On June 1, 2024 Ankyra Therapeutics, a clinical-stage oncology company developing anchored immunotherapies to improve the therapeutic window for immuno-oncology drugs, reported that it is presenting a Trial in Progress poster for the phase 1 ANCHOR clinical trial at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held May 31 – June 4, 2024 in Chicago, IL (Press release, Ankyra Therapeutics, JUN 1, 2024, https://www.businesswire.com/news/home/20240601270271/en/Ankyra-Therapeutics-Announces-Trial-in-Progress-Poster-Presentation-at-2024-ASCO-Meeting-and-Approval-of-ANK-101-Phase-1-Protocol-Amendment [SID1234643967]).

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Ankyra Therapeutics has developed an anchored drug-delivery platform based on linking immunotherapy drugs to aluminum hydroxide. The linked compounds are delivered locally to the tumor, where they are retained for several weeks promoting anti-tumor activity without systemic toxicity. Ankyra’s lead asset, ANK-101, is comprised of interleukin-12 with an alum-binding peptide that enables direct linkage with aluminum hydroxide. The ANCHOR study is a multi-institution, first-in-human, phase I clinical trial of ANK-101 in patients with superficially accessible solid tumors who have progressed after standard therapy was initiated in February 2024. The primary objectives of the study are to determine the safety, tolerability, and recommended dose of ANK-101 for further studies. The trial is active at five clinical study sites: Massachusetts General Hospital in Boston, MA; Providence Cancer Institute in Portland, OR; University of Pittsburgh in Pittsburgh, PA; Princess Margaret Hospital in Toronto, ON; and the National Cancer Institute (NCI), part of the National Institutes of Health, in Bethesda, MD. The poster presentation will include the rationale for the trial, study objectives, clinical trial design, and an update on accrual. The study will also evaluate pharmacokinetics, immune biomarkers, and quality of life.

In addition, Ankyra has received clearance from both the U.S. Food and Drug Administration (FDA) and Health Canada to amend the phase I clinical trial to include a second dose-escalation and expansion part to evaluate ANK-101 for injection into solid tumors located in visceral organs. This part will run concurrently with the current Phase I study with dosing to begin once patients in the superficial part have cleared a 21-day dose-limiting toxicity (DLT) observation period.

"We are delighted with the progress in the current phase I study which will help establish the initial safety profile and dosing selection for ANK-101," stated Howard L. Kaufman, MD, CEO of Ankyra Therapeutics. Dr. Kaufman also stated that "this study is the first step to realize the potential for anchored immunotherapy to deliver high doses of immunotherapy without systemic toxicity, which could represent an important advance in how we deliver effective cancer treatment in a safer manner." Joe Elassal, MD, Chief Medical Officer at Ankyra added "the recent approval to extend ANK-101 to visceral tumors is especially exciting as we can now study a broader patient population that could extend the potential indications for ANK-101 treatment".

For patients interested in enrolling in this clinical trial at NCI, please call NCI’s toll-free number: 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615); visit the website: View Source; and/or email: [email protected].

Title: A phase 1, open-label, dose escalation study on the safety and tolerability of ANK-101 in advanced solid tumors
Session Type: Poster Session
Session Title: Developmental Therapeutics – Immunotherapy
Track: Developmental Therapeutics – Immunotherapy
Sub Track: New Targets and New Technologies (IO)
Session Date and Time: Saturday June 1, 2024 9:00 AM CDT
Location: Hall A
Poster Board Number: 158a
Published Abstract Number: TPS2689
Citation: J Clin Oncol. 42, 2024 (suppl 16; abstr TPS2689)

The poster will be available on the publications section of Ankyra’s website after the meeting at View Source

About ANK-101

ANK-101 is an anchored drug complex composed of interleukin-12 (IL-12) linked to aluminum hydroxide. ANK-101 enables local delivery of functional IL-12 to the tumor microenvironment where it remains biologically active for several weeks but does not diffuse into the systemic circulation, thereby avoiding systemic toxicity. Treatment with ANK-101 in animal models has been associated with recruitment and retention of CD8+ T cells, NK cells and M1 macrophages activating innate and adaptive anti-tumor immunity. ANK-101 is being evaluated for the treatment of advanced solid tumors alone and in combination with anti-PD-1 agents. The Phase 1 first-in-human, open-label clinical trial of ANK-101 as a monotherapy (NCT:06171750) consists of a dose escalation portion that will evaluate the safety and tolerability of ANK-101, followed by dose expansion cohorts.

