ASCO 2026 | CStone Presents Updated Clinical Data for CS2009 (PD-1/VEGF/CTLA-4 Trispecific Antibody), Reinforcing Triple-Target Synergy and Delivering Strong Proof-of-Concept

ASCO 2026 | CStone Presents Updated Clinical Data for CS2009 (PD-1/VEGF/CTLA-4 Trispecific Antibody), Reinforcing Triple-Target Synergy and Delivering Strong Proof-of-Concept

First-line NSCLC – Compelling Activity Across All PD-L1 Subgroups
In first-line non-small cell lung cancer (NSCLC) patients with high PD-L1 expression (TPS ≥50%), CS2009 monotherapy achieved an objective response rate (ORR) of 81.3% and a disease control rate (DCR) of 100.0%, with consistent benefit across squamous (ORR: 87.5%) and non‑squamous (ORR: 75.0%) histologies. In the PD-L1-negative/low  population (TPS ≤5%) squamous NSCLC cohort, CS2009 in combination with chemotherapy achieved an ORR of 75.0% and a DCR of 100.0%; notably, PD-L1-negative patients within this cohort achieved an ORR of 100.0%; the current efficacy readout remains immature due to the short follow‑up for most patients in this cohort.

Later-line NSCLC – Potential to Overcome Immunotherapy Resistance
In heavily pretreated later-line NSCLC, CS2009 demonstrated encouraging antitumor activity, with most patients experiencing sustained tumor shrinkage. Across all dose levels, the 6-month duration of response (DOR) rate reached 85.7%. In the second-/third-line combination cohort, CS2009 achieved an ORR of 66.7% and a DCR of 100.0%. In the 30 mg/kg monotherapy cohort, patients whose disease had progressed following prior immunotherapy (IO) plus platinum-based chemotherapy —— a setting with significant unmet medical need—achieved an ORR of 30.8% and a DCR of 84.6%.

"Cold Tumors" – Meaningful Activity in Immunotherapy-Refractory Settings
In "cold tumors" with limited immunotherapy responsiveness, CS2009 monotherapy produced a 25.0% ORR and 87.5% DCR in heavily pretreated proficient mismatch repair/microsatellite stable metastatic colorectal cancer (pMMR/MSS mCRC). A 66.7% ORR and 100.0% DCR were observed when CS2009 was combined with XELOX in first-line mCRC. The current efficacy readout remains immature due to the short follow‑up for most patients in these two CRC cohorts. Additional monotherapy activity was seen in soft tissue sarcoma (STS) and non‑clear cell renal cell carcinoma (nccRCC) (ORR 33.3% each), reinforcing CS2009's potential to remodel the tumor microenvironment.

Updated Safety Data – Favorable Profile Confirmed with Longer Follow-up
With extended follow-up since initial presentation at European Society for Medical Oncology (ESMO) Congress 2025, updated Phase I safety data further confirmed the well-tolerated profile of CS2009. Importantly, no excessive toxicities typically associated with CTLA-4/PD‑(L)1 combinations observed. Among heavily pretreated patients with advanced solid tumors, Grade ≥3 treatment‑related adverse events (TRAE) occurred in 24.6% of patients, immune‑related adverse events (irAE) in 12.7% , and TRAE possibly related to anti-VEGF in 5.1%. This favorable safety profile was consistently maintained across both monotherapy and chemotherapy combination cohorts in first-line NSCLC.

Next Step – Phase III Registrational MRCT Planned by Year-End
The ongoing global Phase I/II trial has enrolled nearly 300 patients across China and Australia, with U.S. Investigational New Drug (IND) clearance now obtained. CStone plans to initiate the first Phase III global multi‑regional registrational trial (MRCT) for CS2009 by the end of 2026.

SUZHOU, China, May 31, 2026 /PRNewswire/ -- CStone Pharmaceuticals ("CStone," HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of therapies for oncology, immunology, inflammation, and other key disease areas, today announced that multiple key clinical updates for its core asset CS2009 (a PD-1/VEGF/CTLA-4 trispecific antibody) were presented in two posters at the American Society of Clinical Oncology (ASCO) Annual Meeting, covering Phase I/II clinical data in first-line and later-line NSCLC and CRC patients, as well as mature Phase I data from longer follow-up in patients with advanced solid tumors.

Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, commented, "As the clinical evidence continues to mature, CS2009 has advanced beyond early mechanistic validation and preliminary efficacy exploration to deliver a compelling proof of concept (POC). We are encouraged by its consistently favorable safety profile, both as a monotherapy and in combination with chemotherapy, alongside broad antitumor activity across multiple treatment settings. CS2009 has demonstrated promising potential to address key challenges in cancer immunotherapy, including overcoming immunotherapy resistance and extending clinical benefit to tumor types that have historically shown limited responsiveness to immunotherapy. Robust antitumor activity has been observed across multiple cohorts, including both first-line and later-line NSCLC, as well as first-line and later-line pMMR/MSS mCRC. These data further validate the strength of CS2009's triple-target synergistic mechanism and support its potential to serve as a next-generation immunotherapy backbone. Importantly, the findings provide a strong foundation for our planned global Phase III registrational MRCT and reinforce our confidence that CS2009 could ultimately offer transformative treatment options for patients with lung cancer, colorectal cancer, and a broad range of solid tumors."

Key Highlights of the Poster Presentations：

Non-Small Cell Lung Cancer (NSCLC)

In the ongoing Phase I/II study, CS2009 was evaluated as monotherapy or in combination with chemotherapy in advanced NSCLC patients without actionable oncogenic alterations. A total of 108 patients were enrolled across four groups:

(1) Group 1 (≥2L NSCLC monotherapy), n=57: CS2009 was dosed at 10–45 mg/kg, once every 3 weeks (Q3W);

(2) Group 2 (2/3L NSCLC combination therapy), n=9: CS2009 was dosed at 20 or 30 mg/kg, Q3W plus docetaxel;

(3) Group 3 (1L NSCLC monotherapy ), n=23: CS2009 was dosed at 20 or 30 mg/kg, Q3W;

(4) Group 4 (1L squamous NSCLC combination therapy), n=19: CS2009 was dosed at 20 or 30 mg/kg Q3W plus paclitaxel/carboplatin, followed by CS2009 maintenance therapy.

1. Baseline Patient Characteristics

In Group 1 (≥2L NSCLC monotherapy), 61.4% had received one prior line of therapy, 21.1% two lines, and 17.5% three or more lines. In Group 2 (2/3L NSCLC combination therapy), all patients had received one prior line of therapy.

2. Robust Efficacy*

(1) Group 3 (1L NSCLC monotherapy, PD-L1 high expression TPS ≥50%, n=16):

ORR was 81.3% (13/16) with a DCR of 100.0% (16/16); response rates were comparable in squamous (ORR: 87.5%, 7/8) and non-squamous (ORR: 75.0%, 6/8) histologies.

(2) Group 4 (1L squamous NSCLC combination therapy, PD-L1 negative or low expression TPS ≤5%, n=8):

• ORR was 75.0% (6/8) and DCR 100.0% (8/8); notably, the ORR in the PD-L1 TPS <1% subgroup reached 100.0% (4/4).

(3) Group 1 (≥2L NSCLC monotherapy, most IO pretreated, n=54):

• Across dose levels: Most patients showed sustained tumor shrinkage; median DOR was not reached, and the 6‑month DOR rate was 85.7%.
• At 30 mg/kg: ORR was 24.0% (6/25) and DCR 60.0% (15/25); median DOR was not reached, with a 6‑month DOR rate of 80.0%. For patients who had received only prior immunotherapy plus platinum-doublet chemotherapy (n=13), ORR rose to 30.8% (4/13) and DCR to 84.6% (11/13).

(4) Group 2 (2/3L NSCLC combination therapy, n=6):

• ORR was 66.7% (4/6), and DCR was 100% (6/6).

3. Favorable Safety and Tolerability

(1) Group 1 (≥2L NSCLC monotherapy): The incidence of Grade ≥3 TRAE, irAE, and TRAE possibly related to anti-VEGF therapy were 19.3%, 12.3%, and 5.3%, respectively;

(2) Group 2 (2/3L NSCLC combination therapy): The incidence of Grade ≥3 TRAE was 44.4%, with no Grade ≥3 irAE or TRAE possibly related to anti-VEGF therapy observed;

(3) Group 3 (1L NSCLC monotherapy): The incidence of Grade ≥3 TRAE was only 4.3%, with no TRAE possibly related to anti-VEGF therapy observed;

(4) Group 4 (1L squamous NSCLC combination therapy): The incidence of Grade ≥3 TRAE and irAE were 26.3% and 10.5%, with no TRAE possibly related to anti-VEGF therapy observed.

