On June 2, 2024 Leading international medical research company, MEDSIR, reported the results of the recent PRIMED clinical trial during the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting (Press release, MedSIR, JUN 2, 2024, View Source [SID1234643945]). Carried out under the company’s collaborative model, this Investigator-Initiated Trial (IIT) demonstrated the effectiveness of preventative administration of drugs to treat the common side effects of neutropenia and diarrhea that can occur while taking sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2 that has extended overall survival for patients with pretreated triple negative and HR-positive/HER2-negative advanced breast cancer in two previous Phase 3 studies, ASCENT and TROPiCS-02. In the PRIMED study, adding primary prophylactic granulocyte colony-stimulating growth factors (G-CSF) and loperamide during the first two sacituzumab govitecan treatment cycles led to clinically meaningful reductions in neutropenia and diarrhea, lowering the need for dose reductions, treatment interruptions, and permanent discontinuations.

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"This is an exciting finding that highlights the high potential of prophylactic strategies that can mitigate side effects to help keep patients on promising treatments, which was made possible by our collaborative research model," shared Dr. Antonio Llombart-Cussac, Senior Scientific Leader of MEDSIR. "By using a partnership model that combines the benefits of company-sponsored research with all the advantages of IITs, we are turning brilliant ideas into full clinical trials that will safely and efficiently advance cancer solutions. It is our hope that, by working together, we will continue to generate new opportunities for patients worldwide."

Among PRIMED study participants, the incidence of any grade of neutropenia (in the first two cycles) was 28%, compared to 63% and 70% in ASCENT and TROPiCS-02 (in the full study), respectively. The incidence of any grade diarrhea (in the first two cycles) was 34%, compared to 59% and 57% in ASCENT and TROPiCS-02 (in the full study), respectively. The other side effects PRIMED study participants experienced were consistent to the known safety profile of sacituzumab govitecan, with the exception of constipation, which occurred in 46% of patients during the first two cycles compared to 17% in ASCENT and 19% in TROPiC-02 (in the full study). However, most cases of constipation were mild, and no patients experienced adverse events that led to permanent treatment discontinuation.

The study, which is still ongoing to evaluate efficacy and collect longer-term safety data, enrolled 50 patients between February 2023 and September 2023 across 10 sites across Spain, providing them with G-CSF and loperamide during the first two sacituzumab govitecan treatment cycles (physician’s decision to continue after two cycles). These two drugs are commonly used to treat neutropenia and diarrhea, respectively, but are usually administered only after these side effects occur. In PRIMED, researchers wanted to test whether early administration of these drugs, before patients experienced any neutropenia or diarrhea, could reduce the incidence of these side effects and determine how this affected the need for dose reductions, treatment interruptions, and permanent discontinuations.

Showcasing Numerous Promising Collaborative Trials at ASCO (Free ASCO Whitepaper)

PRIMED was not the only trial MEDSIR presented during the ASCO (Free ASCO Whitepaper) Annual Meeting. It shared the results of several other recent and ongoing studies as well.

Recently published in The Lancet, MEDSIR’s PHERGain phase II trial (NCT03161353) demonstrated how a third of patients with HER2-positive early breast cancer could be safely treated without using chemotherapy. At the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, MEDSIR presented a subanalysis of this study comparing PET scan and magnetic resonance imaging (MRI) results; both tests that participants undergo to observe the evolution of their cancer. The comparative study shows tumor assessments can be analyzed with both PET scan and MRI. Although PET scan is the recommended imaging technique for early treatment response, this exploratory study suggests that MRI could alternatively guide the treatment when PET scan are not available.

MEDSIR’s PATHFINDER study evaluated the safety, tolerability, and preliminary efficacy of ipatasertib in combination with non-taxane chemotherapy in patients with advanced triple negative breast cancer who had previously experienced tumor progression after treatment with taxane chemotherapy. Study results revealed that combining ipatasertib with capecitabine and eribulin has an acceptable safety profile in these patients, but that adding ipatasertib alongside carboplatin plus gemcitabine proved to be intolerable. Additionally, the combination of ipatasertib and eribulin demonstrated encouraging efficacy, warranting further investigation.

