On June 1, 2025 Taiho Oncology, Inc., and Cullinan Therapeutics, Inc., reported the publication of positive results from the REZILIENT1 trial in the peer-reviewed Journal of Clinical Oncology (JCO). REZILIENT1 is a Phase 1/2, global, multicenter study of zipalertinib (development code: CLN-081/TAS6417) in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) who have received prior therapy (Press release, Taiho, JUN 1, 2025, View Source [SID1234653566]). Results from the REZILIENT1 trial will be presented in a simultaneous oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #8503).

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The full publication, titled Zipalertinib in Patients With Epidermal Growth Factor Receptor Exon 20 Insertion-Positive Non-Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab, can be found here.

Highlights of the REZILIENT1 Phase 1/2 trial in the authors’ conclusions include:

Zipalertinib demonstrated clinically meaningful efficacy in the primary efficacy population (n=176), including 51 patients who had received prior amivantamab.
The confirmed objective response rate (ORR) was 35.2% overall, and median duration of response (mDOR) and progression-free survival were 8.8 months and 9.4 months, respectively.
In patients treated after prior platinum-based chemotherapy only (n=125), ORR was 40% with mDOR of 8.8 months.
The safety profile of zipalertinib was manageable and consistent with previously reported data.¹
In exploratory subgroup analyses:
Patients who had received prior amivantamab without other ex20ins-targeted therapy showed a confirmed ORR of 30% and mDOR of 14.7 months.
Patients with brain metastases showed a confirmed ORR of 30.9% and a mDOR of 8.3 months.
"Despite recent treatment advances for patients with EGFR ex20ins-mutant NSCLC, there is a lack of oral targeted therapies for patients whose tumors harbor these mutations," said principal investigator Zofia Piotrowska, MD, Assistant Professor, Medicine, Harvard Medical School and a clinical researcher and lung cancer medical oncologist at the Massachusetts General Hospital Cancer Center. "Findings from the Phase 1/2 REZILIENT1 trial support our understanding of zipalertinib as a potential targeted therapy option for patients living with previously treated recurrent or metastatic NSCLC harboring EGFR ex20ins mutations."

Taiho Oncology is actively recruiting patients in the Phase 3 REZILIENT3 trial (NCT05973773).

About REZILIENT1
REZILIENT1 (Researching Zipalertinib In EGFR Non-Small Cell Lung Cancer Tumors) is a Phase 1/2 clinical trial (NCT04036682) to evaluate efficacy and safety of zipalertinib in adult patients with advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations who have received prior therapy. The primary endpoints were ORR and DOR as assessed by blinded independent central review (ICR) per RECIST v1.1. Adverse events were characterized and graded according to Common Terminology Criteria for Adverse Events (CTCAE v5.0).

About Zipalertinib
Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with exon 20 insertion mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib has received Breakthrough Therapy Designation from the FDA. Zipalertinib is investigational and has not been approved by any health authority.

Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

About EGFR Exon 20 Insertion Mutations
NSCLC is a common form of lung cancer and up to 4% of all cases have EGFR exon 20 insertions, which makes them the third most common EGFR mutation subtype.2 In the United States, approximately 16% of patients with NSCLC harbor EGFR mutations,3 with insertions at exon 20 accounting for up to 12% of these mutations.

On June 1, 2025 Innovent Biologics, Inc (Suzhou) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported the data from Phase 1 and Phase 2 clinical studies of IBI363, first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein, for the treatment of "immune cold tumor" —immunotherapy-pretreated melanoma (acral and mucosal subtypes) were orally presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. IBI363 has shown breakthrough efficacy in patients with heavily-treated melanoma subtypes – which are traditionally treatment-resistant "cold" tumors, and a pivotal registration trial for IBI363 is currently ongoing (Press release, Innovent Biologics, JUN 1, 2025, View Source;bias-bispecific-antibody-fusion-protein-from-phase-1-and-2-clinical-studies-on-immunotherapy-treated-advanced-malignant–302470081.html [SID1234653565]).