Metastatic Colorectal Cancer (mCRC)

1. Later-line mCRC Monotherapy Cohort: 14 heavily pretreated patients with mCRC, mostly pMMR/MSS, received CS2009 30 mg/kg monotherapy. Among efficacy-evaluable patients (n=8), ORR was 25.0% (2/8) and DCR was 87.5% (7/8).

2. 1L mCRC Combination Therapy Cohort: 14 treatment-naïve mCRC patients, mostly pMMR/MSS, received CS2009 30 mg/kg plus XELOX. Safety data showed Grade ≥3 TRAE in 14.3%, irAE in 7.1%, and TRAE possibly related to anti-VEGF in 14.3% (all grade 1–2, isolated events). In patients with at least one post-baseline tumor assessment (n=6), ORR reached 66.7% (4/6) and DCR was 100.0% (6/6).

Phase I Dose Escalation in Advanced Solid Tumors: Safety, Efficacy, and PK/PD Characteristics

1. Baseline Patient Characteristics

A total of 118 heavily pretreated patients with advanced solid tumors were enrolled in the dose-escalation phase across six dose levels (1–45 mg/kg). Among them, 50.8% had prior immunotherapy and 45.8% prior anti‑angiogenic therapy.

2. Favorable Safety and Tolerability

(1) Dose escalation of CS2009 has been completed, with no Dose-Limiting Toxicities (DLTs) observed and Maximum Tolerated Dose (MTD) not reached;

(2) The incidence of Grade ≥3 TRAE, irAE, and TRAE possibly related to anti-VEGF therapy were 24.6%, 12.7%, and 5.1%, respectively. The incidence of infusion-related reactions was 4.2%, all grade 1-2 and manageable.

3. Overall Phase I Efficacy as Expected; Meaningful Signal in "cold tumors"

(1) In the overall efficacy-evaluable population (n=104), ORR was 17.3% (18/104) and DCR was 70.2% (73/104); median DOR was not reached, and the 6‑month DOR rate was 77.4%. At 20 mg/kg and 30 mg/kg, ORRs were 13.3% (4/30) and 22.7% (10/44), respectively, with DCRs around 70%.

(2) In addition to CRC, CS2009 monotherapy has also demonstrated encouraging antitumor activity in later-line 'cold tumors' that are insensitive to PD-(L)1, such as STS and nccRCC:

• STS (n=12): ORR 33.3% (4/12), DCR 66.7% (8/12);
• nccRCC (n=6): ORR 33.3% (2/6), DCR 100.0% (6/6).

4. Excellent PK/PD Characteristics

(1) CS2009 demonstrated linear PK with a half-life of 6-9 days, supporting Q3W dosing. No significant accumulation was observed at Cycle 3. The incidence of anti-drug antibody (ADA) positivity was extremely low at only 0.7% (1/139).

(2) PD profile demonstrated saturated receptor occupancy and robust T-cell activation/proliferation confirming PD-1/CTLA-4 blockade and deep and sustained VEGFA neutralization.

• Receptor occupancy (RO) of PD-1/CTLA-4 on peripheral T cells reached saturation throughout the dosing interval at doses ≥20 mg/kg.
• On cycle 1 day 8, CS2009 induced notable, dose-dependent upregulation of Ki67 (proliferation due to PD-1 and CTLA-4 blockade) and ICOS (activation due to CTLA-4 blockade) expression on both CD4+ and CD8+ T cells, collectively demonstrating effective PD-1 and CTLA-4 inhibition by CS2009.
• Serum-free VEGFA reduced deeply and rapidly across all dose levels, and the effect sustained throughout dose intervals.

CStone will continue Phase II dose expansion in selected tumor types for dose optimization and to generate data as monotherapy or in combinations, supporting registrational trials in NSCLC, CRC and other indications. The first Phase III global MRCT is expected to be initiated by the end of 2026.

About CStone

CStone (HKEX: 2616), established in late 2015, is an innovation-driven biopharmaceutical company focused on the research and development of therapies for oncology, immunology, inflammation, and other key disease areas. Dedicated to addressing patients' unmet medical needs in China and globally, the Company has made significant strides since its inception. To date, the Company has successfully launched 4 innovative drugs and secured approvals for 21 new drug applications covering 9 indications. The company's pipeline is balanced by 16 promising candidates, featuring antibody-drug conjugates (ADCs), multispecific antibodies, immunotherapies and precision medicines. CStone also prides itself on a management team with comprehensive experiences and capabilities that span the entire drug development spectrum, from preclinical and translational research to clinical development, drug manufacturing, business development, and commercialization.

For more information about CStone, please visit: www.cstonepharma.com.

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