On June 1, 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 data of its novel drug candidate AGP-2449, a FAK/ALK/ROS1 tyrosine kinase inhibitor (TKI), in patients with non-small-cell lung cancer (NSCLC) 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 1, 2024, View Source;ascentage-pharma-releases-updated-data-of-fakalkros1-inhibitor-apg-2449-in-patients-with-nsclc-302161192.html [SID1234643948]). This is the third consecutive year in which clinical data from this study of APG-2449 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.

Results presented this year reaffirmed the therapeutic potential of APG-2449 in NSCLC, with data demonstrating preliminary efficacy in patients with NSCLC who were TKI naïve and resistant to second-generation ALK TKIs, as well as early antitumor activity in brain metastases. Biomarker analysis showed that, in patients with NSCLC resistant to second-generation ALK TKIs, phosphorylated FAK (pFAK) expression levels in tumor tissue at baseline and reduction in pFAK levels in peripheral blood mononuclear cells (PBMCs) were correlated with responses to APG-2449.

"APG-2449 is an effective multitargeted inhibitor that acts on FAK/ALK/ROS1. Compared to the data released at last year’s ASCO (Free ASCO Whitepaper) Annual Meeting, the latest results presented this year continued to show manageable safety and favorable antitumor activity in patients with NSCLC," said Prof. Li Zhang, the principal investigator of this study from Sun Yat-sen University Cancer Center. "We are very encouraged by the preliminary efficacy observed in patients with resistance to second-generation ALK TKIs, as it suggests that multitargeted inhibition on FAK and ALK may offer a new strategy for the management of patients with NSCLC resistant to second-generation ALK TKIs. We hope that Ascentage Pharma will conduct further studies on APG-2449 and allow more patients to benefit from this novel therapeutic agent as soon as possible."

"These data of APG-2449 in patients with NSCLC revealed a connection between resistance to ALK inhibitors and the FAK pathway, thus suggesting that the multitargeted FAK/ALK/ROS1 TKI APG-2449 may bring renewed hope to patients with NSCLC who are resistant to second-generation ALK inhibitors. This finding is indeed very encouraging," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "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 in need."

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

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.

Abstract#: 3124

Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Date and Time: June 1, 2024, Saturday, 9:00 AM – 12:00 PM (Central Time)

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

Highlights:

Background: ALK inhibitors increase FAK pathway gene expression in ALK+ NSCLC cell lines, with the highest induced expression in drug-tolerant persister cells. This suggests that FAK pathway activation is involved in the mechanism that leads to ALK TKI resistance in ALK+ NSCLC. APG-2449 is an orally active FAK inhibitor and a third-generation ALK/ROS1 TKI that has shown potent antitumor activity in preclinical models. This poster reports further safety and efficacy data of APG-2449.

Patient enrollment and methods:

This study comprises dose-escalation and dose-expansion portions. 1,200 mg daily (QD) was determined as the RP2D. There were two cohorts in the dose-expansion portion: Cohort 1 included patients with NSCLC who were resistant to second-generation ALK TKIs; Cohort 2 included patients with NSCLC who were ALK or ROS1 TKI naïve.
As of April 2, 2024, a total of 144 patients with NSCLC, mesothelioma, or ovarian cancer were treated with APG-2449 at doses ranging from 150 – 1,500 mg. The median (range) age of patients was 53 (21-78) years, and 53.5% were female.
Efficacy results:

