On January 18, 2024 Elevar Therapeutics, Inc., a majority-owned subsidiary of HLB Co., Ltd. and a fully integrated biopharmaceutical company dedicated to elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, reported that it will present two posters and give an Industry Expert Theater presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO GI) (Press release, Elevar Therapeutics, JAN 18, 2024, View Source [SID1234639327]).

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The posters examine post hoc analyses of clinical data and patient-reported outcomes tied to Elevar’s CARES-310 study (NCT03764293), which assessed the combination of the company’s drug candidates camrelizumab, a PD-1 inhibitor, in combination with rivoceranib, an oral TKI, as a first-line therapy for unresectable hepatocellular carcinoma (uHCC).

ASCO GI will be held Jan. 18-20, 2024, at the Moscone Convention Center (West) in San Francisco, and online. Elevar’s poster presentations are:

Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Date and Time: Jan. 19, 2024, at 12:30 p.m. – 2 p.m. PT Abstract Number: 509 Abstract Title: Impact of baseline liver function on survival outcomes in patients with unresectable hepatocellular carcinoma (uHCC) treated with camrelizumab + rivoceranib vs sorafenib: A post hoc analysis of study CARES-310.

Date and Time: Jan. 19, 2024, at 12:30 p.m. – 2 p.m. PT Abstract Number: 456 Abstract Title: Patient-reported outcomes (PROs) <65 or ≥ 65 years old (yo) from CARES-310 camrelizumab + rivoceranib vs sorafenib as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).

Industry Expert Theater presentation details:

Date and Time: Jan. 19, 2024; 5:15 p.m. – 6 p.m. PT Presentation Title: Impact of liver function on survival outcomes during treatment with camrelizumab + rivoceranib (cam+rivo) vs sorafenib in uHCC patients: therapeutic implications Speaker: Natalia Raphael, Ph.D., Elevar executive director of medical affairs

Session Description: Impact of baseline liver reserve and drug induced hepatotoxicity (DIH) on survival outcomes assessed; time to resolution/discontinuation, impact on QoL of DIH determined. The results of this post-hoc analysis may have implications for selection of initial and subsequent therapies for uHCC patients.

"Elevar is pleased that CARES-310 continues to yield results that support the combination of camrelizumab plus rivoceranib as a potentially important therapy for those confronted with hepatocellular carcinoma," said Saeho Chong, Elevar chief executive officer. "We look forward to detailing these findings while meeting with our peers at ASCO (Free ASCO Whitepaper) GI."

One ASCO (Free ASCO Whitepaper) GI poster is a post hoc analysis of the impact of baseline liver function on survival outcomes in patients with uHCC treated with camrelizumab and rivoceranib in CARES-310. The analysis found the efficacy of camrelizumab plus rivoceranib was superior to sorafenib regardless of baseline liver function as measured by both albumin-bilirubin (ALBI) grade and Child-Pugh (CP) class. Despite a higher rate of grade 3/4 adverse effects, there was no detrimental effect of camrelizumab plus rivoceranib on liver function and overall survival in patients with both mildly and moderately preserved liver function compared to sorafenib.

The other poster assessed patient-reported outcomes during CARES-310. Camrelizumab plus rivoceranib demonstrated clinically meaningful benefits in key aspects of the patient experience. Although patients treated with camrelizumab and rivoceranib exhibited higher rate of treatment-related adverse events, the combination did not adversely impact quality of life when compared to sorafenib.

Supported by the CARES-310 results, Elevar and Jiangsu Hengrui Pharmaceuticals Co., Ltd. in May 2023 submitted a new drug application (rivoceranib) and biologics license application (camrelizumab) to the U.S. Food and Drug Administration (FDA) for the combination as a first-line treatment option for uHCC. The FDA assigned Prescription Drug User Fee Act (PDUFA) target action dates in May 2024.

