On June 2, 2024 Flamingo Therapeutics ("Flamingo") reported the presentation of a Trial-in-Progress poster at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO 2024) taking place in Chicago, Illinois (Press release, Flamingo Therapeutics, JUN 2, 2024, View Source;utm_medium=rss&utm_campaign=flamingo-therapeutics-presents-poster-at-asco-2024-on-phase-ii-pemda-hn-trial-for-head-and-neck-squamous-cell-carcinoma-hnscc [SID1234643925]).

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Flamingo’s lead oncology program, danvatirsen, is an oligonucleotide discovered by Ionis that selectively targets STAT3 and has shown clinical activity in HNSCC. PEMDA-HN (NCT05814666) is a multicenter, open-label, randomized study evaluating the efficacy and safety of danvatirsen in combination with pembrolizumab compared with pembrolizumab alone as first-line treatment of patients with recurrent/metastatic HNSCC whose tumor expresses PD-L1. Two-thirds of patients will be randomized to receive danvatirsen and pembrolizumab and one-third will be randomized to receive pembrolizumab alone. The primary endpoint of the study is overall response rate by RECIST 1.1 as assessed by the investigator. The secondary endpoints include safety, duration of response, disease control rate, progression free survival and overall survival. PEMDA-HN is being conducted at study centers in the United States, South Korea and the United Kingdom.

ASCO poster details are as follows:

Abstract#: TPS6113
Title: "PEMDA-HN, an open-label, phase II, randomized controlled study of danvatirsen plus pembrolizumab compared to pembrolizumab alone in first-line recurrent and/or metastatic head and neck squamous cell carcinoma (RM HNSCC)"
Session Title: Poster Session – Head and Neck Cancer
Session Date and Time: June 2, 2024, 9:00am CDT
Presenting Author: Marshall R. Posner, MD, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai

For more information, please visit the ASCO (Free ASCO Whitepaper) 2024 website.

On June 2, 2024 Innovent Biologics, Inc. ("Innovent") (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 two oral presentations of its first-in-class anti-CLDN18.2/CD3 bispecific antibody (R&D code: IBI389) for the treatment of advanced pancreatic cancer (PDAC) and gastric or gastroesophageal tumors (G/GEJC) at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from clinical data of a Phase I study (NCT05164458) (Press release, Innovent Biologics, JUN 2, 2024, View Source [SID1234643942]).

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Dr. Hui Zhou, Senior Vice President of Innovent Biologics, stated, "We are excited to share the latest clinical development progress of IBI389 at ASCO (Free ASCO Whitepaper). Different from monoclonal antibodies, IBI389 redirects T cells to tumor cells by binding both CLDN18.2 expressed on tumor cells and CD3 on T cells, inducing T cell-mediated cell killing. Preclinical results showed that IBI389 could bind to tumor cells and exhibit significant anti-tumor effects even in cell lines with low CLDN18.2 expression. In the presented clinical data, IBI389 has shown promising efficacy in advanced G/GEJ tumors and PDAC, including those subjects with low and moderate CLDN18.2 expression. Notably, IBI389 is the world’s first bispecific antibody targeting CLDN18.2/CD3 to show encouraging efficacy signal in PDAC, representing a breakthrough for innovative treatments in difficult-to-treat cancers. We will continue to advance the clinical development of IBI389 for the benefit of more cancer patients."

Safety and Efficacy of IBI389 in Patients with Advanced Pancreatic Ductal Adenocarcinoma: Preliminary Results from the Phase I Study

Abstract#: 4011

As of March 11, 2024, a total of 72 subjects with advanced unresectable or metastatic pancreatic ductal adenocarcinoma have received IBI389 monotherapy. All subjects had received at least one prior systemic treatment, and 55.6% of the subjects had received two or more prior lines of systemic therapy.

