On September 16, 2024 Akeso (9926.HK) reported the phase 2 results from its ivonescimab in combination with chemotherapy as a first-line (1L) treatment for triple-negative breast cancer (TNBC) at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Conference (Press release, Akeso Biopharma, SEP 16, 2024, View Source [SID1234646678]). The preliminary data, with only a 10-month median follow-up, revealed that the ivonescimab combination regimen demonstrated excellent efficacy and a favorable safety profile in 1L TNBC. Professor Wang Xiaojia from Zhejiang Provincial Cancer Hospital, a co-primary investigator of the study, presented the findings orally at the conference.

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As of May 31, 2024, a total of 30 patients with locally advanced unresectable or metastatic TNBC were enrolled. 80% of patients had a PD-L1 combined positive score (CPS) <10, and 60% of patients had previously received taxane-based neoadjuvant or adjuvant therapy (a proportion higher than that observed in similar studies involving targeted drugs).

Although the follow-up period is relatively short and the data are not yet mature, the study still demonstrates that the ivonescimab combination regimen demonstrates excellent progression-free survival (PFS) benefits for TNBC patients, with safety consistent with previous ivonescimab-related studies.

Ivonescimab combination regimen demonstrated high efficacy in tumor response and disease control, with an objective response rate (ORR) of 72.4% and a disease control rate (DCR) of 100%, including a complete response (CR) rate of 6.9%.
As of the latest update, five additional patients have achieved partial response (PR) (Among them, four newly evaluable patients all achieved a PR, and one patient who previouly had stable disease also achieved a PR ), leading to an adjusted ORR of approximately 78.8% and DCR of 100%.
Ivonescimab combination regimen showed a promising trend towards improved long-term survival benefits, with a median progression-free survival (PFS) of 9.3 months (6.24 months -NE), and a 6-month PFS rate of 73.3%.
In the PD-L1 CPS≥10 population, the ORR was 83.3%, and the median PFS was not yet reached.
In the PD-L1 CPS <1 population, the ORR was 86.7%, with a median PFS of 9.3 months (5.26 months-NE).
As of the latest update, two additional patients in the PD-L1 CPS <1 group have achieved PR, resulting in an adjusted ORR of 88.2%.
In the PD-L1 CPS <10 population, the ORR was 69.6%, with a median PFS of 9.3 months (5.55 months-NE).
As of the latest update, five additional patients in this group have achieved PR, leading to an adjusted ORR of approximately 77.8%.
Ivonescimab combined with chemotherapy as a first-line treatment for TNBC exhibited an acceptable safety profile. The most common treatment-related adverse events (TRAEs) were predominantly grade 1-2 and manageable, consistent with previous studies. There were no TRAEs that led to permanent treatment discontinuation or death.

On September 16, 2024 MEDSIR, a leading company dedicated to promoting independent clinical research in oncology internationally and part of Oncoclinicas & Co, the largest hospital group dedicated to cancer treatment in Latin America, reported this year in the congress of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper), held in Barcelona, presenting 12 new studies addressing different types of cancer (Press release, MedSIR, SEP 16, 2024, View Source [SID1234646677]).

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The studies presented by MEDSIR reflect its pivotal approach and commitment to innovation in personalized treatments, highlighting advances in prostate (ZZFIRST study), breast (ABIGAIL), thymic (PECATI) and lung (I3Lung.) cancers. Among these, the I3Lung study, funded by the European Union, integrates artificial intelligence models to optimize individualized treatments, reaffirming MEDSIR’s commitment to cutting-edge research. These studies underscore the strong commitment to significantly expand therapeutic options for patients facing complex and difficult-to-treat cancers.

Among the most relevant studies is ABIGAIL, in patients with HR+/HER2- advanced breast cancer and poor prognosis criteria. Its objective is to provide consistent evidence that the treatment strategy with abemaciclib (a CDK4/6 inhibitor) in combination with endocrine therapy as first-line treatment in advanced breast cancer is not inferior to paclitaxel (the standard chemotherapy commonly used in this type of patient) in terms of overall response rate and safety during the first 12 weeks. The aim of this study is to provide hope to patients by offering a chemotherapy-free treatment option. The overall response rate at 12 weeks was markedly better in the group treated with the combination of abemaciclib and endocrine therapy (59%) compared to the group receiving chemotherapy (40%).

"The data from the ABIGAIL study are a crucial step forward for patients with HR+/HER2- advanced breast cancer. The possibility of offering a chemotherapy-free alternative not only improves quality of life, but also offers new perspectives for these patients with poor prognostic criteria. This study reinforces our commitment to finding more effective and less aggressive therapeutic solutions for those who need it most," adds Dr. Juan de la Haba, principal investigator of the study and oncologist at the Reina Sofia University Hospital in Córdoba (Spain).