About Hepatocellular Carcinoma (HCC) HCC is the most common type of primary liver cancer. It most frequently occurs in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. HCC typically has a poor prognosis and a lack of treatment options and is therefore a condition with an urgent medical need.

About Rivoceranib Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), is a highly potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway for tumor angiogenesis. VEGFR-2 inhibition is a clinically validated approach to limit tumor growth and disease progression. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include uHCC (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf). Rivoceranib was the first TKI approved in gastric cancer in China (November 2014). It is also approved in China in combination with camrelizumab as a first-line treatment for uHCC (February 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in uHCC (U.S.). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, Jiangsu Hengrui Pharmaceuticals Company Ltd., (Hengrui Pharma), under the brand name Aitan.

About Camrelizumab Camrelizumab (SHR-1210) is a humanized monoclonal antibody targeting the programmed death-1 (PD-1) receptor. Blockade of the PD-1/PD-L1 signaling pathway is a therapeutic strategy showing success in a wide variety of solid and hematological cancers. Camrelizumab is developed by Hengrui Pharma and has been studied in more than 6,000 patients. Currently, 50 clinical trials are underway in a broad range of tumors (including liver cancer, lung cancer, gastric cancer, and breast cancer) and treatment settings. Camrelizumab, under the brand name AiRuiKa, is currently approved for eight indications in China, including monotherapy for the treatment of HCC (second-line), in combination with rivoceranib as a treatment for uHCC (first-line), relapsed/refractory classic Hodgkin’s lymphoma (third-line), esophageal squamous cell carcinoma (second-line) and nasopharyngeal carcinoma (third-line or further) and in combination with chemotherapy for the treatment of non-small cell lung cancer (non-squamous and squamous), esophageal squamous cell carcinoma and nasopharyngeal carcinoma in the first-line setting. The U.S. Food and Drug Administration granted Orphan Drug Designation to camrelizumab for advanced HCC in April 2021. Elevar has rights to commercialize and develop Hengrui Pharma’s camrelizumab in combination with rivoceranib for unresectable hepatocellular carcinoma (uHCC) worldwide, excluding Greater China Region and Korea (Oct. 2023).

On January 18, 2024 Deciphera Pharmaceuticals, Inc. (NASDAQ: DCPH), a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines to improve the lives of people with cancer, reported the presentation of new long-term results from the INTRIGUE Phase 3 clinical study comparing QINLOCK (ripretinib) versus sunitinib in patients with advanced gastrointestinal stromal tumor (GIST) previously treated with imatinib (Press release, Deciphera Pharmaceuticals, JAN 18, 2024, View Source [SID1234639326]).

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The presentation titled "Overall survival and long-term safety with ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: final analyses from INTRIGUE" will be presented by John Zalcberg, M.D., Ph.D., Cancer Research Program, Monash University School of Public Health and Preventive Medicine and Department of Medical Oncology, Alfred Health, Melbourne, Victoria, Australia at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium and will be available on the Company’s website at www.deciphera.com/presentations-publications.

"These long-term clinical results demonstrate that the overall survival rate was similar for both QINLOCK and sunitinib, and that treatment with QINLOCK continued to show a favorable safety profile compared to treatment with sunitinib," said Dr. Zalcberg. "In addition, the data show that patient outcomes in the third-line setting are comparable for patients that were treated with either QINLOCK or sunitinib in the second line."

"The final results from INTRIGUE demonstrate the strong clinical activity of QINLOCK in the broader second-line GIST patient population," said Matthew L. Sherman, M.D., Chief Medical Officer of Deciphera. "Importantly, these results also indicate that third line treatment is not adversely impacted by treatment with QINLOCK in the second line and that QINLOCK continues to show a favorable safety profile compared to sunitinib."

Results of INTRIGUE Study Long-Term Follow-Up

In INTRIGUE, 453 patients in the all-patient intent-to-treat population (AP-ITT) with second-line GIST were randomized 1:1 to receive QINLOCK 150 mg once daily (n=226) or sunitinib 50 mg once daily (4 weeks on/2 weeks off) (n=227) of which 444 patients received treatment.