The results showed that:

In subjects with CLDN18.2 IHC 2/3+≥10%, signs of efficacy were observed when treated with 100 μg/kg.
The recommended phase 2 dose (RP2D) 600 μg/kg group shows superior efficacy. 27 subjects have performed at least one post-baseline tumor evaluation, the objective response rate (ORR) was 29.6% (95%CI: 13.8-50.2), the confirmed objective response rate (cORR) was 25.9% (95%CI：11.1-46.3), and the disease control rate (DCR) was 70.4% (95%CI：49.8-86.2). Among the 18 subjects with CLDN18.2 IHC 2/3+≥40%, the cORR was 38.9% (95%CI：17.3-64.3).
As of May 1, 2024, the median progression-free survival (PFS) follow-up time was 4 months, and the median PFS was not yet mature, with a 3-month PFS rate of 57.1%.
Safety was similar to that of the overall population, and no new safety signals were observed.
Professor Jihui Hao, Tianjin Medical University Cancer Institute & Hospital, said, "Pancreatic cancer is one of the most aggressive malignancies with poor prognosis, and the incidence continues to increase. Currently, the standard treatment for most patients with metastatic pancreatic cancer is systemic chemotherapy. In the second-line treatment, the clinical options are very limited and primarily involving a different chemotherapy from the first-line regimen. The response rate to second-line chemotherapy is only 6%~16%, and the median survival time is only about 3~6 months [1,2]. Therefore, there is a great unmet clinical need for patients who have failed standard treatment. Studies have shown that the expression of CLDN18.2 in pancreatic cancer patients is up to 50%~70% [3], making it a potential novel target for therapy. IBI389 is the first bispecific antibody targeting CLDN18.2/CD3 that reported clinical data, and showed positive efficacy signals in patients with advanced pancreatic cancer. I hope the clinical exploration of this innovative drug could drive the progress in pancreatic cancer treatment."

Safety and Preliminary Efficacy Outcomes of IBI389 in Patients with Advanced Solid Tumors and Gastric or Gastroesophageal Tumors: A Phase I Dose Escalation and Expansion Study

Abstract#: 2519

This Phase I study is designed to evaluate the safety, tolerability, and preliminary efficacy of IBI389 in subjects with advanced solid tumors and G/GEJ tumors.

The results showed that:

As of May 1, 2024, 26 G/GEJC subjects with CLDN18.2 IHC 2/3+≥10% received ≥ 10 μg /kg IBI389 monotherapy and performed at least one post-baseline tumor evaluation, of which 8 subjects achieved partial response (PR); the objective response rate (ORR) and disease control rate (DCR) were 30.8% and 73.1%, respectively.
In terms of safety, as of March 11, 2024, a total of 120 subjects with advanced solid tumor malignancies who had previously failed or were intolerant to standard therapy were enrolled. IBI389 was generally well tolerated, and no dose-limiting toxicity (DLT) events were observed in each dose group. Cytokine release syndrome (CRS) occurred in 60% of subjects, and only one case developed grade 3. No grade 4 or 5 CRS happened. 58.3% subjects occurred ≥ grade 3 treatment-related adverse events (TRAEs). The most common ≥ grade 3 TRAEs were increased gamma-glutamyl transferase (21.7%), decreased lymphocyte count (13.3%) and decreased appetite (5. 0%）.
Professor Feng Bi, West China Hospital of Sichuan University, said, "Gastric cancer is one of the most common malignant tumors in the world, ranking the 5th most common malignant tumors, and the 4th leading cause of cancer death worldwide [4]. Single-agent chemotherapy is the main second-line treatment for advanced gastric cancer. Multiple studies have shown that the PFS of second-line single-agent chemotherapy is 2.0~4.1 months, and the OS was only 5.3~9.5 months, with limited clinical benefit [5]. In recent years, CLDN18.2 has gained the most attention as a therapeutic target in the field of gastrointestinal tumors, and studies have shown that the expression rate of CLDN18.2 in gastric cancer patients is 40%-87% [6]. Preliminary efficacy results from several studies show that this target has high druggability potential. In this study, IBI389 has demonstrated encouraging preliminary efficacy and tolerable safety in patients with advanced gastric tumors, suggesting the possibility of further exploration in this indication."