Another highlight of the congress was the oral presentation of the PECATI study, aimed at patients with thymic tumors, a rare disease that includes thymomas and thymic carcinomas. To date, there have been no standard treatments for metastatic thymic carcinomas beyond chemotherapy, and therapeutic advances in this field have been scarce due to the low prevalence of the disease. The study, an international initiative conducted in 10 hospitals in Spain, Italy and France, evaluated the efficacy of combining two drugs, lenvatinib and pembrolizumab (immunotherapy treatment), in patients with advanced and previously treated thymic tumors. The results were positive, as 88% of the patients had no disease progression during the first 5 months of treatment, and in more than half of the patients (62%) the disease had not progressed at 12 months after the start of treatment.

These findings highlight the potential efficacy of this combination therapy and could be considered a future gold standard treatment for this pathology. "These results are truly promising. Thanks to research, we are opening up new therapeutic possibilities that make a difference in patients’ lives. While research is essential to improve treatments in any type of cancer, it becomes even more relevant in rare tumors such as thymomas, where treatment options are more limited," says Dr. Jordi Remon, principal investigator of the study and medical oncologist at the Institut Gustave Roussy in Paris, France.

These positive results not only reflect a significant advance in the treatment of patients with limited therapeutic options, but also consolidate the importance of innovation and the integration of new treatments in the optimization of therapeutic regimens. MEDSIR is thus positioned at the forefront of oncology research, pushing the frontier of scientific knowledge towards new therapeutic possibilities.

Advancing research in the area of brain metastases

In addition, the company led a symposium on brain metastasis (September 14th), which addressed the essential role of Investigator-Initiated Trials (IITs) and pharmaceutical industry-sponsored trials in revolutionizing our understanding and treatment strategies for one of the biggest challenges, brain metastasis. This remains a critical unmet need, particularly in solid tumors such as lung, breast, and skin cancers.

As a tough challenge in oncology, brain metastasis requires innovative solutions and collaborative efforts. The event, named MEDTalks, featured chairs like Prof. Antonio Llombart, MEDSIR Senior Scientific Lead, and Prof. Mathias Preusser, Head of the Clinical Division of Oncology at the Medical University of Vienna.

During a 360° overview of the biology, pathology, and development of brain metastases, along with recent advancements in systemic management, speakers focused on groundbreaking new drugs, such as Antibody-Drug Conjugates (ADCs) and radio-ligands, delving into the emerging field and potential of theranostics in oncology.

On September 16, 2024 Antennova, a clinical-stage biotech company focused on oncology reported that it presented the latest data of CD73 small molecule inhibitor ATN-037 in a Mini Oral presentation at the 2024 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (ESMO Congress 2024) (Press release, Antennova, SEP 16, 2024, View Source;including-a-dcr-of-89-5-in-a-mini-oral-at-esmo-congress-2024–302247371.html [SID1234646676]).

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Details of the Presentation:
ATN-037 (also known as ATG-037, CD73 Oral Small Molecule Inhibitor)
Title: A First-In-Human Phase I/Ib study of ATG-037 Monotherapy and Combination Therapy with Pembrolizumab in Patients with Advanced Solid Tumours – STAMINA-01
Abstract: 6067
Presentation Number: 997MO

ATN-037 is a highly potent oral small molecule inhibitor of CD73. The STAMINA-01 Phase I/II study was designed to evaluate the safety, pharmacokinetics and optimal dose of ATN-037 as a monotherapy or in combination with Merck’s (known as MSD outside of the United States and Canada) anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with refractory/relapsed solid tumors. Antennova has initiated the dose optimization and dose expansion portion of the Phase II STAMINA trial of ATN-037 in Australia and plans to initiate the study in China at the end of October 2024.

As of July 26, 2024, a total of 43 patients were enrolled and treated with ATN-037 monotherapy. 26 of these patients with acquired resistance to CPIs also received ATN-037 in combination with pembrolizumab. Since the beginning of the treatment (C1D1), 42 patients have received at least one tumor evaluation (1 patient was unevaluable).

Efficacy data show that among the 42 evaluable patients who were on the monotherapy, 23 have achieved stable disease (SD).

The 26 evaluable patients who received ATN-037 in combination with pembrolizumab include 9 patients with NSCLC and 10 patients with melanoma. 4 of these patients (2 with NSCLC and 2 with melanoma) have achieved confirmed partial response (PR). In the 19 patients with NSCLC or melanoma, the ORR was 21.1% (4/19) and the DCR was 89.5% (17/19).

