On June 4, 2024 AbelZeta Pharma, Inc. ("AbelZeta" or the "Company"), a global clinical-stage biopharmaceutical company focused on the discovery and development of innovative and proprietary cell-based therapeutic products, reported preliminary safety and efficacy results from its first time in human investigator-initiated trial (IIT) of C-CAR031 in connection with the Company’s oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, AbelZeta, JUN 4, 2024, View Source [SID1234644103]). The presentation shared data indicating a manageable safety profile and encouraging anti-tumor activity of C-CAR031 in patients with heavily pretreated advanced hepatocellular carcinoma (HCC) (1-6 lines of prior therapy). C-CAR031 is based on a novel GPC3-targeting CAR-T designed by AstraZeneca (LSE/STO/Nasdaq: AZN) and is manufactured by AbelZeta. C-CAR031 is being co-developed in China by AbelZeta and AstraZeneca.

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"We are encouraged by the first clinical results of C-CAR031 in advanced hepatocellular carcinoma (HCC) patients," said Tony (Bizuo) Liu, Chairman and CEO of AbelZeta. "The early data presented today provide compelling proof-of-concept to potentially redefine therapeutic paradigms in HCC and other GPC3-expressing solid tumors."

Principal Investigator (PI) of the study, Professor Tingbo Liang from the First Affiliated Hospital of Zhejiang University, stated "C-CAR031 showed a good safety profile and promising efficacy in late-stage hepatocellular carcinoma patients, who typically have a limited number of treatment options available. The observed tumor shrinkage in the large/vast majority (91.3%) of the patients suggests that C-CAR031 has the potential to bring clinical value and offer hope to these patients."

As of March 14, 2024, 23 of 24 patients on the study were eligible for efficacy assessment. Tumor reductions were observed in 91.3% patients, in both intrahepatic and extrahepatic lesions, with a median reduction of 42.2% (range, -28.1% 94.4%). The disease control rate was 91.3% and the ORR was 56.5% for patients across all DLs. In DL4, the ORR was 75.0%. With 9.03-month median follow-up, Kaplan-Meier estimation of median overall survival (mOS) is 11.14 months (95% CI, 7.56-NE).

No dose-limiting toxicity or immune effector cell associated neurotoxicity syndrome (ICANS) was observed. Cytokine release syndrome (CRS) was observed in 22 (91.7%) patients with the majority (87.5%) grade 1/2 CRS and only 1 (4.2%) grade 3 CRS.

About C-CAR031

C-CAR031 is an autologous, armored GPC3-targeting chimeric antigen receptor T-Cell (CAR-T) therapy, being studied for the treatment of HCC. It is based on a novel GPC3-targeting CAR-T designed by AstraZeneca using their dominant negative transforming growth factor-beta receptor II dominant negative (dnTGFβRII) armoring discovery platform and is manufactured by AbelZeta in China. C-CAR031 is being developed in China under a co-development agreement between AbelZeta and AstraZeneca.1

About the Study

A Phase I clinical study (NCT05155189) aiming to assess the safety and anti-tumor activity of C-CAR031 injection in advanced/unresectable HCC patients is being conducted in China. As of March 14, 2024, a total of 24 patients received C-CAR031 infusion at 4 dose levels (DLs). 83.3% (20/24) had extrahepatic metastasis. The median number of prior lines of systemic therapy was 3.5 (range 1-6).

Abstract Title: "Phase I study of C-CAR031, a GPC3-specific TGFβRIIDN armored autologous CAR-T, in patients with advanced hepatocellular carcinoma (HCC)."
Abstract Number: 4019
Session Type and Title: Rapid Oral Abstract – Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary
Session Date and Time: 6/3/2024; 9:45 AM-11:15 AM CDT