About IBI389 (anti-CLDN18.2/CD3 bispecific antibody)

IBI389 is an anti-CLDN18.2 T cell-engaging bispecific antibodies developed by Innovent Biologics. It induces immune synapse formations by linking CD3 molecules in T-cell receptor complexes and CLDN18.2 antigens on the surfaces of tumor cells. Therefore, IBI389 stimulates T-cell activation, resulting in cytolytic protein production, inflammatory cytokine release and further T-cell proliferation, which eventually leads to durable anti-tumor effects. Based on urgent clinical needs, Innovent has conducted clinical studies to explore the efficacy and safety of IBI389 as a monotherapy or in combination with various advanced malignancies.

On June 2, 2024 CatalYm reported positive new follow-up results from its ongoing "GDFATHER" Phase 1/2a trial (GDF-15 Antibody-mediaTed Human Effector Cell Relocation Phase 1/2a) (NCT04725474) in an oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2024 in Chicago (Press release, Catalym, JUN 2, 2024, View Source;to-Last-Line-Metastatic-NSCLC-Urothelial-and-Hepatocellular-Cancer-Patients-Treated-with-VisugromabNivolumab-Combination [SID1234643958]). Featuring matured data from the non-small cell lung cancer (NSCLC) and urothelial cancer (UC) cohorts, as well as novel, early data for the hepatocellular carcinoma (HCC) cohort and an additional biomarker cohort, the presentation highlighted that treatment with a combination of CatalYm’s lead candidate, visugromab, combined with the anti-PD-1 antibody nivolumab achieves compelling deep and durable anti-tumoral activity in anti-PD-1/PD-L1 relapsed/refractory patients as defined by strict criteria. The combination of visugromab and nivolumab further demonstrates an excellent safety and tolerability profile. Visugromab is a monoclonal antibody designed to neutralize the tumor-produced Growth Differentiation Factor-15 (GDF-15), a central mediator of immune resistance to cancer therapies.

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The oral presentation by International Coordinating Investigator Prof. Ignacio Melero, MD, PhD, Co-Director of Immunology and Immunotherapy (CIMA) at the Universidad de Navarra, Pamplona/Spain, provides further evidence for the potential of visugromab to improve the clinical response depth and duration for patients with advanced, metastatic tumors.

"These recent data continue to impress us with the significant ability to generate deep partial and complete responses with enormous durability in heavily pretreated patients that have failed their approved therapies including prior anti-PD-(L)1 treatment as defined by strict criteria," said Prof. Dr. Eugen Leo, Chief Medical Officer at CatalYm. "Remarkably, more than half of all responders experienced a response level/depth as per RECIST 1.1 (up to lasting CR) that had not been achieved on their prior/initial anti-PD-(L)1 treatment. This demonstrates that GDF-15 blockade by visugromab can induce a remission depth and durability, and long-term immunologic tumor control that other cancer immunotherapies could not induce. Visugromab may have the potential to bring us a major step closer to finally providing deep long-term tumor control and potentially cure for metastatic solid tumor patients with non-squamous NSCLC, UC, and HCC."

Summary of Key Clinical Results:

