On May 31, 2026 D3 Bio Inc., a global clinical-stage biotechnology company dedicated to developing innovative oncology therapeutics, reported first-line (1L) clinical data of elisrasib monotherapy and elisrasib in combination with pembrolizumab from an ongoing Phase I/II study of elisrasib (D3S-001), its next-generation KRAS G12C inhibitor, in patients with KRAS G12C mutation–positive (G12Cmut) non–small cell lung cancer (NSCLC). The data were presented in a Clinical Science Symposium at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois.

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Findings from both cohorts, which demonstrate favorable safety and tolerability profiles along with highly promising antitumor activity in 1L G12Cmut NSCLC across all levels of PD-L1 expression, support continued evaluation of elisrasib in the first-line setting.

Elisrasib as First-Line Monotherapy for Patients with KRAS G12C Mutation–Positive NSCLC

Elisrasib monotherapy demonstrated highly promising preliminary antitumor activity. Forty-three patients with previously untreated G12Cmut NSCLC received elisrasib 600 mg once daily in 21-day cycles, with a median study follow-up of 8.5 months. In 41 efficacy-evaluable patients, the overall response rate (ORR) was 78.0% was observed across all levels of PD-L1 expression, with 76.2% ORR in patients with PD-L1 TPS <1% (N=21) and 80.0% in patients with PD-L1 TPS of ≥1% (N=20), respectively. The disease control rate (DCR) was 95.1%. The median progression-free survival (mPFS) was 12.4 months (95% CI: 6.8, NR), with a 12-month PFS rate of 50.8%. Median overall survival (OS) was not reached, with a 12-month OS rate of 90.0%. As of the data cutoff, 60.5% of patients remained on study treatment.

Elisrasib monotherapy was well tolerated, with Grade 3 or higher TRAEs observed in only 7% of patients and serious TRAEs in 2.3% of patients. No TRAEs led to elisrasib discontinuation, and no dose reductions were required.

Elisrasib plus Pembrolizumab as First-Line Combination Therapy for Patients with KRAS G12C Mutation–Positive NSCLC

Fifty-two patients with previously untreated G12Cmut NSCLC received elisrasib 600 mg once daily in combination with pembrolizumab 200 mg every 3 weeks (Q3W), with a median study follow-up of 5.7 months. Notably, the dose of elisrasib used in combination is elisrasib’s RP2D at 600mg QD which provides complete KRAS G12C target coverage.

The combination of elisrasib and pembrolizumab showed highly compelling antitumor activity in patients with previously untreated G12Cmut NSCLC. In 48 efficacy-evaluable patients, an ORR 81.3% was observed across all PD-L1 expression levels, with ORR of 70.6% in patients with PD-L1 TPS <1% (N=17), 72.7% in patients with PD-L1 TPS of 1% to 49% (N=11), and 95.0% in patients with PD-L1 TPS ≥50% (N=20), respectively. The overall DCR was 97.9%. The median PFS was not reached (95% CI: 8.4, NR), with a 6-month PFS rate of 74.6% and a 12-month PFS rate of 53.7%. Median OS was not reached, with a 12-month OS rate of 88.8%. As of the data cutoff, 82.7% of patients remained on study treatment.

The combination regimen demonstrated a safety profile consistent with the known profiles of each agent. Grade 3 or higher TRAEs occurred in 32.7% of patients, with most severe events attributable to pembrolizumab, and serious TRAEs reported in 17.3% of patients. No new or unexpected safety signals were identified for elisrasib, and the overall safety profile compared favorably with the established standard-of-care regimen of pembrolizumab plus chemotherapy.

Expert Commentary

Prof. Shun Lu, M.D., Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, and lead study presenter, said: "The first-line results for elisrasib are very encouraging, showing strong and consistent antitumor activity across PD-L1 expression subgroups, both monotherapy and in combination with pembrolizumab. Its favorable tolerability and rapid response onset further highlight its potential as a promising treatment option for patients with KRAS G12C-mutant NSCLC."

"The compelling activity of elisrasib as monotherapy and in combination with pembrolizumab observed in the first-line NSCLC represents an exceptionally promising signal in this historically difficult-to-treat population," said Dr. George Chen, Founder, Chairman, and Chief Executive Officer of D3 Bio. "We believe these results support the continued and accelerated evaluation of elisrasib in Phase 3 randomized studies."