The ORRs of APG-2449 in patients with ROS1+ and ALK+ TKI-naïve NSCLC (n=36) were 68.2% (15/22) and 78.6% (11/14), respectively. Of the 22 patients with NSCLC resistant to second-generation ALK inhibitors and without targetable bypass gene mutations (e.g., KRAS G12C, BRAF V600E), 10 achieved PRs (10/22; 45.5%). Among the patients treated at RP2D, 12 had brain metastasis at baseline, 9 of whom achieved intracranial PR, resulting in an intracranial ORR of 75.0%.
Biomarker analysis found that, in patients with NSCLC that was resistant to second-generation ALK TKIs, responses to APG-2449 were correlated with pFAK levels in tumor tissues at baseline and reductions in pFAK levels in PBMCs.
Safety results: A total of 129 (89.6%) patients had treatment‑related adverse events (TRAEs), the most frequent (≥10%) of which were elevated serum creatinine (49.3%), increase in alanine aminotransferase (42.4%), increase in aspartate aminotransferase (36.1%); nausea (28.5%); vomiting (23.6%); diarrhea (22.9%); decreased leukocyte count (22.2%), decreased neutrophil count (17.4%) and rash (13.2%). In all, 20 (13.9%) TRAEs were grade ≥ 3.

Conclusions: APG-2449 demonstrated preliminary efficacy in patients with NSCLC whose disease was TKI naïve and resistant to second-generation ALK inhibitors, especially in brain metastases. Biomarker analysis showed that, in patients with NSCLC resistant to second-generation ALK TKIs, responses to APG-2449 PFS were correlated with pFAK levels in tumor tissues at baseline and reductions in pFAK levels in PBMCs.

*APG-2449 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
withtyrosinekinase inhibitor (TKI)-
resistantsuccinatedehydrogenas
e (SDH)-deficientgastrointestinal
stromal tumor (GIST)and
paraganglioma

#11502

Oral
Report

Lisaftoclax
(APG-2575）

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

#6541

Poster
Presentation

Updated efficacy and safety results of
BCL-2 inhibitorlisaftoclax (APG-2575)
alone or combinedwithibrutinibor
rituximab in patients (pts)with
Waldenströmmacroglobulinemia
(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 tosecond-
generationALK inhibitors

#3124

Poster
Presentation

On June 1, 2024 Nuvation Bio Inc. (NYSE: NUVB), a late clinical-stage, global biopharmaceutical company tackling some of the greatest unmet needs in oncology, reported that results from the pivotal Phase 2 TRUST-I study conducted in China evaluating taletrectinib, its investigational 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, taking place in Chicago, Illinois (Press release, Nuvation Bio, JUN 1, 2024, View Source [SID1234643968]).

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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 tumors shrank (confirmed objective response rate, cORR, as assessed by an independent review committee, IRC) in 91% of taletrectinib-treated patients who had not previously been treated with a ROS1 TKI (ROS1 TKI-naïve) and 52% of taletrectinib-treated 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).

"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 signal and favorable safety profile, underscoring its potential to become a new treatment option for patients."

"TRUST-I is one of the largest prospective trials conducted to date in ROS1-positive NSCLC. We now have data with long-term follow-up and are very pleased that results remain highly consistent with previously reported taletrectinib data, demonstrating its best-in-class potential," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "We look forward to further advancing taletrectinib and plan to share results from the global, pivotal TRUST-II study by the end of 2024, as we aim to become a commercial-stage organization by the end of 2025."

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 had either 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. 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 following treatment with taletrectinib (cORR).
Brain tumors shrank in 87.5% of taletrectinib-treated patients 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 following treatment with taletrectinib were still responding, and 70.5% of patients were still progression-free.
In TKI-pretreated patients (n=66):

51.5% of patients’ tumors shrank following treatment with taletrectinib (cORR).
Brain tumors shrank in 73.3% of taletrectinib-treated patients who had measurable central nervous system tumors (n=15; intracranial cORR).
Tumors shrank in 66.7% of taletrectinib-treated 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 following treatment with taletrectinib 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, "Efficacy and Safety of Taletrectinib in Patients with Advanced or Metastatic ROS1+ Non-Small Cell Lung Cancer: The Phase 2 TRUST-I Study," (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, and will be made available on Nuvation Bio’s website at www.nuvationbio.com/publications.