The matured results from the Phase 2a indication-specific cohorts for NSCLC, UC, and all HCC so far treated show the following Objective Response Rates (ORR):
non-squamous NSCLC: ORR of 19.0% (4/21), with 2 partial responses (PR) and 2 complete responses (CR)
UC: ORR of 19.2% (5/26), with 4 PR and 1 CR
HCC: ORR of 20.0% (4/20), with 3 PR and 1 CR in the primary early readout
The DoR results indicate that visugromab may have a significant impact on deepening and prolonging responses to checkpoint inhibitor (CPI) therapy:
non-squamous NSCLC and UC: mean DoR surpassed 15 and 14 months, respectively, with 7/9 responses ongoing
HCC: data still maturing with 12 patients ongoing on study treatment at data cut-off in the newly initiated cohort
Overall, in a total of 90 patients with the above indications treated in various cohorts (including a biomarker-oriented cohort with varying tumor types), an ORR of 16.7% across all three main tumor types is currently observed, with data partly maturing further.
In totality, 8/15 RECIST 1.1 responders (53.3%) experienced a response level/depth (PR, CR) that had not been achieved with their initial CPI therapy:
Complete responses (CRs): Among the 4 patients who achieved CR, 3 had no prior CR on any treatment regimen, including previous CPI treatments.
Partial responses (PRs): 5/11 patients who achieved PR had no RECIST 1.1 response at all on prior CPI treatments.
The combination of visugromab with nivolumab showed excellent overall tolerability, with a safety profile very similar to nivolumab treatment alone:
most Treatment-Emergent Adverse Events (TEAEs) were mild to moderate
only 8.1% of patients experienced severe TEAEs (Grade ≥ 3)
Patient sample analyses strongly support the involvement of GDF-15 in the creation of an immunosuppressed tumor microenvironment and highlight the therapeutic potential of GDF-15 neutralization in these indications:
Elevated serum levels of GDF-15 were shown to correlate inversely with intratumoral T cell numbers and their proliferation in samples of patients with non-squamous NSCLC, UC, and HCC.
Blockade of GDF-15 by visugromab, in combination with nivolumab treatment, resulted in the rise of serum interferon-γ levels, a critical cytokine for the stimulation of an immune response, in NSCLC and UC patients.
Blockade of GDF-15 by visugromab, in combination with nivolumab treatment, resulted in the rise of serum interferon-γ inducible chemokines CXCL9 and CXCL10 which remained significantly elevated over the monitoring period of six weeks.
Additional preclinical studies indicated that GDF-15 was significantly elevated by standard cancer treatments, specifically e.g. platinum-based chemotherapies, checkpoint inhibitor treatment, and respective combinations. This is another layer of support for the significant role of GDF-15 in the development of immune resistance to these treatment regimens and reason to develop visugromab in the first- and second- line settings where these agents are in standard use.
"We have designed a broad Phase 2b development plan to thoroughly investigate where visugromab can have its biggest impact for patients. These new results further confirm that neutralizing GDF-15 may be a critical strategy in overcoming cancer therapy resistance by breaking immunosuppressive barriers that currently limit therapeutic outcomes," said Phil L’Huillier, Managing Director and Chief Executing Officer at CatalYm. "Validated by the strong clinical and preclinical data on visugromab’s mechanism of action and GDF-15’s relevance in therapeutic resistance to date, we will now investigate the clinical benefit of visugromab in first- and second-line treatment and there in combination with standard-of-care that has been shown to increase GDF-15 levels further on top of the tumoral production of GDF-15. It is our goal to significantly improve patient responses and establish a new benchmark in cancer care."

The Phase 2a GDFATHER-2 program was initiated in March 2022. The ongoing study consists of two segments with up to seven cohorts and is expected to enroll over 200 patients in various cohorts. An evaluation of potential response-predictive biomarker(s) is ongoing. Based on a previous positive readout presented at the ESMO (Free ESMO Whitepaper) IO Congress in 12/2023, CatalYm is in preparations to launch randomized, controlled studies in several major cancer indications in combination with checkpoint inhibitors and standard-of-care in first- and second-line treatment in the first half of 2025.

Presentation Details

Title: Effects of neutralization of tumor-derived immunosuppressant GDF-15 on anti-PD-1 activity in anti-PD-(L)1 relapsed/refractory non-squamous NSCLC, urothelial, and hepatocellular cancer

Presenter: Dr. Ignacio Melero Bermejo, MD | Clinica Universidad de Navarra

Abstract Number: 2513

Date and time: Sunday, June 2, 2024, from 11:30 AM – 1:00 PM CDT

About the GDFATHER-2 Trials

The GDFATHER-2 trial (GDF-15 Antibody-mediaTed Human Effector cell Relocation Phase 2) (NCT04725474) is the Phase 2a part of the ongoing Phase 1/2a trial with several cohorts investigating the effect of visugromab (CTL-002) in combination with a PD-1 checkpoint inhibitor in patients in various advanced-stage/last-line and by strict criteria anti-PD1/PD-L1 relapsed/refractory solid tumor types. The study can enroll up to 200 patients and has extensive biomarker-evaluations integrated to assess for potential responder patient population identification or similar.