About Elisrasib (D3S-001)

Elisrasib is a next-generation KRAS G12C inhibitor designed for rapid, complete, and selective target engagement. It covalently binds the GDP-bound (OFF) form of KRAS G12C, effectively blocking nucleotide cycling and suppressing oncogenic signaling. Preclinical studies show robust potency, complete KRAS G12C engagement at clinically relevant exposures, and CNS penetration capability. Elisrasib is currently being evaluated globally in a Phase 2 monotherapy and combination trial across KRAS G12C–mutant solid tumors including NSCLC, CRC, and others.

(Press release, D3 Bio, MAY 31, 2026, View Source [SID1234666264])

On May 31, 2026 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, reported 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) (Free ASCO Whitepaper) 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.

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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.

*Note: Efficacy analyses were performed only in patients who received at least one post‑baseline tumor assessment. The number of such patients is less than or equal to the total number of patients enrolled in the group.

(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).
*Note: Efficacy analyses were performed only in patients who received at least one post‑baseline tumor assessment. The number of such patients is less than or equal to the total number of patients enrolled in the group.

(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).
*Note: Efficacy analyses were performed only in patients who received at least one post‑baseline tumor assessment. The number of such patients is less than or equal to the total number of patients enrolled in the group.

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).

*Note: Efficacy analyses were performed only in patients who received at least one post‑baseline tumor assessment. The number of such patients is less than or equal to the total number of patients enrolled in the group.

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).

*Note: Efficacy analyses were performed only in patients who received at least one post‑baseline tumor assessment. The number of such patients is less than or equal to the total number of patients enrolled in the group.

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.

(Press release, CStone Pharmaceauticals, MAY 31, 2026, View Source;cstone-presents-updated-clinical-data-for-cs2009-pd-1vegfctla-4-trispecific-antibody-reinforcing-triple-target-synergy-and-delivering-strong-proof-of-concept-302786438.html [SID1234666263])

On May 31, 2026 Oricell Therapeutics, a clinical-stage biotech company pioneering cancer immunotherapy, reported that its lead asset, Ori-C101, a GPC3-targeted CAR-T therapy, achieved a 66.7% objective response rate (ORR) in patients with Late-line refractory hepatocellular carcinoma (HCC). The data, selected for an oral presentation at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, highlight a potential new benchmark for patients who have exhausted standard therapies.

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Hepatocellular carcinoma (HCC) remains a critical global health challenge, particularly in China, which accounts for more than one-third of the world’s over 800,000 annual deaths from the disease. While frontline treatments have evolved, options for patients failing second-line therapy are scarce, with historical ORRs typically below 13%.

Oricell’s registrational Phase Ib BEACON study challenges this status quo. As of April 3, 2026, among 18 efficacy-evaluable patients with advanced, heavily pretreated HCC:

Overall ORR reached 50%.
At the Recommended Phase 2 Dose (RP2D), ORR surged to 66.7%, with a disease control rate (DCR) nearing 90%.
Durability was profound: One patient achieved a complete response (CR) lasting 24 months.
Safety was manageable: No immune effector cell-associated neurotoxicity syndrome (ICANS) or off-tumor toxicity was observed, with cytokine release syndrome (CRS) contained within controllable grades.
Long-Term Validation: From 2021 ASCO (Free ASCO Whitepaper) Poster to Registrational Data

Notably, as early as 2021, Oricell’s investigator-initiated trial (IIT) data for Ori-C101 were selected for a poster presentation at ASCO (Free ASCO Whitepaper). At that time, a striking response was observed in a late-line HCC patient following a single infusion: the first efficacy assessment showed a partial response (PR), with target lesions shrinking by 96.1% (from 155.45 mm to 6 mm) and alpha-fetoprotein (AFP) levels plummeting by 99.1% (from >80,000 ng/mL to 742 ng/mL). The patient achieved an overall survival (OS) of nearly three years.

The now-unveiled registrational clinical data further validate the clinical value of Ori-C101, reinforcing the consistency and reproducibility of Oricell’s approach from early proof-of-concept to pivotal trials.

Technology Backbone: A "Three-in-One" Engine Addressing Solid Tumor Barriers

Ori-C101’s exceptional performance stems from Oricell’s proprietary technology platforms, systematically addressing major challenges in CAR-T therapy for solid tumors: antigen heterogeneity, immunosuppressive tumor microenvironment (TME), and manufacturing efficiency.

1. OriAb (AI-Powered Antibody Discovery Platform）
The OriAb platform features a massive library comprising up to 10¹¹ fully human scFv and nanobody sequences. Utilizing a live-cell-based high-throughput screening strategy, the platform specifically identifies native conformational antigens, including challenging targets such as GPCRs, thereby avoiding the false-positive risks associated with purified protein-based screening. Furthermore, AI-assisted algorithms have compressed the antibody discovery and screening cycle from a traditional 12 months to just 3 months, significantly enhancing both efficiency and quality. The resulting high-specificity, optimally affine GPC3 antibody sequence equips Ori-C101 with a robust safety profile, effectively minimizing the risk of off-tumor toxicity.