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Innovent Biologics is conducting clinical studies in China, the United States, and Australia to explore the efficacy and safety of IBI363 for multiple tumor indications, including immune resistance, cold tumors, and front-line treatments. At this year’s ASCO (Free ASCO Whitepaper) meeting, IBI363 reported encouraging Phase 1/2 clinical data in the first three indications explored—non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and melanoma—focusing on IO-resistant and cold tumors. The data comprehensively demonstrated the breakthrough clinical outcomes of IBI363 across these indications, from robust tumor response to long-term survival benefits. These findings provide strong support of the drug’s novel mechanism of action translating effectively into clinical outcomes, and imply its potential for broader clinical development, offering new hope in areas of immunotherapy where treatment options remain limited.

A Phase 1/2 clinical study of PD-1/IL-2α-bias bispecific antibody fusion protein (IBI363) in the treatment of advanced "cold" tumor subtypes (acral and mucosal) malignant melanoma

The data presented at this ASCO (Free ASCO Whitepaper) meeting are from two multi-center Phase 1 and 2 clinical studies (registration no.: NCT05460767, NCT06081920) designed to evaluate the efficacy and safety of IBI363 monotherapy in the treatment of advanced melanoma. As of April 7, 2025, a total of 31 patients with unresectable, locally advanced or metastatic acral and mucosal melanoma who had previously received immunotherapy were enrolled and treated at the dosage of 1 mg/kg Q2W, and 64.5% of them had ≥2 lines of prior treatment.

Breakthrough efficacy of IBI363 monotherapy has been achieved in patients with "immune-cold" melanoma, with notable durable response and prolonged survival benefit:

In patients with at least one post-baseline tumor assessment (n=30), the confirmed objective response rate (cORR) was 23.3%, including 25.0% for mucosal type and 20.0% for acral type. The disease control rate (DCR) reached 76.7%, with 85.0% in mucosal type and 60.0% in acral type.
In patients treated with 1 mg/kg Q2W with confirmed responses (n=7), a durable response was observed with a median duration of response (DoR) of 14.0 months and events of 42.9%.
In patients treated with 1 mg/kg Q2W (n = 31) had a median progression-free survival (PFS) of 5.7 (2.7, 6.8) months, which was significantly longer than data from previous studies (PFS less than 3 months[1] ). The median follow-up time was 14.7 months, the median overall survival (OS) was 14.8 (9.9, NC) months, and the median OS of patients with mucosal subtype was 19.3 (9.9, NC) months. The overall 12-month OS rate was 61.5%.
In terms of safety, IBI363 was generally well tolerated. Among the subjects treated with 1 mg/kg Q2W (n = 31), the treatment-related adverse events (TRAEs) with an incidence > 30% were arthralgia, rash, and hyperthyroidism, most of which were Grade 1 or 2. The overall incidence of Grade ≥ 3 TRAEs was 29.0%, and only 3.2% of subjects discontinued treatment due to TRAEs. Overall safety was manageable, and no new safety risks were found.

Acral+Mucosal

(1mg/kg Q2W)

N=31

Confirmed ORR, % (95% CI)

23.3 (9.9, 42.3)

DCR, % (95% CI)

76.7 (57.7, 90.1)

Median PFS, months (95% CI)

5.7 (2.7, 6.8)

Median OS, months (95% CI)

14.8 (9.9, NC)

12-month OS rate, % (95% CI)

61.5 (39.8, 77.3)

Median OS follow-up, months

14.7

A pivotal Phase 2 registrational study of IBI363 in the treatment of advanced acral and mucosal malignant melanoma has been initiated

Innovent Biologics announced a trial in progress (TiP) . It is a randomized, open-label, multi-center Phase 2 study evaluating the efficacy and safety of IBI363 monotherapy compared to pembrolizumab (Keytruda) in patients with unresectable, locally advanced or metastatic mucosal and acral melanoma who have not received prior systemic treatment. As the first pivotal registration trial of IBI363, this study is designed to directly compare IBI363 monotherapy with pembrolizumab in this patient population. A total of 180 patients are planned to be enrolled and randomized in a 1:1 ratio. The primary endpoint is progression-free survival (PFS) assessed by an Independent Review Committee (IRC).

The first patient was dosed in March 2025, marking a significant step in advancing IBI363’s development in melanoma. Additional studies exploring IBI363 in combination therapies across other cancer types are also ongoing.