About Visugromab (CTL-002)

Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by reenabling immune cell activation and tumor infiltration. Visugromab has demonstrated a good safety profile and potent and durable anti-tumor efficacy in combination with anti-PD-1 treatment in advanced cancer patients The antibody is currently being investigated in ongoing Phase 2a studies in multiple solid tumor indications.

On June 2, 2024 GSK plc (LSE/NYSE: GSK) reported positive results from an interim analysis of the DREAMM-8 phase III head-to-head trial evaluating Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex), versus a standard of care, bortezomib plus PomDex, as a second line and later treatment for relapsed or refractory multiple myeloma (Press release, GlaxoSmithKline, JUN 2, 2024, View Source [SID1234643926]). These late-breaking data, being presented today at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (31 May – 4 June) in Chicago, IL, were featured in the official ASCO (Free ASCO Whitepaper) press programme and simultaneously published in the New England Journal of Medicine.

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On the primary endpoint of progression-free survival (PFS), a statistically significant and clinically meaningful improvement (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.37-0.73], p-value<0.001) was observed with the belantamab mafodotin combination (n=155) compared to the bortezomib combination (n=147). At a median follow-up of 21.8 months, the median PFS was not yet reached (95% CI: 20.6-not yet reached [NR]) with the belantamab mafodotin combination compared to 12.7 months (95% CI: 9.1-18.5) in the bortezomib combination. At the end of one year, 71% (95% CI: 63-78) of patients in the belantamab mafodotin combination group compared to 51% (95% CI: 42-60) in the bortezomib combination group were alive and had not progressed. A benefit for belantamab mafodotin plus PomDex was observed across all pre-specified subgroups including those with poor prognostic features, such as patients who were refractory to lenalidomide and patients with high-risk cytogenetics.

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "With the robust results from the DREAMM-8 phase III head-to-head trial, we now have consistent data from two phase III trials supporting the potential for Blenrep combinations to redefine the treatment of multiple myeloma at or after first relapse. This is exciting news given the high unmet need for new and efficacious combinations once patients relapse or stop responding to initial treatments. We continue to share data and discuss our path forward with regulators."

A positive overall survival (OS) trend was observed but not statistically significant (HR: 0.77 [95% CI: 0.53-1.14]) at the interim analysis. OS follow-up continues and further analyses are planned. At the end of one year, 83% (95% CI: 76-88) of patients were alive in the belantamab mafodotin combination group versus 76% (95% CI: 68-82) in the bortezomib combination group. The safety and tolerability profile of the belantamab mafodotin combination was broadly consistent with the known profile of the individual agents.

Suzanne Trudel, MD, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said: "The profound progression-free survival benefit seen in DREAMM-8 highlights the potential for belantamab mafodotin, when used with pomalidomide and dexamethasone, to improve outcomes for patients with relapsed/refractory multiple myeloma. This combination may have potential to redefine treatment of multiple myeloma at or after first relapse, a setting where patients may benefit from novel therapies.

Similar to the results seen in the DREAMM-7 phase III head-to-head trial, in DREAMM-8 the belantamab mafodotin combination also resulted in clinically meaningful improvements consistently across secondary efficacy endpoints, showing that the belantamab mafodotin combination resulted in deeper and more durable responses compared to the bortezomib combination. Key improvements included rate of complete response (CR) or better (more than twofold improvement); minimal residual disease (MRD) negativity rate (nearly fivefold improvement); and duration of response (median not yet reached with the belantamab mafodotin combination versus 17.5 months with the bortezomib combination).

