Innovent Delivers Oral Presentation on Phase 1 Clinical Data of IBI363 (First-in-class PD-1/IL-2α-bias Bispecific Antibody Fusion Protein) in Advanced Non-small Cell Lung Cancer at the 2024 WCLC

Rhea-AI Summary

Innovent Biologics presented Phase 1 clinical data for IBI363, a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein, in advanced non-small cell lung cancer (NSCLC) at the 2024 World Conference on Lung Cancer. The study enrolled 134 patients, with 95.5% having received prior PD-(L)1 immunotherapy. Key findings include:

- Overall ORR of 20.8% and DCR of 74.4% in 125 evaluable patients
- In squamous NSCLC, 3 mg/kg Q3W dosing showed ORR of 34.5% and DCR of 89.7%
- Efficacy observed regardless of PD-L1 expression
- Manageable safety profile with 20.1% experiencing grade ≥3 TRAEs

IBI363 demonstrates promising antitumor activity in IO-resistant NSCLC, potentially offering a new treatment option for patients with alternatives.

Positive

• Overall ORR of 20.8% and DCR of 74.4% in 125 evaluable patients
• In squamous NSCLC, 3 mg/kg Q3W dosing showed ORR of 34.5% and DCR of 89.7%
• Efficacy observed regardless of PD-L1 expression levels
• Manageable safety profile with 20.1% experiencing grade ≥3 TRAEs
• Median PFS of 5.5 months for 1/1.5 mg/kg group in squamous NSCLC
• 12-month PFS rate of 30.7% in 1/1.5 mg/kg group, indicating long-term benefit

Negative

• 6.0% of patients experienced TRAEs leading to treatment discontinuation
• Median PFS not yet reached for 3mg/kg Q3W group, indicating immature data
• Relatively short follow-up time for the 3mg/kg Q3W subgroup

SAN FRANCISCO and SUZHOU, China, Sept. 10, 2024 /PRNewswire/ -- 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, announced the presentation of Phase 1 clinical data (ClinicalTrials.gov, NCT04085185) for IBI363 (first-in-class PD-1/IL-2^α-bias bispecific antibody fusion protein) in advanced non-small cell lung cancer at the 2024 World Conference on Lung Cancer (WCLC). Currently, Innovent is conducting Phase 1/2 clinical trials in China, U.S. and Australia to evaluate the safety, tolerability and efficacy of IBI363 in subjects with advanced solid tumors.

First-in-class PD-1/IL-2^α-bias bispecific antibody IBI363 in patients with advanced non-small cell lung cancer in a Phase 1 study

• This update on previously reported Phase 1 results focuses on the safety and efficacy of IBI363 in advanced non-small cell lung cancer (NSCLC). As of the follow-up data cutoff date of August 2, 2024, 134 patients were enrolled and received IBI363 monotherapy (up to 3 mg/kg Q3W), with 95.5% having received prior PD-(L)1 immunotherapy. The median duration of IBI363 exposure was 10 weeks, and 77.6% remained on treatment. In the group of 125 patients having at least one post-baseline tumor assessment, the overall ORR was 20.8% and DCR was 74.4%.
• IBI363 demonstrated encouraging efficacy signals in IO-treated squamous NSCLC, with a trend toward relatively higher ORR and DCR in the 3 mg/kg Q3W group (n=29）compared to the 1/1.5 mg/kg Q2W/Q3W group (n=27) (see table below). Despite relatively short follow-up time for the 3mg/kg Q3W subgroup, among the 18 patients who had at least 12 weeks of follow-up or end of study, the ORR and DCR were 50% and 88.9%, respectively.

Patients with at least 1 tumor assessment	sqNSCLC
	1/1.5 mg/kg (N=27)	3 mg/kg (N=29)	3 mg/kg with at least 12 weeks of follow-up (N=18)
Best overall response, n (%)
Partial Response (PR)	6*	10**	9***
Stable Disease (SD)	13	16	7
Progressive Disease (PD)	8	2	2
Not Evaluable (NE)	0	1	0
ORR, % (95% CI)	22.2% (8.6, 42.3)	34.5% (17.9, 54.3)	50.0% (26.0, 74.0)
DCR, % (95% CI)	70.4% (49.8, 86.2)	89.7% (72.6, 97.8)	88.9% (65.3, 98.6)

^*6 patients had confirmed PR; ^**9 out 10 patients had confirmed PR; ^***8 of 9 patients had confirmed PR.