TUXEDO-3, one of MEDSIR’s ongoing clinical trials in Austria and Spain, is the first study evaluating the efficacy and safety of patritumab deruxtecan as an anti-cancer therapy for patients with pretreated metastatic breast cancer and advanced non-small cell lung cancer with brain metastases, and metastatic solid tumors with leptomeningeal disease. If positive, this study could streamline the introduction of HER3-DXd as a new treatment for these patients who currently have very limited therapeutic options.

ABOUT UMMET CANCER NEEDS

Unmet cancer needs refer to gaps in resources, support, and treatment options that exist for cancer patients. Addressing unmet cancer needs is crucial to improving quality of life and outcomes for cancer patients. Through the collaborative work of healthcare providers, policymakers, and patient advocacy groups unmet cancer needs can be identified to help provide patients with comprehensive and quality care.

On June 2, 2024 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported that it has completed the submission of a Biologics License Application (BLA) to the United States (U.S.) Food and Drug Administration (FDA) for its investigational radiodiagnostic PET[1] agent, TLX250-CDx (Zircaix[2], 89Zr-DFO-girentuximab), for the characterisation of renal masses as clear cell renal cell carcinoma (ccRCC) (Press release, Telix Pharmaceuticals, JUN 2, 2024, View Source [SID1234643944]).

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The rolling BLA submission, initiated in December 2023[3] with timelines pre-agreed with the FDA, was based on Telix’s successful global Phase III ZIRCON[4] study in ccRCC. The clear cell variant of renal cancer is the most common and aggressive sub-type of kidney cancer. The ZIRCON study met all co-primary and secondary endpoints, demonstrating a sensitivity of 86%, specificity of 87% and a positive predictive value (PPV) of 93% for ccRCC, including in small, difficult to detect lesions[5].

As part of the BLA submission process, Telix has requested a Priority Review under the eligibility criteria of the Breakthrough Therapy designation[6]. If granted, this would potentially support an expedited review time. If Zircaix[2] is approved, TLX250-CDx will be the first targeted radiopharmaceutical imaging agent specifically for kidney cancer to be commercially available in the U.S. and further builds on Telix’s successful urology imaging franchise.

James Stonecypher, Chief Development Officer at Telix, stated, "Completing the BLA submission for TLX250-CDx represents a significant milestone for Telix as we bring our Breakthrough investigational kidney cancer imaging agent closer to market as a non-invasive diagnostic for patients. We believe TLX250-CDx is a natural follow-on product to Illuccix as it is targeted at the same clinical stakeholders, the urologist and urologic oncologist, and leverages the proven commercial and distribution infrastructure developed through the launch of Illuccix."

TLX250-CDx International Expanded Access

As part of Telix’s commitment to access to medicine, the Company has opened an expanded access program (EAP) in the U.S.[7], named patient programs (NPPs) in Europe, and a special access scheme (SAS) in Australia to allow continued access to TLX250-CDx outside of a clinical trial to patients for whom there are no comparable or satisfactory alternate options.

U.S. patients, or physicians who may have eligible patients in the U.S., can e-mail [email protected] or complete the form here for further information.

Physicians in Europe and Australia who may have eligible patients can email [email protected] and [email protected], respectively, for further information about TLX250-CDx named patient access.

Telix’s Policy on Offering Compassionate Use to Investigational Medicines can be downloaded at the following link.

For more information about ongoing clinical trials of TLX250-CDx, please visit View Source

About TLX250-CDx (Zircaix[2])

TLX250-CDx (Zircaix[2]) is a PET diagnostic imaging agent that is under development to characterise indeterminate renal masses as ccRCC or non-ccRCC in a non-invasive manner. Telix’s pivotal Phase III ZIRCON trial (ClinicalTrials.gov ID: NCT03849118) evaluating TLX250-CDx in 300 patients, of which 284 were evaluable, was completed in 2022 and met all primary and secondary endpoints, including showing 86% sensitivity and 87% specificity and a 93% positive-predictive value for ccRCC across three independent readers[5]. We believe this demonstrated the ability of TLX250-CDx to reliably detect the clear cell phenotype and provide an accurate, non-invasive method for diagnosing ccRCC. Confidence intervals exceeded expectations in all three readers, showing evidence of high accuracy and consistency of interpretation.

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.

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 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune, ophthalmology and other major diseases, reported that the clinical data of a randomized controlled Phase 1b study evaluating IBI310 (anti-CTLA-4 monoclonal antibody) in combination with sintilimab as neoadjuvant treatment of colon cancer was orally presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ClinicalTrials.gov, NCT05890742) (Press release, Innovent Biologics, JUN 2, 2024, View Source [SID1234643941]). The abstract was selected for ASCO (Free ASCO Whitepaper) Daily News coverage.