Key and other secondary endpoint summaries are listed below.

Key and Other Secondary Endpoints
Endpoint belantamab mafodotin + pomalidomide and dexamethasone (BPd)
(n= 155) pomalidomide + bortezomib and dexamethasone (PVd)
(n=147)
ORR (overall response rate), % (95% CI)

77% (70.0-83.7)

72% (64.1-79.2)

sCR (stringent complete
response), %

9%

3%

CR (complete response),
%

31%

14%

VGPR (very good partial
response), %

24%

22%

PR (partial response), %

14%

34%

CR or better rate
(sCR+CR), % (95% CI)

40% (32.2-48.2)

16% (10.7-23.3)

VGPR or better rate
(sCR+CR+VGPR), %
(95% CI)

64% (55.8-71.4)

38% (30.2-46.5)

MRD negativity rate* %
(95% CI)

23.9% (17.4-31.4)

4.8% (1.9-9.6)

Duration of response
(months), median (95% CI)

NR (24.9-NR)

17.5 months (12.1-26.4)

Overall Survival**
HR (95% CI)  0.77 (0.53-1.14)
* Measured in patients with a sCR or CR.
** Follow-up for OS is ongoing.
NR: Not reached.

Grade 3 or higher non-ocular adverse events (AEs) of clinical interest in the belantamab mafodotin combination versus bortezomib combination arms, respectively, included neutropenia (57% versus 39%; 42 patients/100 person-years in both arms); thrombocytopenia (38% versus 29%; 28 versus 31 patients/100 person-years); and pneumonia (17% versus 8%; 13 versus 8 patients/100 person-years).

Eye-related side effects, a known risk of treatment with belantamab mafodotin, were generally reversible, manageable with dose modifications, and led to low (9%) treatment discontinuation rates. Grade 3 or higher ocular adverse events occurred in 43% of patients receiving the belantamab mafodotin combination (Grade 3: 42%; Grade 4: 1%). Most commonly reported grade 3 or higher ocular symptoms included blurred vision (Grade 3: 17%; Grade 4: 0), dry eye (Grade 3: 8%: Grade 4: 0), and foreign body sensation in the eyes (Grade 3: 6%; Grade 4: 0). Fifty-one patients (34%) with a best corrected visual acuity (BCVA) of 20/25 or better in at least one eye at baseline had a worsening in both eyes to 20/50 or worse. At the time of this analysis, the first occurrence of such events had improved in 92% of these patients, and resolved in 85%, with a median time to resolution of 57 days (range: 14-451 days).

Global health status quality of life (QOL), as measured by the EORTC-QLQ-C30 remained stable in both treatment arms over time, suggesting that treatment did not lead to any decline in overall health related QOL.

The DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical development programme continues to evaluate the potential of belantamab mafodotin in early lines of treatment and in combination with novel therapies and standard of care treatments. DREAMM-8 is the second phase III head-to-head belantamab mafodotin combination trial in second line and later treatment for multiple myeloma to report positive results. Positive findings from DREAMM-7, a phase III head-to-head trial evaluating belantamab mafodotin in combination with bortezomib and dexamethasone (BorDex) versus daratumumab plus BorDex in the same treatment setting, were presented1 at the ASCO (Free ASCO Whitepaper) Plenary Series on 6 February 2024, shared in an encore presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, and published in the New England Journal of Medicine.

About DREAMM-8
The DREAMM-8 phase III clinical trial is a multicentre, open-label, randomised trial evaluating the efficacy and safety of belantamab mafodotin in combination with PomDex compared to a combination of bortezomib and PomDex in patients with relapsed/refractory multiple myeloma previously treated with at least one prior line of multiple myeloma therapy, including a lenalidomide-containing regimen, and who have documented disease progression during or after their most recent therapy. Compared to the patient population studied in the DREAMM-7 trial, patients in DREAMM-8 were more heavily pre-treated in that all had prior exposure to lenalidomide, 75% were refractory to lenalidomide, 25% had prior daratumumab exposure and of those most were daratumumab refractory.