In the primary analysis of the AP-ITT population based on a data cut of September 1, 2021, while the primary endpoint was not achieved, QINLOCK demonstrated similar efficacy with a median progression-free survival (PFS) of 8.0 months versus 8.3 months for sunitinib (hazard ratio [HR] 1.05, nominal p=0.72). There were fewer patients with Grade 3/4 drug-related treatment emergent adverse events (TEAE) with QINLOCK (26.5%) compared with sunitinib (55.2%). Based on the primary results from the INTRIGUE study, QINLOCK was included in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for GIST (version 1.2023) as a preferred second-line regimen for patients with advanced GIST who are intolerant to sunitinib.

The final analysis includes 18 months of additional follow up after the primary analysis based on a data cut of March 15, 2023. Key highlights from the final results presented include the following:

Overall Survival (OS)

There were 211 OS events (46.6%) in the AP-ITT population with median duration of follow-up in the QINLOCK and sunitinib arms of 35.1 months and 34.1 months, respectively.
Median OS in the AP-ITT population was similar with QINLOCK (35.5 months) versus sunitinib (31.5 months) (HR 0.86; 95% CI, 0.65 to 1.13; nominal p= 0.275).
Safety and Tolerability

Among the 444 patients treated, 9.0% of patients remained on treatment at the time of data cutoff including 12.6% of 223 patients treated with QINLOCK and 5.4% of 221 patients treated with sunitinib.
The long-term safety profile of QINLOCK was consistent with the primary analysis.
Fewer patients had Grade 3/4 drug-related TEAEs with QINLOCK (27.4%) versus sunitinib (57.9%).
Dose interruptions and reductions as well as treatment discontinuations due to TEAEs were lower with QINLOCK versus sunitinib. Fewer patients discontinued treatment due to any TEAE for QINLOCK (4.9%) versus sunitinib (9.0%).
The most common TEAEs in the QINLOCK arm were alopecia, fatigue, and myalgia. The most common TEAEs in patients treated with sunitinib were palmar-plantar erythrodysesthesia syndrome, diarrhea, and hypertension.
Exploratory Analysis: Efficacy of Next-Line Therapy

Median PFS on the next line of therapy after protocol treatment was similar for QINLOCK (7.7 months) versus sunitinib (7.4 months) in the AP-ITT population (HR 1.03; 95% CI, 0.78 to 1.35).
Following study treatment discontinuation, the most common third-line therapy was sunitinib for patients in the QINLOCK arm (59.7%) and regorafenib for patients in the sunitinib arm (42.7%).
Patients in the QINLOCK arm who received third-line sunitinib had a median PFS on next line of therapy of 8.5 months compared with 6.3 months for patients in the sunitinib arm who received third-line regorafenib (HR 0.90; 95% CI, 0.66 to 1.24).
Details of the poster presentation are as follows:

Title: Overall survival and long-term safety with ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: final analyses from INTRIGUE
Author: John Zalcberg, M.D., Ph.D., Monash University School of Public Health and Preventive Medicine
Session: A: Cancers of the Esophagus and Stomach and Other GI Cancers
Abstract #: 748
Date and Time: Thursday January 18, 2024 11:45 AM – 1:15 PM PT

In January 2024, Nature Medicine published the results of the exploratory ctDNA analysis from INTRIGUE showing substantial clinical benefit of QINLOCK compared to sunitinib in second-line GIST patients with mutations in KIT exon 11 and 17/18 only. Patients with mutations in KIT exon 11 and 17/18 had improved progression-free survival, objective response rate, and overall survival with QINLOCK versus sunitinib.

Based on the results of this prespecified exploratory objective in INTRIGUE, the Company is enrolling the INSIGHT pivotal Phase 3 clinical study of QINLOCK in second-line GIST patients with mutations in KIT exon 11 and 17/18 only.