Professor Guo Jun from Peking University Cancer Hospital and the Principal Investigator of Melanoma Studies on IBI363 said: "Although melanoma is a relatively rare malignant tumor in China, it has a high mortality rate, and its incidence continues to rise each year. Historically, patients with melanoma who have not received immunotherapy have had a median PFS of only about 3 months, which highlights a significant unmet clinical need. Notably, non-cutaneous melanoma (especially mucosal melanoma) accounts for a large proportion of cases in China and is considered a ‘cold tumor’, typically unresponsive to traditional immunotherapy. In these cases, the response rate to PD-1 monotherapy is often below 15%, offering limited clinical benefit. More effective treatments are urgently needed[2]. IBI363 addresses this challenge by transforming ‘cold tumors’ into ‘hot tumors’ through dual activation of the PD-1 and IL-2 pathways. The data presented in this study showed that IBI363 delivers significantly improved efficacy compared to previous studies in cold tumor subtypes and standard of care therapies, while maintaining a favorable safety profile. IBI363 has the potential to become a new standard in immunotherapy for malignant melanoma in China, providing a long-needed treatment option for patients with acral and mucosal malignant melanoma."

Dr. Zhou Hui, Senior Vice President of Innovent Biologics, said: "At present, there is a huge unmet clinical need for the treatment of unresectable, locally advanced or metastatic mucosal and acral melanoma in China. Approved PD-1 therapies have not substantially improved first-line outcomes in melanoma, and the clinical benefits remain limited[3]. IBI363 is leading the evolution of next-generation immunotherapy. By leveraging a dual-mechanism of ‘PD-1 blockade + IL-2 directed activation’, IBI363 enhances T cell function and expands T cell populations to reshape the tumor immune microenvironment. IBI363 has shown excellent efficacy and safety results in the treatment of patients with immune-cold melanoma subtypes. A Phase 2 pivotal registrational study is currently underway. Positive results in patients with mucosal and acral melanoma are highly anticipated, offering hope for a more effective treatment option. Meanwhile, we are accelerating the global development of IBI363 across multiple tumor types, with the goal of making this innovative treatment accessible to patients around the world."

About Melanoma

Melanoma is a malignant tumor that develops from melanocytes. While it accounts for only 3% of all skin cancers, it has the highest mortality rate and is the most prone to metastasis. In China, both the incidence and mortality rates of melanoma are rising annually. Based on tumor location, melanoma is classified into cutaneous, acral, and mucosal subtypes. Melanoma in Chinese populations differs significantly from that in Caucasian populations in Europe and the United States with regard to pathogenesis, biological behavior, histological morphology, treatment methods, and prognosis[4]. For patients with advanced cutaneous and acral melanoma with BRAF V600 mutation, a combination of BRAF and MEK inhibitors is the preferred treatment. For those without this mutation, chemotherapy combined with anti-angiogenic drugs is often considered as first-line treatment. Although pembrolizumab was approved in Sep. 2024 for first-line treatment of melanoma, the clinical benefit of PD-1 inhibitors in this setting remains modest. In second-line treatment, agents different from those used in the first line are generally preferred. For patients not previously treated with a PD-1 inhibitor, it can be considered as a second-line option. In advanced mucosal melanoma, median PFS for patients without prior immunotherapy is only about 3 months. Given the limited efficacy of current treatments for non-cutaneous melanomas, especially mucosal subtypes, which are more prevalent in China, there is an urgent need for more effective therapies.

About IBI363 (PD-1/IL-2 α-bias bispecific antibody fusion protein)

IBI363 is the world’s first PD-1/IL-2α-bias bispecific fusion protein independently developed by Innovent Biologics. It integrates two key functions: blockade of the PD-1/PD-L1 pathway and activation of the IL-2 signaling pathway. The IL-2 arm of IBI363 has been engineered to retain affinity for IL-2 Rα while reducing binding to IL-2Rβ and IL-2Rγ, thereby minimizing toxicity. The PD-1 binding arm enables simultaneous PD-1 blockage and selective delivery of IL-2. This differential targeting strategy exploits the fact that newly activated tumor-specific T cells co-express PD-1 and IL-2α, which allows for more precise and efficient targeting and activation of this T cell subset. IBI363 not only showed good anti-tumor activity in a variety of tumor-bearing pharmacological models but also showed prominent anti-tumor efficacy in PD-1 resistance and metastasis models.