A total of 302 participants were randomised at a 1:1 ratio to receive either belantamab mafodotin plus PomDex, or bortezomib plus PomDex.

The primary endpoint is PFS as per an independent review committee. Key secondary endpoints include OS, minimal residual disease negativity as assessed by next-generation sequencing, and duration of response. Other secondary endpoints include ORR, patient-reported quality of life outcomes, adverse events, eye exam findings, and laboratory investigations.

About multiple myeloma
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.2,3 There are approximately 176,000 new cases of multiple myeloma diagnosed globally each year.4 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.5

About Blenrep
Blenrep is an antibody-drug conjugate comprising a humanised B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.

Refer to the Blenrep UK Summary of Product Characteristics6 for a full list of adverse events and the complete important safety information in the United Kingdom.

On June 2, 2024 Innovent Biologics, Inc. ("Innovent") (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 that results from the pivotal Phase 2 TRUST-I study conducted in China evaluating taletrectinib, next-generation ROS1 tyrosine kinase inhibitor (TKI), were published today in the Journal of Clinical Oncology (JCO) and will be highlighted in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Innovent Biologics, JUN 2, 2024, View Source [SID1234643943]).

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Data were reported from 173 patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) who were treated with taletrectinib. Results showed taletrectinib shrank tumors (confirmed objective response rate, cORR, as assessed by an independent review committee, IRC) in 91% of patients who were ROS1 TKI-naïve and 52% of patients who had previously been treated with crizotinib (ROS1 TKI-pretreated). Taletrectinib continued to show robust activity in patients with disease that spread to the brain, as well as in patients with acquired resistance mutations, including G2032R.

After median follow-up of 23.5 months in TKI-naïve patients, median duration of response (IRC-assessed) and median progression-free survival (IRC-assessed) were not reached. After median follow-up of 9.7 months in TKI-pretreated patients, median duration of response and median progression-free survival were 10.6 months and 7.6 months, respectively. Taletrectinib’s safety profile was consistent with previous reports, with a low incidence of neurologic treatment-emergent adverse events (TEAEs).

Based on positive results from the pivotal Phase 2 TRUST-I study, two new drug applications (NDA) of taletrectinib have been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China, and granted priority review designations, for first-line and second-line treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC.

"Current treatments for advanced ROS1-positive NSCLC have significant limitations, and people living with this disease remain in need of new options that are both well tolerated and offer durable responses," said Caicun Zhou, M.D., Ph.D., Principal Investigator of the TRUST-I study and Professor and Director of the Department of Oncology at Shanghai East Hospital, Tongji University. "These TRUST-I results reinforce taletrectinib’s strong efficacy and favorable safety profile, with longer follow-up, taletrectinib continues to show high and durable overall responses, robust intracranial and G2032R activity, with a low incidence of neurologic AEs. We look forward to taletrectinib benefits ROS1-positive NSCLC patients in the near future."

Dr. Hui Zhou, Senior Vice President of Innovent Biologics, stated, " The updated data of the TRUST-I study shows remarkably durable response and meaningful clinical benefits of taletrectinib for ROS1-positive NSCLC patients. We will continue close communications with our partner and regulatory authorities in China, hoping to bring this new generation of targeted therapy to patients with ROS1-positive NSCLC in China."

About ROS1-positive NSCLC

More than one million people globally are diagnosed with NSCLC annually, the most common form of lung cancer. It is estimated that approximately 1-3% of people with NSCLC are ROS1-positive. Up to 35% of people newly diagnosed with metastatic ROS1-positive NSCLC have tumors that have spread to their brain (brain metastases), increasing up to 55% for those whose cancer has progressed following initial treatment. While people with other types of lung cancer have seen great advances, there has been limited progress for people with ROS1-positive NSCLC who remain in need of new options.