On June 4, 2024 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that the final follow-up results of the investigator-initiated trial CT041-CG4006 (NCT03874897) of satricabtagene autoleucel ("satri-cel", CT041) (an autologous CAR T-cell product candidate against Claudin18.2) have been published in Nature Medicine on June 3, 2024. Data were presented as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting on June 3, 2024, 12:30 pm-3:30 pm, Eastern Daylight Time (Press release, Carsgen Therapeutics, JUN 4, 2024, View Source [SID1234644102]). Further details have been posted on the corporate website View Source

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The article in Nature Medicine was titled "Claudin18.2-specific CAR T Cells in gastrointestinal cancers: phase 1 trial final results".[1]

The 2024 ASCO (Free ASCO Whitepaper) Annual Meeting abstract was titled "Claudin18.2-Targeted Chimeric Antigen Receptor T Cell Therapy for Patients with Gastrointestinal Cancers: Final Results of CT041-CG4006 Phase 1 Trial".[2]

The leading PI of this study, Professor Lin Shen of Beijing Cancer Hospital, said, "Satri-cel has shown promising efficacy and manageable safety profiles in patients with Claudin18.2-positive advanced gastrointestinal cancers, particularly those with gastric cancer or gastroesophageal junction cancer. This study marks a significant advancement in the field of CAR T-cell therapy for solid tumors. It suggests that CAR T-cell therapy has the potential to transform existing treatment paradigms and provides important reference points for further innovative research. In the future, we anticipate that more clinical trials and studies will further validate and refine this innovative therapy, enabling it to benefit a broader patient population as soon as possible."

Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics, said, "We are delighted to announce that the final results of the CT041-CG4006 study have been simultaneously published in the prestigious journal Nature Medicine and reported as an oral presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting. This study represents a significant milestone in the field of CAR T-cell therapy for solid tumors, demonstrating the encouraging safety and efficacy of satri-cel. We extend our heartfelt thanks to the investigators for their years of dedicated efforts, and to the patients and their families for their trust and support. It is our shared goal to provide better treatment options for patients, and we will continue to advance the global clinical development of satri-cel, ensuring this innovative CAR T-cell therapy benefits more patients with gastric, pancreatic, and other gastrointestinal cancers."

About Satri-cel

Satri-cel is an autologous CAR T-cell product candidate against the protein Claudin18.2 that can potentially be the first-in-class globally. Satri-cel has been developed for the treatment of Claudin18.2 positive solid tumors with a primary focus on gastric cancer/gastroesophageal junction cancer (GC/GEJ) and pancreatic cancer (PC). Ongoing trials include investigator-initiated trials (CT041-CG4006, NCT03874897), a confirmatory Phase II clinical trial for advanced GC/GEJ in China (CT041-ST-01, NCT04581473), a Phase I clinical trial for PC adjuvant therapy in China (CT041-ST-05, NCT05911217), and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02, NCT04404595). Satri-cel was granted Regenerative Medicine Advanced Therapy (RMAT) designation by the U.S. FDA for the treatment of advanced GC/GEJ with Claudin18.2-positive tumors in January 2022 and was granted PRIME eligibility by the EMA for the treatment of advanced gastric cancer in November 2021. Satri-cel received an Orphan Drug designation from the U.S. FDA in 2020 for the treatment of GC/GEJ and an Orphan Medicinal Product designation from the EMA in 2021 for the treatment of advanced gastric cancer.

On June 4, 2024 SciTech Development, a clinical-stage, specialty oncology pharmaceutical company, reported it has closed an additional $3.2 million in funding to continue the active enrollment and dosing of patients in its ongoing clinical trial for T-cell non-Hodgkin lymphoma (T-NHL) (Press release, SciTech Development, JUN 4, 2024, View Source [SID1234644101]).

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This new funding brings SciTech’s total raised to over $12 million. SciTech’s financing was led by Storm Lake Capital and Pointe Angels, alongside new and existing accredited investors. Proceeds from the financing will be used to advance the company’s Phase 1b clinical trials of ST-001 for T-NHL and subsequent clinical trials for small cell lung cancer.