During the study, 43 (100%) patients experienced treatment-emergent adverse events (TEAEs); 62.3% were treatment-related). Among them, 16 patients experienced treatment-emergent serious adverse events (TE-SAEs), and 2 of them were treatment related; 18 patients experienced Grade 3 or higher TEAEs, and 4 of them were treatment-related. At 400 mg twice-daily (BID), the study observed one dose-limiting toxicity (DLT) of Grade 3 rash. No Grade 5 treatment-related adverse events (TRAEs) were reported.
Preliminary data observed from Phase I dose escalation of STAMINA study has shown encouraging PR in patients treated with ATN-037 in combination with pembrolizumab with excellent safety profile. The combination of ATN-037 with Pembrolizumab may provide a new therapeutic option for CPI resistant NSCLC and melanoma patients.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On September 16, 2024 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported updated data, including median progression-free survival (mPFS) and overall survival (OS) findings, from the Phase 2 trial of zanidatamab, an investigational dual HER2-targeted bispecific antibody, in combination with chemotherapy as first-line treatment for patients with HER2-expressing advanced or metastatic gastroesophageal adenocarcinoma (mGEA) (Press release, Jazz Pharmaceuticals, SEP 16, 2024, View Source [SID1234646675]).

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Data from 41 patients with HER2-positive mGEA who were treated with zanidatamab in combination with physician’s choice of chemotherapy treatment demonstrated a mPFS of 15.2 [95% CI: 9.5, 33.4] months. After a median duration of follow-up of 41.5 (range, 23.0-52.7) months, the median OS was not mature, a Kaplan-Meier–estimated 24-month OS was 65% [95% CI: 48.0, 78.0] and the 30-month overall survival was 59% [95% CI: 41.0, 73.0].

"Gastroesophageal adenocarcinoma (GEA) represents one of the most common tumor types worldwide; however, developing effective treatment options for GEA patients has been challenging," said Dr. Elena Elimova, lead trial investigator and a medical oncologist at Princess Margaret Cancer Centre, Toronto, Canada. "Despite recent advancements for patients, the sustained clinical antitumor activity seen in this trial demonstrates the potential for zanidatamab to address a significant unmet patient need in HER2-positive GEA."

"The updated results from this Phase 2 trial reaffirm zanidatamab’s potential as a foundational treatment for patients with HER2-positive mGEA and showcase the promise of this HER2-targeted bispecific antibody to treat HER2-expressing cancers," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "We look forward to continuing to advance our broader clinical development program for zanidatamab in GEA, including the Phase 3 first-line clinical trial HERIZON-GEA-01 that is expected to read out in the second quarter of 2025, and other HER2-expressing solid tumors, with the goal of supporting more patients with HER2-positive cancers."

Phase 2 mGEA Trial Results
The data include efficacy and tolerability findings from an ongoing, open-label Phase 2 study (NCT03929666) evaluating zanidatamab in combination with chemotherapy as first-line treatment for patients with HER2-expressing mGEA, which comprises gastric, esophageal and gastroesophageal junction (GEJ) adenocarcinomas. Patients had not received prior HER2-targeted agents nor systemic treatment for mGEA. A total of 46 patients with HER2-expressing mGEA (41 patients with HER2-positive mGEA) were enrolled from 15 sites across the United States, Canada and South Korea, and patients were administered zanidatamab with physician’s choice of chemotherapy treatment. Currently, chemotherapy-based regimens are the standard first-line combination therapy for 1L mGEA.

The longer-term data (median duration of follow-up of 41.5 [range, 23.0-52.7] months) demonstrates the promising antitumor activity of zanidamatab combined with chemotherapy as a first-line therapy for HER2-positive mGEA.

Treatment with zanidatamab resulted in a cORR of 84% [95% CI: 68.0, 94.0], an increase of 5% from the cORR previously reported, and one additional patient achieved a complete response for a total of four patients achieving complete response among 37-response evaluable patients.
The median duration of response was 18.7 months [95% CI: 8.3-NE] with 10 patients having an ongoing response at the time of data cutoff.
The mPFS was 15.2 [95% CI: 9.5, 33.4] months.
The Kaplan-Meier–estimated 24-month OS was 65% [95% CI: 48.0, 78.0] with a 30-month overall survival of 59% [95% CI: 41.0, 73.0].
With additional follow-up, the safety and tolerability profile of zanidatamab plus chemotherapy remained manageable with no new safety signals identified. Diarrhea was the most common Grade 3-4 treatment-related adverse events (TRAEs) (35%); the incidence of Grade 3-4 diarrhea was <15% for patients treated after the implementation of mandated antidiarrheal prophylaxis. Treatment discontinuation due to TRAEs were infrequent, and there were no treatment-related deaths.

These data were presented in a poster session entitled Zanidatamab + Chemotherapy for First-Line Treatment for HER2+ Advanced or Metastatic Gastroesophageal Adenocarcinoma (mGEA) during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting taking place in Barcelona, Spain. The presentation is available to conference registrants on the ESMO (Free ESMO Whitepaper) conference website (Presentation Number 1423P).