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Based on the promising Phase 1b results, Innovent has opened the Phase 3 trial (Neoshot) evaluating IBI310 in combination with sintilimab as neoadjuvant treatment of colon cancer. The Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has also granted Breakthrough Therapy Designation (BTD) for IBI310.

Neoadjuvant treatment of IBI310 (anti-CTLA-4 antibody) plus sintilimab (anti-PD-1 antibody) in patients with microsatellite instability-high/mismatch repair-deficient colorectal cancer: results from a randomized, open-labeled, Phase 1b study

Abstract #: 3505

In this Phase 1b study, the efficacy and safety of IBI310 in combination with sintilimab versus sintilimab as neoadjuvant therapy for resectable stage IIB-III MSI-H/dMMR colon cancer was evaluated.

As of February 4, 2024, 101 pts were enrolled and randomized to receive IBI310 plus sintilimab (n=52) or sintilimab alone (n=49). For per-protocol set, the pathologic complete response (pCR) rates in IBI310 plus sintilimab arm were significantly improved than sintilimab alone arm（80.0% vs 47.7%, p=0.0007）.
Treatment related adverse events (TRAEs) leading to surgery delay occurred in 2 pts (3.8%) in IBI310 plus sintilimab arm and 0 pt in sintilimab alone arm. Grade ≥3 immune-related adverse events (irAEs) occurred in 3 pts (5.8%) and in 4 pts (8.2%), respectively. IBI310 plus sintilimab did not increase safety risk compared to sintilimab alone, and did not affect the subsequent surgery.
The Principal Investigator of the study, Prof. Ruihua Xu from Sun Yat-sen University Cancer Center, stated, "At present, complete (R0) resection for some stage IIB-III colon cancer patients remain a significant challenge, along with risks of extensive trauma and poor prognosis. In particular, neoadjuvant chemotherapy is not effective in MSI-H/dMMR colon cancer, and the pCR rate is only about 5%[1]. This Phase 1b study was the first randomized study to demonstrate the significant higher pCR rate of the dual immunotherapy in MSI-H/dMMR colon cancer. Neoadjuvant treatment of IBI310 in combination with sintilimab is potentially practice-changing that could reduce the preoperative staging, narrow the scope of radical resection, increase the complete resection rate, reduce the requirement of adjuvant chemotherapy and decrease the incidence of relapse, so as to improve the long-term prognosis and potentially cure the patients. The Phase 3 clinical study (Neoshot) is ongoing in China, and we look forward to positive results from this study to provide a more effective treatment option for patients with MSI-H/dMMR colon cancer."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "There is a huge unmet clinical need for neoadjuvant therapy of resectable MSI-H/dMMR colon cancer in China. In this randomized, controlled Phase 1b study, IBI310 in combination with sintilimab significantly improved pCR rate than sintilimab alone in MSI-H/dMMR CRC with manageable safety profile. Based on the strong results of this study, we moved IBI310 in combination with sintilimab into Phase 3 trial (Neoshot) earlier this year, and we are looking forward to the positive results."

About IBI310
IBI310 is a fully human monoclonal antibody injection independently developed by Innovent. IBI310 can specifically bind cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), thereby blocking CTLA-4 mediated T cell inhibition, promoting T cell activation and proliferation, improving tumor immune response, and achieving anti-tumor effects.

About Sintilimab
Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells[2].

In China, sintilimab has been approved and included in the National Reimbursement Drug List (NRDL) for seven indications. The updated NRDL reimbursement scope for TYVYT (sintilimab injection) includes:

For the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy;
For the first-line treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
For the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer who progressed after EGFR-TKI therapy;
For the first-line treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
For the first-line treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
For the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
For the first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
Besides, the New Drug Application ("NDA") for the combination of sintilimab and fruquintinib for the treatment of patients with advanced endometrial cancer with pMMR or non-MSI-H tumors that have failed prior systemic therapy but are not candidates for curative surgery or radiation has been accepted and granted priority review by the NMPA.

In addition, two clinical studies of sintilimab have met their primary endpoints:

Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
Phase 3 study of sintilimab monotherapy as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.
Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s).