"On behalf of Storm Lake Capital, we are thrilled with the initial clinical progress made by SciTech Development and pleased to further support the company through additional investment in its latest convertible note round." said Todd Carlson, Partner, Storm Lake Capital. "As early supporters, we have closely monitored SciTech’s advancements, noting its adept handling of challenges and disciplined resource management. We value the management team’s integrity and look forward to their continued success."

SciTech’s T-NHL trial began with the first patient dosed in late 2023 and is being conducted at six (6) prestigious cancer institutions located across the United States in PA, NY, TX, MI, and CA, with additional sites being added. Patient enrollment is now open. Trial information, including criteria and site locations, can be found at ClinicalTrials.gov with the identifier NCT04234048. SciTech anticipates starting a second Phase 1b small cell lung cancer (SCLC) trial to run concurrently with the T-cell lymphoma trial.

"SciTech has achieved yet another milestone of having oversubscribed its second Convertible Note Round (CNR) of financing. This is a perfect reflection of the progress that has been made by our dedicated team. Our multicenter clinical trial is to reconfirm the safety and efficacy of the active drug, fenretinide, utilizing SciTech’s novel nanoparticle delivery platform." said Earle Holsapple, CEO of SciTech. "We have opened a third CNR to continue advancing the Phase 1b studies for T-NHL and small cell lung cancer. In parallel, the company will launch a Series A capital raise to fund the completion of both trials and file for commercial approval with the FDA. We are confident that the drug’s potential will soon be realized."

ST-001 is SciTech’s patented lead drug product, formulated with the active drug fenretinide (a synthetic retinoid derivative) plus specific phospholipids in a nanoparticalized delivery platform (SDP). ST-001 has achieved a breakthrough in solving the bioavailability issues of fenretinide without system-related toxicities, which allows the drug to reach and kill cancer cells. The FDA has granted ST-001 an Orphan Drug Designation, allowing 7 years of market exclusivity once approved.

T-cell lymphoma, a rare disease, is being utilized as the initial gateway indication for ST-001 as the company plans to establish a foothold in other cancer indications. Previous studies with fenretinide have shown promise in at least 15+ other types of cancers, such as lung, breast, ovarian, cervical, pancreatic, leukemia, colo-rectal, head & neck, and brain cancers. These additional indications, plus the potential to add ST-001 as combination therapy, may add significant value to address the unmet clinical needs in oncology.

On June 4, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that it has released updated results from a global, multicenter Phase Ib/II study of the Bcl-2 inhibitor lisaftoclax (APG-2575) alone or in combinations for the treatment of patients with Waldenström macroglobulinemia (WM), in a poster presentation at the 60th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, IL (Press release, Ascentage Pharma, JUN 4, 2024, View Source;ascentage-pharma-releases-updated-data-showing-promising-efficacy-and-safety-of-lisaftoclax-in-patients-with-wm-302164161.html [SID1234644100]). This is the second consecutive year in which this study of lisaftoclax, a key drug candidate in the company’s apoptosis-targeted pipeline, was selected for presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting.

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The ASCO (Free ASCO Whitepaper) Annual Meeting showcases the most cutting-edge research in clinical oncology and state-of-the-art advanced cancer therapies and is the world’s most influential and prominent scientific gathering of the clinical oncology community. Presenting clinical development progress at the ASCO (Free ASCO Whitepaper) Annual Meeting for the seventh consecutive year, Ascentage had four clinical studies of three of the company’s proprietary drug candidates selected for presentations, including an oral report, at ASCO (Free ASCO Whitepaper) 2024.

The latest results from this clinical study validated the favorable safety and efficacy of lisaftoclax monotherapy and in combinations in WM. According to the data, lisaftoclax combined with ibrutinib showed an objective response rate (ORR) of 90.9% in treatment-naïve patients with WM (responses that were unaffected by the CXCR4 mutation), manageable adverse events (AEs), and a low risk of tumor lysis syndrome (TLS). In addition, no potential drug-drug interactions (DDIs) with ibrutinib were observed in the study.