Jazz continues to enroll patients in the Phase 3 randomized clinical trial, HERIZON-GEA-01 (NCT05152147), evaluating zanidatamab in combination with chemotherapy plus or minus tislelizumab as a first-line treatment for HER2-expressing mGEA. This is an events-based trial; top-line data from this trial is expected to read out in the second quarter of 2025.

Phase 2 Colorectal Cancer (CRC) Trial Results Presented as Mini-Oral at ESMO (Free ESMO Whitepaper) 2024
In addition to the mGEA trial presentation, a mini-oral was also presented at ESMO (Free ESMO Whitepaper) 2024 from another arm of the same Phase 2, open-label trial (NCT03929666) that includes a cohort of patients with metastatic CRC treated with first-line zanidatamab plus chemotherapy ± bevacizumab (bev). In 11 response-evaluable patients, there were 10 confirmed partial responses and 1 patient with stable disease as a best response. The cORR was 91% (95% CI: 58.7, 99.8) and median duration of response was not reached (2.9+,16.7+ months). All patients experienced TRAEs – Grade 3-4 TRAEs occurred in five (38%) patients, three (23%) of whom experienced diarrhea. No patients discontinued zanidatamab due to a TRAE and there were no treatment-related deaths. Zanidatamab plus chemotherapy ± bev demonstrated encouraging antitumor activity with a generally manageable safety profile as first-line treatment for patients with HER2-positive mCRC.

About Zanidatamab
Zanidatamab is an investigational dual HER2-targeted bispecific antibody that simultaneously binds to two distinct sites on HER2, known as biparatopic binding. This unique design and enhanced binding results in multiple mechanisms of action, including HER2 and HER3 signal blockade, removal of HER2 protein from the cell surface and enhanced immune effector functions, such as complement-dependent cytotoxicity (CDC), which leads to encouraging antitumor activity. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.

The U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review of the Biologics License Application (BLA) for zanidatamab with a Prescription Drug User Fee Act (PDUFA) action date of November 29, 2024. Zanidatamab was also granted Breakthrough Therapy designation in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC) and given two Fast Track designations: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.

About Gastroesophageal Adenocarcinoma
Gastroesophageal adenocarcinoma (GEA) is the fifth most common cancer worldwide, and approximately 20% of patients have HER2–positive disease.1,2,3 HER2–positive GEA has high morbidity and mortality, and patients are urgently in need of new treatment options.

On September 16, 2024 GV20 Therapeutics, a clinical-stage AI-based next generation biotherapeutics company, reported presentation of clinical results from its Phase 1/2 study of GV20-0251 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 in Barcelona, Spain (Press release, GV20 Therapeutics, SEP 16, 2024, View Source [SID1234646674]).

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Dr. Kristopher Wentzel from The Angeles Clinic and Research Institute gave an oral presentation on the clinical data from the monotherapy dose escalation portion of the ongoing study of GV20-0251, a first-in-class antibody targeting the novel immune checkpoint IGSF8, in patients with advanced solid tumors (NCT05669430).

Key highlights from the presentation include:

Patient Population: The study enrolled 38 heavily pre-treated patients across six dose levels and two dosing schedules. The median age was 62 years, with a median of 4 prior lines of treatment.

Safety: GV20-0251 was well-tolerated across all dose levels (0.5 to 20 mg/kg) with no dose-limiting toxicities observed. Most of treatment-related adverse events were grade 1/2, with only one case of grade 3 pneumonitis reported.

Efficacy: Two confirmed partial responses were observed in 12 efficacy-evaluable metastatic cutaneous melanoma patients. Additionally, 14 of 29 efficacy-evaluable patients showed stable disease, including 4 with tumor shrinkage.

Pharmacokinetics: Dose-proportional pharmacokinetics with half-life around 25.6 days and full target occupancy on circulating T cells were observed at doses ≥ 3 mg/kg.
Click here to access the ESMO (Free ESMO Whitepaper) presentation.

"We are excited by these encouraging results for GV20-0251, which represent a significant milestone as the first clinical data for an AI-designed antibody against an AI-predicted target," said Dr. Shirley Liu, Co-founder and Chief Executive Officer of GV20 Therapeutics. "The favorable safety profile and preliminary efficacy signals, particularly in melanoma patients, support the potential of IGSF8 as a novel immune checkpoint target."

GV20-0251 is designed to enhance NK cell killing of malignant cells, upregulate dendritic cell antigen presentation, and increase T cell signaling. This mechanism of action may be particularly relevant for patients with antigen presentation-deficient tumors, which are often resistant to current immune checkpoint inhibitors.

The company is currently recruiting anti-PD1-relapsed and refractory cancer patients to be treated by GV20-0251 in combination with pembrolizumab to further evaluate the drug safety, pharmacokinetics, pharmacodynamics, and efficacy.