2. OriArmoring (Structure-Enhanced Cell Platform)
The OriArmoring platform incorporates customized "armoring" elements designed to modulate T cell metabolic pathways and signal transduction based on the specific tumor microenvironment (TME). This engineering strategy enriches young, stem-like memory T cell subsets (Tscm), significantly enhancing the in vivo persistence of Ori-C101. By remodeling the local immune microenvironment, the platform effectively reverses immunosuppression, converting "cold tumors" into "hot tumors," thereby promoting the infiltration and activation of effector T cells. This approach overcomes the dual bottlenecks of the immunosuppressive TME and T cell exhaustion in solid tumors, ensuring durable, long-term responses. Additionally, the platform integrates logic-gating strategies—including ‘OR’ gating to prevent antigen escape and ‘AND’ gating to improve targeting precision—which collectively optimize the therapeutic index of the product.

3. OriOnGo: Flexible Manufacturing Platform (Classic / Rapid / In Vivo)
Built on a "Quality by Design" (QbD) philosophy, this platform includes proprietary manufacturing technologies. The rapid manufacturing process reduces ex vivo culture time to just 3 days, significantly improving productivity and lowering cost of goods (COGS). It ensures final product cell viability consistently above 95%, and compresses the vein-to-vein time to within 15 days. Moreover, the platform’s in vivo CAR-T product design and process capabilities open broader future applications for CAR-T therapy. This integrated manufacturing approach enables scalable, cost-effective production while maintaining product quality and patient access.

Executive Outlook

"Securing a third ASCO (Free ASCO Whitepaper) oral presentation validates our integrated platform strategy," said Dr. Helen Yang, Co-Founder and CEO of Oricell. "We are accelerating the pivotal Phase II development to bring this therapy to market. We are also actively seeking global partnerships to expand the reach of our technology and deliver hope to patients worldwide."

(Press release, OriCell Therapeutics, MAY 31, 2026, View Source;oricells-gpc3-car-t-ori-c101-hits-66-7-orr-in-late-line-hcc-signaling-best-in-class-potential-302786638.html [SID1234666262])

On May 31, 2026 Hanmi Pharm. Co., Ltd. ("Hanmi") reported that they have entered into a license agreement for the development, manufacturing and commercialization of Hanmi’s biologic drug candidate sonefpeglutide (LAPSGLP-2 analog) with Eli Lilly and Company ("Lilly").

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Sonefpeglutide is a novel drug candidate incorporating Hanmi’s proprietary long-acting platform technology, LAPSCOVERY. Hanmi has previously received FDA marketing approval for a biologic incorporating its LAPSCOVERY platform and is currently conducting additional global clinical trials for five other programs utilizing the same platform.

Hanmi has focused on the biological functions of glucagon-like peptide 2 (GLP-2) – including the promotion of intestinal growth, reduction of inflammation, and protection and regeneration of the intestinal mucosa – and has demonstrated these effects through a range of non-clinical studies. The company has also presented the therapeutic potential of LAPSGLP-2 across multiple indications at major scientific conferences. Hanmi is currently conducting a global Phase 2 clinical trial in short bowel syndrome (SBS).

Hanmi will continue to conduct the ongoing global Phase 2 trial in SBS through completion while Lilly will explore additional clinical trials for sonefpeglutide based on its nonclinical and clinical data.

Through this agreement, Lilly will obtain exclusive rights to develop, manufacture and commercialize sonefpeglutide worldwide, excluding Korea.

Juhyun Lim, Vice Chairman of Hanmi, stated, "It is highly meaningful that Lilly—one of the most closely watched innovators globally—has highly recognized the development potential for sonefpeglutide." She added, "Hanmi will continue to advance innovative drug development, guided by our mission of ‘Respect for People and Value Creation.’"

Under the agreement, Hanmi will receive an upfront payment of USD 75 million and may receive up to an additional USD 1.185 billion in clinical development, regulatory approval and commercialization milestone payments. In addition, Hanmi will be eligible to receive royalties following product launch.