"Lisaftoclax is a novel Bcl-2 selective inhibitor developed to treat malignancies by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells," said Dr. Sikander Ailawadhi, the Principal Investigator of the Study from Mayo Clinic. "In this global Phase Ib/II study in patients with relapsed/refractory (R/R) WM, lisaftoclax both as a monotherapy and in combination with ibrutinib or rituximab has shown favorable efficacy that was not negatively affected by the presence of the CXCR4 mutation. In addition, lisaftoclax showed a manageable safety profile with low risk of TLS during daily dose ramp-up. We look forward to seeing more data from this trial."

"Lisaftoclax is the first pivotal-stage Bcl-2 inhibitor in China and the second globally that has demonstrated promising efficacy," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "The updated clinical data of lisaftoclax in WM presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting underscore the drug’s strong therapeutic potential, both as a monotherapy and in combinations, for the treatment of hematologic malignancies. We will continue to advance the clinical development of lisaftoclax with the hope to allow more patients to benefit from the drug as soon as possible."

Highlights of these data presented at ASCO (Free ASCO Whitepaper) 2024 are as follows:

Updated efficacy and safety results of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM)

Abstract#: 7078

Session Title: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia

Date and Time: June 3, 2024, Monday, 9:00 AM– 12:00 PM (Central Time)

First Author: Masa Lasica, MBBS, FRACP, FRCPA, St Vincent’s Hospital, Melbourne, Victoria, Australia.

Highlights:

Background: Lisaftoclax is a novel, oral, highly selective, potent Bcl-2 inhibitor. In an ibrutinib-resistant patient-derived WM xenograft/preclinical model, lisaftoclax combined with ibrutinib has a strong synergistic effect.

Introduction: This was an open-label, multicenter, global Phase Ib/II study designed to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of lisaftoclax monotherapy or in combinations with agents such as ibrutinib/rituximab in patients with WM.

Patient enrollment and methods:

In this study, patients with WM were enrolled in 3 arms, including Arm A: lisaftoclax monotherapy in patients resistant to or intolerant of prior treatment with Bruton’s tyrosine kinase inhibitors (BTKis); Arm B: lisaftoclax combined with ibrutinib in treatment-naïve patients with WM; and Arm C: lisaftoclax combined with rituximab in BTKi-naïve patients with relapsed/refractory WM.
Lisaftoclax was orally administered once daily in 28-day cycles. Lisaftoclax was gradually escalated from the starting dose of 400 mg to 1,200 mg. As of January 25, 2024, a total of 46 patients were enrolled in the study (Arm A [n=14] at doses of up to 1,000 mg; Arm B [n=24] at doses of up to 1,200 mg; Arm C [n=8] at doses of up to 800 mg).
Efficacy results:

The median (range) durations of treatment were 11 (1-28), 23.5 (1-34), and 11.5 (5-33) months for Arms A, B, and C, respectively.
The ORRs (PR, very good partial response [VGPR], CR) were 41.7%, 90.9%, and 37.5% for Arms A, B, and C, respectively.
In Arm A, patients with wild-type CXCR4 (n =7) had better overall responses to lisaftoclax than the CXCR4 mutation group (n = 3).
In Arms B and C, no significant differences between patients with/without CXCR4 mutation were observed.
Safety results:

In Arm B, 1 dose-limiting toxicity (DLT, grade 3 clinical TLS), in the setting of anticipated renal impairment, occurred at 1,200 mg; and 1 grade 3 laboratory TLS, primarily attributed to dehydration and concomitant symptomatic therapies, occurred at 1,000 mg. Abnormal electrolytes was resolved without recurrence after 1 day of drug interruption.
Grade ≥ 3 lisaftoclax-related AEs included neutropenia (15.2%), thrombocytopenia (4.3%), decreased leukocytes (4.3%), TLS (4.3%), anemia (2.2%), weight loss (2.2%), and septic shock (2.2% in the setting of neutropenia).
Ventricular arrhythmia was not observed.
One patient required dose reduction because of neutropenia.
The maximum-tolerated dose (MTD) was not reached.
Lisaftoclax combined with ibrutinib showed a PK exposure comparable to lisaftoclax or ibrutinib alone, indicating no potential DDIs.
Conclusions: Lisaftoclax alone or combined with ibrutinib or rituximab was well tolerated and demonstrated measurable effects in patients with treatment-naïve or BTKi-treatment-failed WM.