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, AnHeart Therapeutics Ltd., a Nuvation Bio company, entered into an exclusive license agreement with Innovent Biologics, Inc. for the co-development and commercialization of taletrectinib in Greater China, including mainland China, Hong Kong, Macau, and Taiwan.

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.

On June 1, 2024 Jacobio Pharma (1167.HK), a clinical-stage oncology company focusing on undruggable targets, reported updated data of a KRAS G12C inhibitor glecirasib (JAB-21822) in combination with a SHP2 inhibitor (JAB-3312) in frontline non-small cell lung cancer (NSCLC) patients harboring KRAS G12C mutation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting as form of oral presentation (Press release, Jacobio Pharmaceuticals, JUN 1, 2024, View Source [SID1234643949]). Jacobio also presented updated data of pivotal phase II study of glecirasib as form of oral presentation at an education session.

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As of April 7, 2024, 194 patients participated in a phase II trial of using glecirasib combined with JAB-3312 (NCT05288205), of which 102 patients were frontline NSCLC. The median follow-up time was 10.1 months.

In the oral abstract session (Abstract No. 3008), Professor Jun Zhao, chief physician of Beijing Cancer Hospital, the principal investigator of glecirasib combined with JAB-3312 study, presented the clinical data. About 102 frontline NSCLC patients have been enrolled in 7 dose groups. The confirmed objective response rate (cORR) was 64.7% (66/102), the disease control rate (DCR) was 93.1% (95/102), and the median progression-free survival (mPFS) was 12.2 months, respectively.

This trial explored a total of 7 different dose cohorts, and the optimal dose group was glecirasib at 800mg daily combined with JAB-3312 at 2mg daily one week on and one week off. The cORR of the optimal dose group was 77.4% (18/31), and 54.8% (17/31) of patients achieved a deep response with tumors shrinking by more than 50%. The mPFS was not yet mature.

Regarding on the safety data, among the 194 patients, the incidence of grade 3 or 4 treatment-related adverse events (TRAE) was 43.8%, and there was no treatment-related death. Common TRAEs treatment-related adverse events include anemia, hypertriglyceridemia, etc. The safety profile in the frontline NSCLC is similar to that of the overall study population, and the overall safety is manageable.

Professor Jie Wang, chief physician of Beijing Cancer Hospital, commented, "from the above data, it can be seen that the combination therapy of glecirasib and JAB-3312 has a good safety profile, and the efficacy data shows positive therapeutic potential. If the combination of the two oral drugs can show superiority to the existing standard therapy (immunotherapy combined with chemotherapy) in subsequent trials, we anticipate that patients can avoid the side effects of chemotherapy or immunotherapy."

The combination therapy of glecirasib and JAB-3312 is being tested in a Phase III clinical trial of frontline NSCLC with KRAS G12C mutation in China. Andrea Gillam-Wang M.D., Ph.D., Chief Medical Officer and Global Head of R&D of Jacobio, said: "Our R&D efforts have been focusing on patient needs. We look forward to testing this novel combination against standard care chemotherapy and immunotherapy in NSCLC, and potentially replace standard care regimen consisted of multiple intravenous agents with two oral agents."

The new drug application (NDA) of glecirasib monotherapy for the second-line NSCLC with KRAS G12C mutation was granted Priority Review designation by China CDE on May 21, 2024 In the education session of ASCO (Free ASCO Whitepaper), Professor Yuankai Shi, chief physician of Cancer Hospital Chinese Academy of Medical Sciences, updated the data of the Phase II registration trial of NSCLC with KRAS G12C mutation in an oral report.

Jacobio Pharma will hold a data discussion call at 20:00 Beijing time on June 3. Please click the link to register: View Source

About Glecirasib
Glecirasib is a KRAS G12C inhibitor developed by Jacobio. A number of Phase I/II clinical trials of glecirasib are currently ongoing in China, the United States and Europe for patients with advanced solid tumors harboring KRAS G12C mutation. These include combination therapy trials with SHP2 inhibitor JAB-3312 in NSCLC and with cetuximab in colorectal cancer. The pancreatic cancer indication has obtained orphan drug designation in the United States and breakthrough therapy designation in China.