Driven by urgent clinical needs, Innovent Biologics is conducting clinical studies in China, the United States, and Australia to assess the efficacy and safety of IBI363 across multiple tumor types. The first pivotal registration trial of IBI363 has been initiated for the treatment of mucosal and acral melanoma without immunotherapy.

IBI363 has been granted two fast track designations by the FDA for the treatment of advanced squamous non-small cell lung cancer and melanoma, respectively. IBI363 has also been granted Two Breakthrough Therapy Designations by the National Medical Products Administration (NMPA) for the treatment of advanced melanoma and squamous NSCLC.

On June 1, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major diseases, reported that the clinical data of IBI363 (first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein) monotherapy and combo-therapy with bevacizumab in advanced colorectal cancer were orally presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Innovent Biologics, JUN 1, 2025, View Source [SID1234653564]). IBI363 demonstrated encouraging response and overall survival benefit in the context of colorectal cancer, which is typically considered an immunologically ‘cold’ tumor, supports its unique mechanism of actions (MoA) of turning "cold tumor" into "hot tumor".

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Innovent Biologics is conducting clinical studies in China, the United States, and Australia to explore the efficacy and safety of IBI363 for multiple tumor indications, including immune resistance, cold tumors, and front-line treatments. At this year’s ASCO (Free ASCO Whitepaper) meeting, IBI363 reported encouraging Phase 1/2 clinical data in the first three indications explored—non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and melanoma—focusing on IO-resistant and cold tumors. The data comprehensively demonstrated the breakthrough clinical outcomes of IBI363 across these indications, from robust tumor response to long-term survival benefits. These findings provide strong support of the drug’s novel mechanism of action translating effectively into clinical outcomes, and imply its potential for broader clinical development, offering new hope in areas of immunotherapy where treatment options remain limited.

PD-1/IL-2α-bias bispecific antibody fusion protein IBI363 monotherapy and combined with bevacizumab in participants with advanced colorectal cancer: results from Phase 1 studies

Two Phase 1 studies (NCT05460767, NCT06717880) were conducted to evaluate the safety, tolerability and preliminary efficacy of IBI363 monotherapy and combined with bevacizumab in patients with advanced colorectal cancer.

IBI363 monotherapy has demonstrated breakthrough antitumor therapeutic potential, showing a significant extension of overall survival compared to data of standard-of-care therapies

As of the data cutoff date (Apr 7th, 2025), a total of 68 participants with advanced colorectal cancer received IBI363 monotherapy at the dose levels from 0.1 mg/kg to 3mg/kg. No patients were confirmed as microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR). 86.8% of patients were microsatellite stable (MSS) or proficient mismatch repair (pMMR). 61.8% of patients had liver metastases. 63.2% of patients had previously received 3 or more lines of systemic anti-tumor treatments. 23.9% of patients had received prior immunotherapy.
Notably, among patients receiving monotherapy with IBI363 (n=68), with a median follow-up time of 20.1 months, the median overall survival (OS) reached 16.1 months, demonstrating a significant improvement compared to the historical data of standard treatments (ranging from 6.4 to 9.3 months1-3).
Subgroup analyses revealed that patients with or without liver metastasis both showed excellent overall survival (OS), indicating significant clinical benefit. The median OS were 14.4 months (with liver metastasis) and 17.0 months (without liver metastasis).
Among patients treated with monotherapy of IBI363 1 mg/kg every 2 weeks (Q2W) (n=22), the confirmed objective response rate (cORR) was 13.6%.

Liver metastasis
(n = 42)

without liver metastasis
(n = 26)

Total

(n = 68)

Median OS, month (95% CI)

14.4 (8.0, 18.8)

17.0 (9.9, NC)

16.1 (10.1, 18.8)

6-month OS rate, % (95% CI)

81.3 (64.6, 90.6)

80.0 (58.4, 91.1)

80.7 (68.5, 88.6)

12-month OS rate, % (95% CI)

54.8 (36.9, 69.5)

59.5 (37.8, 75.8)

56.6 (43.0, 68.1)

18-month OS rate, % (95% CI)

37.6 (21.3, 53.9)

44.8 (24.0, 63.6)

40.3 (27.2, 53.0)

OS median follow-up time, month (95% CI)

20.2 (17.9, 20.7)

20.1 (16.8, 21.7)