About the INSIGHT Study

The INSIGHT Phase 3 clinical study is a randomized, global, multicenter, open-label study to evaluate the efficacy and safety of QINLOCK compared to sunitinib in patients with GIST previously treated with imatinib with mutations in KIT exon 11 and 17/18 (excluding patients with mutations in KIT exons 9, 13, or 14). In the study, 54 patients will be randomized 2:1 to either QINLOCK 150 mg once daily or sunitinib 50 mg once daily for four weeks followed by two weeks without sunitinib. The primary endpoint is PFS as determined by independent radiologic review using modified RECIST 1.1 criteria. Secondary endpoints include ORR as determined by independent radiologic review using modified RECIST 1.1 criteria and OS.

About the INTRIGUE Study

The INTRIGUE Phase 3 clinical study is a randomized, global, multicenter, open-label study to evaluate the efficacy and safety of QINLOCK compared to sunitinib in patients with GIST previously treated with imatinib. In the study, 453 patients were randomized 1:1 to either QINLOCK 150 mg once daily or sunitinib 50 mg once daily for four weeks followed by two weeks without sunitinib. As previously reported, the study did not achieve the primary efficacy endpoint of PFS as determined by independent radiologic review using modified RECIST 1.1 criteria. The statistical analysis plan included a hierarchical testing sequence that included testing in patients with a KIT exon 11 primary mutation and then in the AP-ITT population. In patients with a KIT exon 11 primary mutation (n=327), QINLOCK demonstrated a median PFS of 8.3 months compared to 7.0 months for the sunitinib arm (HR 0.88, p=0.360). Although not formally tested due to the rules of the hierarchical testing sequence, in the AP-ITT population QINLOCK demonstrated a median PFS of 8.0 months compared to 8.3 months for the sunitinib arm (HR 1.05, nominal p=0.72). QINLOCK was generally well tolerated. Fewer patients in the QINLOCK arm experienced Grade 3/4 treatment-emergent adverse events compared to sunitinib (41.3% vs. 65.6%). Similarly, there were fewer patients with Grade 3/4 drug-related TEAEs with QINLOCK (26.5%) compared with sunitinib (55.2%).

On January 18, 2024 Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), reported data from the lead-in portion of the Phase 2 clinical trial evaluating casdozokitug (casdozo), a selective and potent IL-27-targeting antibody, in combination with atezolizumab (atezo) and bevacizumab (bev) in treatment naïve patients with unresectable locally advanced or metastatic hepatocellular carcinoma (uHCC) (Press release, Coherus Biosciences, JAN 18, 2024, View Source [SID1234639325]). These data are being presented at the 2024 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium taking place January 18-20, 2024 at Moscone West in San Francisco, California. Interleukin (IL)-27 is an immunoregulatory cytokine involved in suppressing anti-tumor immune responses and an important new target for cancer treatment. Casdozo is a first-in-class antibody, and the only clinical stage immunomodulatory cytokine antagonist targeting IL-27.

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"Doublet immunotherapy combinations for the treatment of liver cancer have improved outcomes for patients for whom surgery is not an option or whose cancer has spread. However, not all patients respond to current therapy and novel treatment options that can further improve survival without added toxicity are needed," said Daneng Li, M.D., Associate Professor in the Department of Medical Oncology & Therapeutics Research and Co-Director, Liver Cancer Collaborative Program, City of Hope Comprehensive Cancer Center. "The addition of casdozo to standard of care is encouraging and supports further evaluation of cazdozo, and its novel anti-IL-27 mechanism, as part of triplet therapy in HCC. Additionally, each person with advanced HCC is unique with respect to their tumor, co-morbidities and other factors – the biomarker data showing an association of IL-27 biology and response to casdozo is particularly interesting and the potential to identify biomarkers of response would be an important benefit to patients with liver cancer."