• As of the data cutoff date, for patients with squamous NSCLC who were treated with IBI363 at 1/1.5 mg/kg, the median follow up time was 7.5 months, and the median PFS was 5.5 months (95% CI, 1.5-8.3); currently, the 12-month PFS rate is 30.7%, showing a long-term benefit advantage of immunotherapy. The median PFS was not reached for subjects who received 3mg/kg Q3W.
• Similar responses were observed among squamous NSCLC patients with PD-L1 TPS<1% (n=22) and TPS≥1% (n=22) treated across the 1/1.5 mg/kg and 3 mg/kg doses, with ORRs of 36.4% and 31.8% respectively, suggesting IBI363 has efficacy regardless of PD-L1 expression.
• IBI363 has a manageable safety profile. The most common treatment related adverse events (TRAEs) included arthralgia, anemia, hyperthyroidism, hypothyroidism and rash. Overall, 20.1% of patients experienced TRAEs ≥ grade 3 and 6.0% experienced TRAE leading to treatment discontinuation. In the 3 mg/kg Q3W subgroup (n=57), 17.5% experienced TRAEs ≥ grade 3 and 5.3% experienced TRAEs leading to treatment discontinuation. The safety profile was consistent with the overall population. No new safety signals were identified.

Given that IBI363 has shown encouraging efficacy signals and good tolerability, this study continues to investigate the long-term efficacy and safety and to determine the RP2D in NSCLC. Additional studies are also underway to evaluate IBI363 in combination with other therapies and in other solid tumors. Relevant data and analyses will be shared in future academic conferences or publications.

Professor Jianya Zhou, The First Affiliated Hospital, School of Medicine, Zhejiang University, stated: "Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer accounting for approximately 80% of cases^[1]. While PD-1/PD-L1 inhibitors have shown promising efficacy in non-small cell lung cancer, most patients eventually develop primary or secondary resistance to these immune checkpoint inhibitors. For NSCLC patients who fail IO therapy, effective treatment options are limited, with chemotherapy, such as docetaxel, achieving only about an ORR of 10% and a median PFS of under 4 months^[2]. As a key cytokine that activates tumor-specific CD8+T cells, IL-2 complements immune checkpoint inhibitors in its MOA. Combining PD-1 with IL-2 may reverse the exhaustion of tumor-specific CD8+ T cells and help overcome immune resistance. As a PD-1/IL-2^α-bias bispecific molecule, IBI363 has demonstrated promising antitumor activity in IO-resistant, driver gene wild-type NSCLC, with clinical benefits shown in both ORR and PFS. Additionally, its manageable safety profile, even at higher doses, provides confidence in its therapeutic potential."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to present the latest data on IBI363 in lung cancer at WCLC. The data highlights the promising trend of IBI363 showing better ORR and DCR at higher doses, alongside a manageable safety profile. Although the follow-up period for the 3 mg/kg dose group is still relatively short, we anticipate more mature data from longer-term follow-up and expect to see its potential as an immunotherapy for long-term survival benefits to patients. Meanwhile, in non-small cell lung cancer, particularly in IO-treated squamous NSCLC, IBI363 has demonstrated potent anti-tumor effects regardless of PD-L1 expression levels. This indicates that IBI363 could potentially offer breakthroughs in treating cold tumors with low or absent PD-L1 expression. We will continue to advance the clinical exploration of IBI363 in squamous NSCLC and other tumor types."

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

IBI363 is a first-in-class PD-1/IL-2^α-bias bispecific antibody fusion protein developed independently 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-2Rα, leading to more precise and effective activation of this T cell subpopulation. IBI363 has demonstrated robust antitumor activity in various tumor-bearing pharmacological models, including those resistant to PD-1 resistance and models of metastasis. 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 advanced tumors.

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 11 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.

References [1] Sung H, Ferlay J, Siegel R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: a cancer journal for clinicians, 2021, 71(3): 209-249. [2] TROPION-Lung01 ESMO 2023

 

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SOURCE Innovent Biologics

FAQ

What is the ORR of IBI363 in advanced NSCLC patients previously treated with PD-(L)1 immunotherapy?

In the study, IBI363 demonstrated an overall ORR of 20.8% in 125 evaluable patients with advanced NSCLC, 95.5% of whom had received prior PD-(L)1 immunotherapy.

How effective is IBI363 in squamous NSCLC patients at the 3 mg/kg Q3W dose?

For squamous NSCLC patients receiving IBI363 at 3 mg/kg Q3W, the ORR was 34.5% and DCR was 89.7%. In patients with at least 12 weeks of follow-up, the ORR increased to 50% and DCR to 88.9%.

Does PD-L1 expression affect the efficacy of IBI363 in NSCLC patients?

IBI363 showed similar responses in squamous NSCLC patients regardless of PD-L1 expression. Patients with PD-L1 TPS<1% and TPS≥1% had ORRs of 36.4% and 31.8% respectively, suggesting efficacy independent of PD-L1 levels.

What is the safety profile of IBI363 in the Phase 1 NSCLC study?

IBI363 demonstrated a manageable safety profile. 20.1% of patients experienced grade ≥3 treatment-related adverse events (TRAEs), and 6.0% had TRAEs leading to treatment discontinuation. Common TRAEs included arthralgia, anemia, hyperthyroidism, hypothyroidism, and rash.

What is the median progression-free survival (PFS) for IBI363 in squamous NSCLC patients?

For squamous NSCLC patients treated with IBI363 at 1/1.5 mg/kg, the median PFS was 5.5 months (95% CI, 1.5-8.3) with a 12-month PFS rate of 30.7%. The median PFS for the 3mg/kg Q3W group was not reached at the time of data cutoff.