*Lisaftoclax is an investigational drug that has not been approved in any country and region.

Appendix: The four clinical studies of Ascentage Pharma’s three drug candidates, including lisaftoclax, presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting.

Drug Candidates

Abstract Title

Abstract#

Format

Olverembatinib
(HQP1351)

Updated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) and paraganglioma.

#11502

Oral

Report

Lisaftoclax

(APG-2575)

Safety and efficacy of lisaftoclax, a novel BCL-2 inhibitor, in combination with azacitidine in patients with treatment-naïve or relapsed or refractory acute myeloid leukemia.

#6541

Poster
Presentation

Updated efficacy and safety results of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM).

#7078

Poster
Presentation

APG-2449

Updated study results of novel FAK/ALK/ROS1 inhibitor APG-2449 in patients (pts) with non-small-cell lung cancer (NSCLC) resistant to second-generation ALK inhibitors.

On June 4, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that it has released updated clinical data of olverembatinib (HQP1351), a third-generation tyrosine kinase inhibitor (TKI), in patients with TKI-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST), in an oral report at the 60th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, IL (Press release, Ascentage Pharma, JUN 4, 2024, View Source;oral-report-released-latest-data-of-olverembatinib-in-sdh-deficient-gist-including-a-cbr-of-92-3-302164178.html [SID1234644099]). This is the third consecutive year in which clinical data from this study of olverembatinib were selected for presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting.

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The ASCO (Free ASCO Whitepaper) Annual Meeting showcases the most cutting-edge research in clinical oncology and state-of-the-art advanced cancer therapies and is the world’s most influential and prominent scientific gathering of the clinical oncology community. Presenting clinical development progress at the ASCO (Free ASCO Whitepaper) Annual Meeting for the seventh consecutive year, Ascentage had four clinical studies of three of the company’s proprietary drug candidates selected for presentations, including an oral report, at ASCO (Free ASCO Whitepaper) 2024.

The oral report features the latest data that further validated the promising efficacy and manageable safety of olverembatinib in SDH-deficient GIST. The Phase I study enrolled a total of 26 patients with SDH-deficient GIST. Among these patients, 6 achieved partial responses (PR), 18 achieved stable diseases (SD) that lasted longer than four treatment cycles, with a clinical benefit rate (CBR) of 92.3% (24/26) and a median progression-free survival (PFS) of 25.7 months.

Olverembatinib, an orally-available novel TKI developed by Ascentage Pharma, is the first third-generation BCR-ABL inhibitor approved in China. At present, the drug is approved in China in two indications, including adult patients with TKI-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation; and adult patients with CML-CP resistant to and/or intolerant of first-and second-generation TKIs. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics.

While being clinically developed and adopted for the treatment of hematologic malignancies, olverembatinib is also being clinically evaluated in patients with GIST. To date, olverembatinib has been granted a Breakthrough Therapy Designation by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for the treatment of patients with SDH-deficient GIST who had received first-line treatment.

"SDH-deficient GIST represents a treatment gap that urgently needs new treatment options," said Prof. Haibo Qiu, of Sun Yat-Sen University Cancer Center, and the presenter of the report. "In the study, olverembatinib has shown impressive clinical benefits in SDH-deficient GIST, including a median PFS of 25.7 months, as well as favorable safety and tolerability profiles. Moving forward, we will continue to evaluate the drug’s efficacy and safety in SDH-deficient GIST."