(Press release, Hanmi, MAY 31, 2026, View Source [SID1234666261])

On May 31, 2026 Summit Therapeutics Inc. (NASDAQ: SMMT) reported positive overall survival (OS) results from the Phase III HARMONi-6 trial, conducted in China and sponsored by Summit’s partner Akeso, Inc. (HKEX Code: 9926.HK), will be presented today as part of the Plenary Session at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

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The presentation is entitled "Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in previously untreated advanced squamous non-small cell lung cancer: Overall survival results of the phase 3 HARMONi-6 trial." HARMONi-6 is evaluating ivonescimab in combination with platinum-based chemotherapy compared to tislelizumab, a PD-1 inhibitor, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) irrespective of PD-L1 expression. HARMONi-6 is a single region, multi-center, Phase III study conducted in China and sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso. The trial’s primary endpoint is progression-free survival (PFS), and OS is a key secondary endpoint.

The trial results will be presented by Dr. Shun Lu, MD, PhD, Chief of Shanghai Lung Cancer Center at Shanghai Chest Hospital, Professor of Medicine at Shanghai Jiaotong University, and associate editor for the Journal of Thoracic Oncology.

In major markets globally, first-line therapy for patients with advanced NSCLC without driver mutations is most commonly a PD-1 inhibitor plus platinum-based chemotherapy. Prior to HARMONi-6, there were no known Phase III clinical trials in advanced NSCLC which have shown a statistically significant and clinically meaningful improvement in OS when compared to PD-(L)1 inhibitor therapy in combination with chemotherapy in a head-to-head setting. Examples of PD-(L)1 inhibitors include pembrolizumab, nivolumab, tislelizumab, and atezolizumab.

Clinically Meaningful Efficacy

In the HARMONi-6 planned interim analysis of OS, ivonescimab in combination with chemotherapy demonstrated a statistically significant improvement when compared to tislelizumab in combination with chemotherapy, with a hazard ratio (HR) of 0.66 (95% CI: 0.50, 0.87; p=0.0017). A clinically meaningful benefit was demonstrated across clinical subgroups, including those with either PD-L1 negative or positive expression. OS rates at 24 months were 64.7% for those patients receiving ivonescimab plus chemotherapy compared to 48.6% for those receiving tislelizumab plus chemotherapy. Median follow-up time of the current data cut was 21.4 months.

HARMONi-6 ITT (n=532):

Median Follow-up: 21.36 mos.

Ivonescimab + Chemo

(n=266)

Tislelizumab + Chemo

(n=266)

Median OS

27.89 mos.

(95% CI: 27.89, NE)

23.69 mos.

(95% CI: 20.11, NE)

24-Month OS Rates

64.7%

48.6%

OS Stratified HR

0.66

(95% CI: 0.50, 0.87; p= 0.0017)

mos.: months; NE: not established

HARMONi-6 PD-L1 Subgroup Analyses

Ivonescimab + Chemo vs. Tislelizumab + Chemo

PD-L1 Negative (PD-L1 TPS <1%) OS stratified HR

Ivonescimab + Chemo n=105; Tislelizumab + Chemo n=105

0.64

(95% CI: 0.43, 0.96)

PD-L1 Positive (PD-L1 TPS >1%) OS stratified HR

Ivonescimab + Chemo n=161; Tislelizumab + Chemo n=161

0.68

(95% CI: 0.46, 0.99)

"For the first time, a Phase III clinical study has demonstrated a statistically significant overall survival benefit in front-line driver-mutation-negative non-small cell lung cancer compared to anti-PD-1 therapy in combination with chemotherapy," said Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit. "While this represents another study where ivonescimab has demonstrated a significant OS benefit, these data represent the answer to the question regarding ivonescimab and its ability to translate PFS benefits into the extension of lives for patients with cancer in the front-line setting compared to immunotherapy-based regimens."

The HARMONi-6 study met its primary endpoint as announced in April 2025, showing a statistically significant and clinically meaningful improvement in PFS. Detailed results for efficacy and safety were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2025 Congress (ESMO 2025) last October and published in The Lancet simultaneously.

Safety Profile

In this analysis, ivonescimab continued to demonstrate an acceptable and manageable safety profile in the HARMONi-6 study, which was consistent with previous Phase III studies of ivonescimab plus chemotherapy. No additional safety signals were noted in the HARMONi-6 study in this current data cut compared to the previous data cut presented.

Treatment-related serious adverse events occurred in 41.4% of patients receiving ivonescimab in combination with chemotherapy and 34.3% of patients receiving tislelizumab in combination with chemotherapy. Most of the possibly VEGF-related adverse events occurring in the ivonescimab-plus-chemotherapy arm were classified as Grade 1 or 2; Grade 3 or higher hemorrhage events were observed in 2.6% of patients in the ivonescimab-plus-chemotherapy arm compared to 0.8% of patients in the tislelizumab-plus-chemotherapy arm in this study. Treatment-related adverse events (TRAEs) leading to discontinuation in this study occurred in 5.3% of patients receiving ivonescimab plus chemotherapy compared to 4.5% for those receiving tislelizumab plus chemotherapy.