About JAB-3312
JAB-3312 is a highly selective SHP2 allosteric inhibitor with best-in-class potential. Jacobio is currently conducting clinical trials of JAB-3312 in monotherapy and combination therapies with glecirasib and other agents in China, the United States and Europe. The phase III study in combination with KRAS G12C inhibitor Glecirasib has been approved by China CDE in Feb 2024.

On June 1, 2024 Accutar Biotechnology, Inc., a biotechnology company focusing on artificial intelligence (AI)-enabled drug discovery, reported data from an ongoing Phase 1 study of AC699 monotherapy in patients with ER-positive / HER2-negative locally advanced or metastatic breast cancer (Press release, Accutar Biotechnology, JUN 1, 2024, View Source;Breast-Cancer-at-ASCO-2024 [SID1234643969]). The data will be presented in a poster discussion session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL on June 1, 2024.

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AC699 is a potent and selective orally bioavailable, chimeric degrader of estrogen receptor (ER) α, and offers a potential new breast cancer treatment option based on a differentiated mechanism of action as compared to fulvestrant and novel SERDs with deeper ERα degradation as demonstrated in preclinical studies. AC699 is currently being evaluated in an ongoing Phase 1 clinical study as a single agent for the treatment of ER-positive / HER2-negative locally advanced or metastatic breast cancer (NCT05654532). The primary objectives are to evaluate the safety and tolerability of AC699. Secondary and exploratory objectives include pharmacokinetics, preliminary efficacy and pharmacodynamic evaluation. The study uses a 3+3 dose-escalation design, with once-daily oral dosing of AC699 at 100, 200, 300, 400, and 600 mg.

Phase 1 Study Results:

As of April 8, 2024, 29 participants were enrolled and treated with AC699 at doses ranging from 100-400 mg. The participants had a median of 5 (range 2-10) prior lines of therapy, including 3 (range 1-8) prior lines in the metastatic setting
The objective response rate was 21% (4/19) and increased to 50% (4/8) for those who had an ESR1 mutation
There were no > Grade 3 drug-related adverse events (AEs), no dose limiting toxicities, no discontinuations and no dose reductions due to AEs
AEs related to AC699 occurred in 38% of participants and included nausea (14%), hot flush (14%), and fatigue (10%)
The maximum tolerated dose had not been reached yet
Details of the poster presentation at ASCO (Free ASCO Whitepaper) 2024 are as follows:

Date/Time: June 1, 2024, 9:00 AM – 12:00 PM CDT
Abstract Number: 3074
Title: Preliminary results from a phase 1 study of AC699, an orally bioavailable chimeric estrogen receptor degrader, in patients with advanced or metastatic breast cancer.
Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Abstracts and full session details can be accessed through the ASCO (Free ASCO Whitepaper) meeting planner: Link
"We are extremely pleased with the groundbreaking safety and efficacy that AC699 has demonstrated thus far in Phase 1, with early evidence of its best-in-class potential, especially for patients with ESR1 mutations," said Jie Fan, Ph.D., Chief Executive Officer of Accutar Biotechnology, Inc. "We look forward to completing the dose escalation portion of the study and starting the Phase 2 study soon. We believe that the oral dosing of AC699 and its differentiated mechanism of action, as compared to fulvestrant and novel SERDs, can potentially provide a new safe and effective treatment option for this patient population."

About AC699 and the Phase 1 Study (AC699-001)

AC699 is an investigational orally bioavailable, chimeric degrader of estrogen receptor (ER) α. In preclinical studies, AC699 has demonstrated potent and selective protein degradation of ERα wildtype and mutants with favorable pharmacological properties, as well as promising anti-tumor activities in ER-positive animal tumor models.

The purpose of the Phase 1 multi-center, open-label study is to assess the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of AC699 treatment in patients with ER-positive / HER2-negative locally advanced or metastatic breast cancer (NCT05654532). Additional information on this clinical trial can be found on www.clinicaltrials.gov.