"These impressive early clinical and immune activation data for casdozo in HCC demonstrating an ORR of 38%, including 3 complete responses, and a favorable safety profile add to the growing body of data supporting IL-27 as a promising novel target in combination therapy for advanced solid tumors," said Rosh Dias, M.D., Coherus’ Chief Medical Officer. "We now have data across several tumor types for casdozo demonstrating clinical activity. Our comprehensive clinical development program of ongoing and planned clinical trials including casdozokitug in combination with our anti-PD-1 antibody backbone of toripalimab-tpzi, will further advance our internal next-generation immuno-oncology combinations focused on overcoming immune suppression in the tumor microenvironment with the goal of extending survival and improving outcomes for patients."

Lead-in portion of Phase 2 clinical trial design
The open-label lead-in portion of the Phase 2 clinical trial evaluated casdozo in combination with atezo and bev in 30 patients with treatment-naïve uHCC. Patients received casdozo 10 mg/kg IV q3w, in combination with atezo (1200 mg) and bev (15 mg/kg). The primary endpoint of the lead-in portion of the study was safety and tolerability. Key secondary endpoints included progression-free survival (PFS) and overall response rate (ORR) based on investigator review per RECIST v1.1 (primary) and mRECIST (secondary), as well as disease control rate (DCR). Further [Phase 2] clinical development of cazdozo in HCC is planned to evaluate casdozo/toripalimab (anti-PD-1 antibody)/bev.

Lead-in portion of Phase 2 clinical trial data
As of the data cutoff date (November 9, 2023):
Triplet blockade of the IL-27, PD-(L)1 and VEGF pathways with casdozo/atezo/bev has an acceptable safety profile to date with promising antitumor activity in IO naïve HCC.

Triplet combination treatment was well tolerated with side effect profile consistent with known adverse event (AE) profiles of atezo/bev.
Encouraging early activity with casdozo/atezo/bev:
RECIST v1.1: ORR of 38% (n=29) with 11 durable objective responses including 3 complete responses and 8 partial responses (1 unconfirmed); median progression-free survival of 8.1 months and disease control rate of 58.6%.
mRECIST: ORR of 43% (n=28) with 12 durable objective responses including 3 complete responses and 9 partial responses (1 unconfirmed); median progression-free survival not reached and disease control rate of 60.7%.
Further analyses of samples from patients who responded to treatment (small n) indicate preliminary association between response and biomarkers of IL-27.
These results support continued evaluation of casdozo with VEGF and PD-(L)1 blockade in HCC. Coherus plans to evaluate the combination of casdozo/toripalimab-tpzi(Coherus’ anti-PD-1 antibody)/bev in future clinical trials.

Poster presentation details:
Title: Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VegF pathways with casdozokitug (casdozo, CHS-388) in combination with atezolizumab (atezo) and bevacizumab (bev) in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC)
Poster Board number: B15
Abstract number: 470
Date and Time: Friday, January 19, 2024, 12:30 – 2:00 pm PT
Presenter: Daneng Li, MD
Location: Level 1, West Hall, Moscone West

About Casdozokitug
Casdozokitug is a first-in-class human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Particular tumor types have been identified where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. Blocking IL-27 with casdozokitug in clinical trials has led to monotherapy tumor growth inhibition and partial responses in patients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) (NCT04374877). An ongoing trial is studying combinations with PD-(L)1 pathway blockade in NSCLC and a planned clnical trial will study the triplet combination of IL-27, PD-(L)1 and VEGF pathway blockade in hepatocellular carcinoma (HCC). Casdozokitug has been granted Orphan Drug designation and Fast Track designation for the treatment of refractory hepatocellular carcinoma from the FDA. It is the first IL-27 antibody to enter the clinic.