In squamous NSCLC, VEGF-A monoclonal antibodies have had limited clinical development based on historical data demonstrating significant risks of toxicity, including life-threatening hemorrhage and other bleeding complications. The results of this study further validate the unique mechanism of action of ivonescimab, including apparent key differences as compared to historical clinical studies where an anti-PD-1 monoclonal antibody and an anti-VEGF monoclonal antibody were administered separately.

HARMONi-6 Clinical Trial Results Published in The Lancet

The Lancet simultaneously published these findings in a manuscript titled, "Ivonescimab plus Chemotherapy for Squamous Non-small-cell Lung Cancer."

"A heartfelt congratulations to our partner, Akeso, for their continuing, tremendous efforts to make a significant difference in the lives of patients with cancer," said Robert W. Duggan, Chairman and Co-Chief Executive Officer of Summit. "The decision we made in December 2022 to enter into a partnership specifically with Akeso and accelerate the global clinical development plan of this potentially landscape-changing compound in ivonescimab is further validated with these groundbreaking results for patients facing high unmet medical needs. We look forward to continuing this positive momentum."

Conference Call

Summit will host a conference call and live webcast to discuss recent updates related to ivonescimab, including data released at ASCO (Free ASCO Whitepaper), on Monday, June 1, 2026, at 7:00 a.m. ET. Conference call and webcast information is accessible through the company’s website, www.smmttx.com. An archived edition of the webcast will be available on the website later in the day on Monday.

About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 outside of Summit’s license territories, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. By design, ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.

This is intended to differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Summit believes ivonescimab’s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, iScience, 2025). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, iScience, 2025) increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, side effects, and safety profiles associated with prior approved drugs to these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently utilized in multiple Phase III clinical trials. Over 4,000 patients have been treated with ivonescimab in clinical studies globally, and over 70,000 patients when considering those treated in a commercial setting in China, as noted by Akeso.

There are currently 15 Phase III clinical studies that are either announced, ongoing, or have been completed studying ivonescimab, four of which are Summit-sponsored global studies, one of which is a multiregional study sponsored by a cooperative group, and 10 of which are being or have been conducted in China by Akeso. Summit began its clinical development of ivonescimab in NSCLC, commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3. In 2025, Summit began enrolling patients in HARMONi-7. Summit expanded its Phase III clinical development program into CRC in the fourth quarter of 2025 by initiating enrollment in HARMONi-GI3.

HARMONi is a Phase III clinical trial is evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third-generation EGFR TKI (e.g., osimertinib). Detailed results of the study were provided in September 2025, and a Biologics License Application (BLA) was submitted to the United States Food and Drug Administration (FDA) for marketing authorization, which the FDA accepted for filing in January 2026; the goal Prescription Drug User Fee Act (PDUFA) date is November 14, 2026.

HARMONi-3 is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression. The clinical trial is evaluating the two histologies as individual, separately powered cohorts with independent statistical powering.

HARMONi-7 is a Phase III clinical trial evaluating ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.

HARMONi-GI3 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with bevacizumab plus chemotherapy in patients with first-line unresectable metastatic CRC.

ILLUMINE is a Phase III study being conducted by GORTEC, a cooperative group dedicated to Head and Neck Oncology, in recurrent / metastatic head and neck squamous cell carcinoma (r/m HNSCC). ILLUMINE is a three-arm Phase III clinical trial designed to evaluate ivonescimab monotherapy, as well as ivonescimab in combination with ligufalimab, Akeso’s proprietary anti-CD47 monoclonal antibody, compared to monotherapy pembrolizumab in patients with PD-L1 positive r/m HNSCC.

In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials, HARMONi-A, HARMONi-2, and HARMONi-6, for ivonescimab in NSCLC, including a statistically significant overall survival benefit in both the HARMONi-A and HARMONi-6 studies, and a manageable safety profile in each study.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.

Akeso is actively conducting multiple Phase III clinical studies in settings outside of NSCLC, including biliary-tract cancer, triple-negative breast cancer, head and neck squamous cell carcinoma, small cell lung cancer, colorectal cancer, and pancreatic cancer.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024.

(Press release, Summit Therapeutics, MAY 31, 2026, View Source [SID1234666258])