20.1 (17.7, 20.6)

The combination of IBI363 and bevacizumab demonstrated encouraging efficacy signals and a manageable safety profile, with excellent data on objective response rate and progression-free survival

As of the data cutoff date (Apr 7th, 2025), a total of 73 patients with advanced colorectal cancer received IBI363 （dose levels from 0.6 mg/kg to 3mg/kg） and bevacizumab combination therapy. No patients were confirmed as MSI-H or dMMR. 91.8% of patients were MSS or pMMR. 56.2% of patients had liver metastases. 54.8% of patients had previously received 3 or more lines of systemic anti-tumor treatments. 16.4% of patients had received prior immunotherapy.
In all participants treated with IBI363 in combination with bevacizumab (n=73), the cORR was 15.1% and the disease control rate (DCR) was 61.6%. With a median follow-up time of 9.9 months, the median progression free survival (PFS) reached 4.7 months. With a median follow-up time of 9.4 months, OS was not mature, with events in only 13 participants (17.8%).
As for the combination therapy in patients without liver metastases (n=32), the confirmed ORR was 31.3%, with a DCR of 81.3%. The median PFS reached to 7.4 months.
In those participants who received IBI363 at 3 mg/kg Q3W plus bevacizumab (n=31), confirmed ORR and DCR increased to 19.4% and 71.0%, respectively. The median PFS increased to 5.6 months.

IBI363 3 mg/kg Q3W +Bevacizumab

(n = 31)

Without liver metastasis
(n = 32）

Total

(n = 73)

Confirmed ORR, % (95% CI)

19.4 (7.5, 37.5)

31.3 (16.1, 50.0)

15.1 (7.8, 25.4)

DCR, % (95% CI)

71.0 (52.0, 85.8)

81.3 (63.6, 92.8)

61.6 (49.5, 72.8)

Median PFS, month (95% CI)

5.6 (2.5,6.8)

7.4 (4.1, 9.8)

4.7 (2.5,6.7)

PFS median follow-up time, month (95% CI)

8.6 (7.2, 10.2)

9.9 (7.2, 13.1)

9.9 (7.2, 13.9)

In terms of safety, among participants receiving monotherapy and combination therapy, 19 (27.9%) and 26 (35.6%) reported treatment-related adverse events (TRAEs) of Grade 3 or higher, respectively. The most common TRAEs were arthralgia, anemia, rash, and hypothyroidism. No new safety signals were observed, with a manageable risk-benefit profile in IBI363 alone or in combination with bevacizumab.
Tumor immune cell infiltration analysis supports the IBI363 MOA of turning "cold tumor" into "hot tumor", demonstrating enrichment of PD1+CD25+CD8+ cells in baseline tumor tissue association with clinical efficacy

In baseline tumor tissues, elevated infiltration of CD8+ cells, CD25+CD8+ cells, and PD1+CD25+CD8+ cells were associated with improved clinical response to IBI363 monotherapy (partial response or stable disease). This supports the potential anti-tumor effects of IBI363 in the treatment of colorectal cancer from the perspective of its mechanism of action.
Professor Tao Zhang, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, stated: "Colorectal cancer is the third most common cancer type globally and ranks fourth in cancer-related mortality4. About 86% of colorectal cancer are in an immune ‘desert’ or immune-inflamed suppressed state, rendering traditional immune checkpoint inhibitors (ICIs) ineffective5. For colorectal cancer that has failed standard treatments, there are limited therapeutic options with short survival periods, representing a significant unmet clinical need6. IBI363, as a PD-1/IL-2α-bias bispecific fusion protein, has demonstrated robust antitumor efficacy in preclinical studies through the effective expansion of tumor-specific CD8⁺ T cells (TST cells). Its ability to block PD-1 and stimulate TST cells holds the potential to transform ‘cold’ tumors into ‘hot’ tumors. As a monotherapy, IBI363 achieves a median survival of 16.1 months in later-line treatments, which represents a significant improvement compared to the median survival of current standard therapies and also confirms its potential with a strong ‘tail effect’ as a PD1 plus cytokine bispecific immunotherapy. The combination of IBI363 with bevacizumab is still under continuous follow-up, having shown promising efficacy and tolerable safety, with unique efficacy characteristics particularly in the subgroup without liver metastasis. Overall, clinical data suggest that IBI363 combined with bevacizumab holds significant promise for colorectal cancer and warrants further exploration."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "On top of the preliminary data reported at 2024 ASCO (Free ASCO Whitepaper) and 2024 ESMO (Free ESMO Whitepaper), we are presenting more updated follow-up data and combination therapy results of IBI363 at the ASCO (Free ASCO Whitepaper) Congress this year. From a comprehensive body of clinical evidence that includes ORR, PFS, OS, IBI363 demonstrated robust antitumor activity of both monotherapy and combination therapy in patients with advanced colorectal cancer who are non-MSI-H/dMMR. We are eyeing on long-term survival data from high dose in longer follow-up period. And the pivotal study of IBI363 targeting advanced CRC is in plan. Observing such results in the context of colorectal cancer, which is typically considered an immunologically ‘cold’ tumor, further highlights the broad development potential of IBI363. It offers hope for expanding into areas where immunotherapy has been less effective or even unresponsive."

