC's Gastrointestinal Medical Oncology Service for trial enrollment details. The trial is the first US clinical access point for any PD-1/CTLA-4 bispecific in gastric cancer.

For patients from Indonesia, Vietnam, the Philippines, Russia, Kazakhstan, the Gulf states, and other high-burden markets who travel to China for treatment, the picture is the opposite: cadonilimab is in routine Chinese clinical use today, and the MSKCC trial is primarily a US-access development step rather than a Chinese-access development step. The practical questions for these patients are whether cadonilimab + chemotherapy is appropriate for their disease setting (1L, perioperative, later-line), what the out-of-pocket cost is at a Chinese tertiary center (typically $5,000-$15,000 per cycle for cadonilimab + chemotherapy, depending on the regimen and the hospital), and whether the indication is among the NMPA-approved set or is available only on a clinical-trial basis.

What to ask at consultation

For international patients considering cadonilimab + chemotherapy for gastric or GEJ cancer, the following questions are worth bringing to a Chinese tertiary-center consultation:

1. What is my HER2 status, PD-L1 CPS, and MSI/dMMR status? Cadonilimab is currently NMPA-approved in 1L gastric/GEJ adenocarcinoma regardless of PD-L1 status in the COMPASSION-15 indication, but PD-L1 CPS score and MSI/dMMR status affect response durability and the choice between cadonilimab and alternative backbones.
2. Is my case perioperative, 1L advanced, or later-line? The MSKCC Phase II targets perioperative (resectable) disease; the COMPASSION-15 registration covers 1L advanced/metastatic disease. The treatment setting changes the regimen, the duration, and the cost profile.
3. What is the surgery plan, and is it a curative-intent resection? Perioperative immunotherapy is given around a planned curative-intent resection. The MDT (medical oncology + surgical oncology + radiation oncology) review at a Chinese tertiary cancer center is the right setting for this decision.
4. What is the recommended chemotherapy backbone? In 1L advanced disease, XELOX (capecitabine + oxaliplatin) is the COMPASSION-15 backbone; in perioperative disease, FLOT (5-FU + leucovorin + oxaliplatin + docetaxel) is the standard. The chemotherapy choice affects tolerability and out-of-pocket cost.
5. What is the irAE (immune-related adverse event) monitoring plan? Cadonilimab has a tolerability profile closer to PD-1 monotherapy than to PD-1 + CTLA-4 combination, but irAEs still occur. The Chinese tertiary center should have a clear irAE-management protocol including thyroid, hepatic, pulmonary, and GI monitoring.
6. What is the total estimated out-of-pocket cost for the planned regimen? Cadonilimab + chemotherapy at a Chinese tertiary center typically runs $5,000-$15,000 per cycle, with 4-6 cycles in the perioperative setting and ongoing cycles in 1L advanced disease. International patient offices can provide a written estimate before treatment starts.
7. Is the indication NMPA-approved, or is the regimen available only on a clinical-trial basis? NMPA-approved indications (1L gastric/GEJ adenocarcinoma, recurrent cervical cancer, hepatocellular carcinoma) are commercially available at all NMPA-licensed cancer centers. Off-label use (e.g., perioperative gastric/GEJ) may be available only on a clinical trial or on a named-patient basis; the hospital's ethics committee and the regulatory pathway should be clarified before treatment starts.

Bottom line

The July 14, 2026 MSKCC collaboration is a meaningful step in cadonilimab's global trajectory, and it places Akeso's PD-1/CTLA-4 bispecific in the same clinical-investigation framework that previously validated PD-1 inhibitors in the same disease setting. For US-resident patients with locally advanced HER2-negative gastric or GEJ adenocarcinoma, the MSKCC Phase II is the first domestic access point. For international patients traveling to China for treatment, the story is a confirmation of what is already in routine Chinese clinical use: cadonilimab + chemotherapy is the standard 1L backbone for PD-L1-positive gastric/GEJ adenocarcinoma in China, supported by COMPASSION-15 data and a multi-indication development program that includes 12+ Phase III trials globally.

For readers planning medical travel to China for gastric cancer treatment, the practical access to cadonilimab is already there — the MSKCC trial is a US clinical-development step, not a Chinese-access gate. The decisions that matter for the individual patient are the indication match (is the case NMPA-approved for cadonilimab?), the regimen backbone (XELOX vs FLOT vs other), the irAE monitoring plan, and the total out-of-pocket cost. These are the questions to bring to a Chinese tertiary-center MDT consultation; the rest of the cadonilimab story will play out at MSKCC, Akeso's international Phase III, and the FDA over the next 2-3 years.