"Building on data released at the ASCO (Free ASCO Whitepaper) Annual Meeting in the past two years, results presented in the oral report this year continued to demonstrate promising clinical benefits and manageable safety of olverembatinib in SDH-deficient GIST," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "We are very encouraged by these results, as they signal a potential breakthrough in addressing another indication with an urgent unmet clinical need. Remaining committed to the mission of addressing unmet clinical needs in China and around the world, we will press forward with this clinical development program in order to bring a safe and effective new treatment option to patients as soon as possible."

Highlights of these data presented at ASCO (Free ASCO Whitepaper) 2024 are as follows:

Updated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST)

Abstract#: 11502

Session Title: Sarcoma

Date and Time: June 3, 2024, Monday, 3:00 PM – 6:00 PM (Central Time)

First Author: Haibo Qiu, MD, PhD, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

Highlights:

Background: SDH-deficient GIST is a subset of wild-type GIST that constitutes approximately 10% of GISTs. In the National Comprehensive Cancer Network (NCCN) guidelines, there is no preferred regimen for SDH-deficient GIST, thus indicating an urgent unmet medical need. Olverembatinib, approved in China for the treatment of patients with chronic myeloid leukemia, has shown promising clinical efficacy in SDH-deficient GIST. In this abstract, the study reports updated efficacy data of olverembatinib in SDH-deficient GIST.

Introduction: The aim of this study was to evaluate the safety and efficacy (per RECIST v1.1) of olverembatinib in patients with SDH-deficient GIST and other solid tumors. Olverembatinib was administered orally once every other day (QOD) in 28-day cycles.

Patient enrollment and methods: As of December 27, 2023, 26 patients with SDH-deficient GIST (confirmed by immunohistochemistry [IHC] assay) had received ≥1 dose of olverembatinib (median [range] age, 30 [13-56] years), and 25 of them had received 1-4 tyrosine kinase inhibitors (TKIs; 50.0%% [13/26] of patients received ≥3 TKIs). Olverembatinib was administered OQD in doses ranging from 30 to 50 mg (30 mg [n = 6]; 40 mg [n = 14]; 50 mg [n = 6]).

Efficacy Results: In the 26 patients with SDH-deficient GIST, the median (range) duration of treatment was 15.6 (1.8-42.3) months. 6 of these patients achieved partial responses (PR); and another 18 patients achieved stable diseases (SD) lasting > 4 cycles. The clinical benefit rate (CBR, complete response [CR] + PR + SD > 4 cycles) was 92.3% (24/26), the longest treatment duration was 40 months, and the median (range) PFS was 25.7 months (12.9-not reached [NR]).

Safety results: The adverse event profile was the same as previously reported (Qiu H, et al, J Clin Oncol 41:11540), with no newly emergent safety issues observed.

Conclusions: Olverembatinib was well tolerated. In patients with SDH-deficient GIST, olverembatinib demonstrated a CBR exceeding 90% and significantly prolonged the estimated median PFS, indicating the potential benefit of this treatment and providing a benchmark for future studies in this rare subtype of GIST.

*Olverembatinib is an investigational drug that has not been approved for any indication outside the Chinese mainland.

Appendix: The four clinical studies of Ascentage Pharma’s three drug candidates, including lisaftoclax, presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting.

Drug Candidates

Abstract Title

Abstract#

Format

Olverembatinib (HQP1351)

Updated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) and paraganglioma.

#11502

Oral

Report

Lisaftoclax

（APG-2575）

Safety and efficacy of lisaftoclax, a novel BCL-2 inhibitor, in combination with azacitidine in patients with treatment-naïve or relapsed or refractory acute myeloid leukemia.

#6541

Poster Presentation

Updated efficacy and safety results of BCL-2 inhibitor lisaftoclax (APG-2575) alone or combined with ibrutinib or rituximab in patients (pts) with Waldenström macroglobulinemia (WM).

#7078

Poster Presentation

APG-2449

Updated study results of novel FAK/ALK/ROS1 inhibitor APG-2449 in patients (pts) with non-small-cell lung cancer (NSCLC) resistant to second-generation ALK inhibitors.

#3124

Poster Presentation