About IBI363 (First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein)

IBI363 is a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein independently developed by Innovent Biologics. It functions by both blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway. The IL-2 arm of IBI363 is designed to maintain its affinity for IL-2Rα while reducing binding to IL-2Rβ and IL-2Rγ, thereby minimizing toxicity. The PD-1 binding arm not only blocks PD-1 but also selectively delivers IL-2. This approach targets and activates tumor-specific T cells that express both PD-1 and IL-2α, leading to more precise and effective activation of this T cell subpopulation. IBI363 has demonstrated robust antitumor activity in various tumor-bearing pharmacological models, but also showed outstanding efficacy in PD-1 resistance and metastasis models.

In response to urgent clinical needs, Innovent is conducting clinical studies in China, the United States and Australia to further explore the efficacy and safety of IBI363 in various tumor indications, including immune-resistant, cold tumors, and front-line treatments. The first pivotal trial of IBI363 was initiated in 2025 for unresectable locally advanced or metastatic mucosal or acral melanoma who have not received prior systemic therapy.

IBI363 has received two fast track designations (FTD) from the U.S. FDA and two breakthrough designations (BTD) from the China NMPA, for the treatment of squamous non-small cell lung cancer and melanoma, respectively.

On June 1, 2025 J INTS BIO, a company specializing in the development of therapeutics for cancer and rare diseases, reported interim results from the global Phase 1/2 clinical trial of JIN-A02, its fourth-generation EGFR-TKI drug candidate, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 (ASCO 2025), the world’s largest oncology conference, held in Chicago, USA (Press release, J INTS BIO, JUN 1, 2025, View Source [SID1234653563]).

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JIN-A02 is an oral, fourth-generation EGFR-TKI designed to overcome resistance mutations (such as C797S) that develop after treatment failure with third-generation EGFR-TKIs, which are currently the first-line therapy for EGFR-mutant Non-small cell lung cancer (NSCLC). It is currently undergoing clinical trials in South Korea, the United States, Thailand, and other countries. Key efficacy and safety results from Part A (dose escalation) of the multi-center clinical trial (NCT05394831) were presented.

‘Confirmed’ clinical response observed in patients with disease progression after 3rd Generation EGFR TKI and chemotherapy

One of the key findings of the ASCO (Free ASCO Whitepaper) presentation was that tumor responses were sustained in specific dose cohorts, with confirmed partial responses (PRs) verified by independent evaluation. Confirmed PRs were observed in 50mg,100mg and 300mg QD dose groups, providing clinical evidence of anti-tumor activity.

In the 50 mg dose group, patients achieved a 77.3% reduction in tumor size, maintaining a PR over six consecutive treatment cycles (from cycle 3 to cycle 13). In the 300 mg dose group, a confirmed PR was observed with a 39.7% tumor size reduction, including a significant reduction in brain metastatic lesions. In the 100 mg dose group, a PR was also reported with a 35.3% reduction in tumor size, and brain metastatic lesions remained stable, further supporting the potential of JIN-A02 in treating brain metastases.