On January 18, 2024 BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported strategic financing from Blue Owl Capital (Blue Owl) and Canada Pension Plan Investment Board (CPP Investments), through a wholly owned subsidiary (CPPIB Credit) of CPPIB Credit Investments Inc., bringing in capital of up to $1.25 billion (Press release, BridgeBio, JAN 18, 2024, View Source [SID1234639324]).

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With these transactions, BridgeBio obtains financing from experienced healthcare investors who share the Company’s confidence in the anticipated launch of acoramidis as the potential backbone of therapy for transthyretin amyloid cardiomyopathy (ATTR-CM).

"We are excited to be working with a distinguished group of life sciences investors who are aligned with our view of acoramidis’ blockbuster market opportunity," said Brian Stephenson, Ph.D., CFA, Chief Financial Officer of BridgeBio. "Our newly strengthened balance sheet will enable us to serve ATTR-CM patients with a well-resourced launch of acoramidis, as well as patients with genetic diseases more broadly with multiple Phase 3 readouts for blockbuster indications anticipated over the next few years. Our increasing patient impact should allow us to diversify drivers of top line revenue in the near term and enable reinvestment into R&D paired with opportunistic business development."

The overall collaboration includes the following key features:

A royalty agreement with Blue Owl and CPPIB Credit:
$500 million cash payment upon FDA approval of acoramidis to help support the Company’s commercial launch in exchange for future royalties of 5% of worldwide net sales of acoramidis, both of which are subject to various conditions. This consists of $300 million from Blue Owl and $200 million from CPPIB Credit
Total royalty payments are capped at 1.9 times the invested capital, and the royalty agreement includes investment features (such as change of control provisions that apply prior to FDA approval) intended to provide broad strategic flexibility for BridgeBio going forward
A refinancing with Blue Owl of BridgeBio’s existing senior credit facility:
$450 million of committed capital funded at close to refinance BridgeBio’s existing senior credit facility, extending maturity from 2026 to 2029 and providing the Company with considerable operational flexibility
An additional tranche of up to $300 million, funded at the Company and Blue Owl’s mutual consent to support strategic corporate development activities
"Blue Owl is well-positioned to provide bespoke and scaled financing solutions to the most consequential companies in the life sciences sector," said Sandip Agarwala, Managing Director at Blue Owl Capital. "Acoramidis has demonstrated an impressive and differentiated clinical profile, and we believe it will be an important advancement in the treatment of ATTR-CM. Further, BridgeBio’s promising pipeline of late-stage targeted rare disease therapies address critical unmet needs in these underserved populations. We are pleased to support BridgeBio in its mission of bringing breakthrough medicines to patients."

"This investment in BridgeBio represents an opportunity to provide structured capital solutions to an innovative company in the healthcare space and leverage CPP Investments’ deep capabilities in life sciences," said David Colla, Managing Director and Head of Capital Solutions, CPP Investments. "Investments in leading therapies also help to diversify our capital allocations to income streams that are typically uncorrelated to the broader capital markets."

Morgan Stanley & Co. LLC acted as sole structuring agent on the transactions. Latham & Watkins served as legal advisor to BridgeBio and Cooley LLP advised Blue Owl.

On January 18, 2024 AskGene Pharma Inc. reported encouraging clinical results for ASKB589, an anti-CLDN18.2 antibody, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancer Symposium (ASCO-GI 2024) in San Francisco on January 18-20, 2024 (Press release, AskGene Pharmaceuticals, JAN 18, 2024, View Source [SID1234639323]).

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The results were from clinical trial NCT05632939, a Phase Ib/II, two-part, dose escalation and expansion study to evaluate the safety, tolerability, and anti-tumor activities of ASKB589 in combination with chemotherapy (CAPOX) and a PD-1 inhibitor as a first-Line treatment in patients with locally advanced, relapsed and metastatic gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma. As of December 20, 2023, a total of 62 patients with positive CLDN18.2 expression were dosed Q3W with ASKB589 combined with CAPOX and PD-1 inhibitor: 9 patients received ASKB589 at 6 mg/kg (n=3) and 10 mg/kg (n=6) in the dose escalation and 53 patients at 6 mg/kg in the dose expansion. Most of the enrolled patients had moderate to high CLDN18.2 expression (83.9%) and PD-L1 CPS ³1 (59.7%).