About Taletrectinib

Taletrectinib is an oral, potent, central nervous system-active, selective, next-generation ROS1 inhibitor specifically designed for the treatment of patients with advanced ROS1-positive NSCLC. Taletrectinib is being evaluated for the treatment of patients with advanced ROS1-positive NSCLC in two Phase 2 single-arm pivotal studies: TRUST-I (NCT04395677) in China, and TRUST-II (NCT04919811), a global study. Taletrectinib has been granted Breakthrough Therapy Designations by both the U.S. Food and Drug Administration (FDA) and China’s National Medical Products Administration (NMPA) for the treatment of patients with advanced or metastatic ROS1-positive NSCLC. Based on results of the TRUST-I clinical study, China’s NMPA has accepted and granted Priority Review Designations to New Drug Applications for taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who either have or have not previously been treated with ROS1 tyrosine kinase inhibitors (TKIs).

In 2021, Innovent and AnHeart Therapeutics, a Nuvation Bio (NYSE: NUVB) Company, entered into an exclusive license agreement for the co-development and commercialization of taletrectinib in Greater China, including mainland China, Hong Kong, Macau and Taiwan.

About Phase 2 TRUST-I Study Results

TRUST-I (NCT04395677) is a pivotal Phase 2, multicenter, single-arm, open-label study evaluating taletrectinib as a monotherapy in 173 patients with advanced ROS1-positive NSCLC in China who either had not previously been treated with a ROS1 TKI (TKI-naïve) or had previously been treated with crizotinib (TKI-pretreated). Almost all patients received 600 mg of taletrectinib orally once-a-day in 21-day treatment cycles. 21% of TKI-naïve patients and 34% of TKI-pretreated patients had received prior chemotherapy, respectively. The primary endpoint of this registrational study was cORR as assessed by IRC, and key secondary endpoints included duration of response (DOR), progression-free survival (PFS), and safety.

As of November 29, 2023, results from TRUST-I as assessed by an IRC showed:

In TKI-naïve patients (n=106):

90.6% of patients’ tumors shrank in response to taletrectinib treatment (cORR).
Taletrectinib shrank brain tumors in 87.5% of people who had measurable central nervous system tumors (n=8; intracranial cORR).
After median follow-up of 23.5 months, median duration of response and median progression-free survival were not reached.
At two years, 78.6% of patients who responded to taletrectinib treatment were still responding and 70.5% of patients were still progression-free.
In TKI-pretreated patients (n=66):

51.5% of patients’ tumors shrank in response to taletrectinib treatment (cORR).
Taletrectinib shrank brain tumors in 73.3% of people who had measurable central nervous system tumors (n=15; intracranial cORR).
Taletrectinib shrank tumors in 66.7% of patients with G2032R mutations (n=12).
After median follow-up of 9.7 months, median duration of response was 10.6 months and median progression-free survival was 7.6 months.
At nine months, 69.8% of patients who responded to taletrectinib treatment were still responding and 47.4% were still progression-free.
Taletrectinib’s safety profile was consistent with previous reports. The most frequent TEAEs were increased liver enzymes (increased aspartate aminotransferase: 76%; increased alanine aminotransferase: 68%); diarrhea (70%); vomiting (53%), and anemia (49%), most of which were grade 1 or 2. Incidence of neurologic TEAEs were low; the most common was dizziness (23%), most of which was grade 1. Discontinuations (5%) and dose reductions (19%) due to TEAEs were low.

The JCO publication, "Efficacy and Safety of Taletrectinib in Chinese Patients with ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study," is available at View Source

The corresponding oral presentation of the same name (Abstract #8520) will be delivered by Wei Li, M.D., a TRUST-I investigator and Professor at the Department of Medical Oncology at Shanghai East Hospital, Tongji University, at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting in the "Lung Cancer – Non-Small Cell Metastatic" session occurring today, Saturday, June 1, 2024, at 4:30-6:00 p.m. CT/5:30-7:00 p.m. ET.