Safety confirmed up to 300 mg, with therapeutic signals in brain metastases

No dose-limiting toxicities (DLTs) or serious adverse events were observed with JIN-A02 at doses up to 300mg, which is six times the dose level when PR was first observed, demonstrating a favorable safety profile even at higher dose levels. The majority of adverse events reported at 300mg were mild (Grade 1-2) and included for the first time, Grade 1 skin rash, diarrhea, and skin desquamation in 3 out of 5 subjects – events commonly associated with EGFR inhibitors and generally considered clinically manageable. Importantly, there were no reports of systemic toxicities such as cardiovascular events or hepatotoxicity, supporting the drug’s excellent safety profile. This safety and tolerability have translated into extended treatment durations in real-world settings, with a patient still on JIN-A02 after one year and seven months.

In addition, the trial demonstrated notable responses in brain metastases first noted at 100mg, suggesting that JIN-A02 achieves therapeutically relevant concentrations in brain tissue.

JIN-A02 gains national spotlight as government grants accelerate development

In addition to the ASCO (Free ASCO Whitepaper) announcement, J INTS BIO continues to achieve noteworthy results in Korea. Recently, it was selected for the ‘2025 Baby Unicorn Fostering Project’ by the Ministry of SMEs and Startups, officially recognizing both our scientific technology and commercialization potential. The ‘Baby Unicorn Fostering Project’ is a government project that focuses on developing promising startups with innovative technologies and growth potential in the global market as ‘potential unicorns’. Companies selected for this project will receive full government support in recognition of their technological prowess and growth potential.

With these accolades, JIN-A02 will receive dual funding for its Phase 2 trial and global expansion over the next two years, which is expected to be a decisive point to significantly accelerate the pace of clinical and commercialization in parallel with private investment. It is also significant as a case of securing confidence in the 3 arena of technology, marketability, and global scalability, as the recognition came from different government departments.

Based on these achievements, we plan to initiate the Phase 2 clinical trial of JIN-A02 in before the end of this year, in discussions with the US FDA.

"The ASCO (Free ASCO Whitepaper) presentation of JIN-A02’s ability to induce anti-cancer responses and its ability to respond to central nervous system metastatic lesions is of great significance," said Dr. Anna Jo, CEO. "The government’s continued support is a recognition of our technical capabilities and potential for growth. We will take advantage of this opportunity to accelerate global clinical expansion, technology transfer, and indication expansion to realize our goal of early commercialization"

On June 2, 2025 Imugene Limited (ASX: IMU), a clinical-stage immuno-oncology company, reported the first site activation within Australia, as part of the investigator sponsored Phase II Neo-POLEM clinical trial (Press release, Imugene, JUN 2, 2025, https://mcusercontent.com/e38c43331936a9627acb6427c/files/0af44840-0a27-5641-dade-e0642353307d/1st_Australian_site_activated_PD1_Vaxx_Neo_POLEM_Ph_II_trial.pdf [SID1234653561]).

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Neo-POLEM is a Phase II study investigating the potential of PD1-Vaxx, a neoadjuvant PD-1 vaccine, to improve treatment outcomes for patients with mismatch repair-deficient / microsatellite instability high (dMMR/MSI-high) colorectal cancer. Approximately 15% of patients with colorectal cancer have the dMMR/MSI-high subtype.

The trial is an IST being conducted by Cancer Research UK Southampton Clinical Trials Unit in collaboration with Royal Surrey Hospital NHS Foundation Trust and the Australasian Gastro-Intestinal Trial Group (AGITG).

The primary objective of the study is to determine major pathological response rates, a measure of tumour size reduction post-treatment with PD1-Vaxx before surgery, with secondary objectives to assess the safety of PD1-Vaxx, evaluate biomarkers, and evaluate the objective response rates and overall survival.

This trial builds upon compelling early evidence that immunotherapy can deliver significant benefits in this patient population. The trial will recruit patients in both Australia and the United Kingdom.

Imugene’s CEO and Managing Director Leslie Chong said: "We’re very pleased to see this Neo-POLEM IST open and enrolling in Australia. PD1-Vaxx has the potential to offer a durable immune response and improve treatment outcomes, and we look forward to further progress in both Australia and the UK."

Colorectal cancer (CRC), also known as bowel cancer, is the third most common cancer, with a worldwide annual incidence of more than 1.2 million cases and a mortality rate of approximately 50%. About 80% of patients with colon cancer have localised and resectable disease at diagnosis. Approximately 15% of CRC is dMMR/MSI-high.