ASKB589 was safe and tolerated at both 6 and 10 mg/kg. No dose-limiting toxicity was observed, and maximum tolerated dose (MTD) was not identified during the escalation phase of the study. Most adverse events (AEs) were of mild severity (grade 1 or 2). The most common AEs were hypoalbuminemia (77.4%), nausea (66.1%), anemia (56.5%), neutrophil count decreased (54.8%), and vomiting (51.6%). No patients discontinued the treatment due to AEs.

Among 45 CLDN18.2 moderate to high patients (determined by a validated proprietary companion diagnostic kit) with measurable disease and at least one post-treatment tumor assessment in the 6 mg/kg dose- expansion phase, 36 (80.0%) patients achieved partial response and 9 (20.0%) achieved stable disease as the best overall tumor response per RECISTv1.1. Disease control rate was 100%. As of the cutoff date, 41(77.3%) out of the 53 patients in the dose expansion group were still on treatment.

In summary, ASKB589 plus CAPOX and PD-1 inhibitor as a first-line treatment in patients with G/GEJ cancer demonstrated good safety and tolerability. Adding a PD-1 inhibitor to ASKB589 plus CAPOX in patients with moderate to high CLDN18.2 expression resulted in encouraging anti-tumor activities with deep and durable responses. Based on the interim results of this study, NMPA greenlighted the Phase 3 study of ASKB589 in combination with CAPOX and PD-1 inhibitor as a first-line treatment in CLDN18.2 moderate to high (≥40% 2+/3+ staining) patients with advanced G/GEJ cancer in China.

Jian-Feng (Jeff) Lu, Ph.D., CEO of AskGene, commented: "Claudin 18.2 has recently been validated as a new molecular target that demonstrates clinical benefit for patients with gastric and gastroesophageal cancer. Our study shows that triple combination of ASKB589, chemotherapy, and PD-1 inhibitor can be administered safely in patients and results in a very high rate of deep and durable responses, as well as a 100% disease control rate. We have initiated the registrational trial and expect to enroll the first patient soon".

Presentation Details

Title: A Phase Ib/II Study of ASKB589 (Anti-CLDN18.2 Monoclonal Antibody) in Combination with CAPOX and PD-1 Inhibitor as a First-Line Treatment of Locally Advanced, Relapsed and Metastatic G/GEJ Cancer (NCT05632939)
Principle Investigator: Dr. Lin Shen, Peking University Cancer Hospital
Presenter: Dr. Zhi Peng, Peking University Cancer Hospital
Abstract #: 317
Poster #: E17
About NCT05632939

The NCT04632108 study is a Phase Ib/II, two-part, dose escalation and expansion study to evaluate the safety, tolerability, and anti-tumor activities of ASKB589 in combination with chemotherapy (CAPOX) and a PD-1 inhibitor as a first-Line treatment in patients with locally advanced, relapsed and metastatic G/GEJ cancer. The study includes ASKB589 dose escalation (6 and 10 mg/kg) and expansion study of ASKB589 (6 mg/kg) combined with CAPOX and PD-1 inhibitor. Patients with positive CLDN18.2 expression (any tumor cell with ≥1+ membrane staining) determined by the central lab have been enrolled.

About ASKB589

ASKB589 is an innovative biological drug discovered and developed by AskGene. It is a recombinant humanized monoclonal antibody targeting CLDN 18.2. The drug mediates antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) through high-affinity binding to CLDN18.2-expressing cancer cells. ASKB589 is intended for treatment of G/GEJ cancer, pancreatic cancer, and additional cancer types which express CLDN18.2.