On June 1, 2023 Bold Therapeutics, a clinical-stage biopharmaceutical company developing first-in-class oncology therapeutics, reported that it will be presenting positive interim results in advanced gastric and biliary tract cancer at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 2-6, 2023 in Chicago, Illinois (Press release, Bold Therapeutics, JUN 1, 2023, View Source [SID1234632367]).

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These results will be presented in the Gastrointestinal (Gastroesophageal, Pancreatic and Hepatobiliary) Cancer session on June 5, 2023 from 8:00AM – 12:00PM CT as Poster 4098: "BOLD-100-001 (TRIO039): A Phase 1b/2a Study of BOLD-100 in Combination with FOLFOX Chemotherapy in Patients with Pre-Treated Advanced Gastric and Biliary Tract Cancer: Efficacy and Safety Analysis." This poster includes progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) data in gastric and biliary tract cancer and expands on data in metastatic colorectal cancer presented earlier this year at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2023 conference. With compelling interim Phase 2 data in three different difficult-to-treat oncology indications (colorectal, gastric, and biliary tract), BOLD-100’s disruptive therapeutic potential is becoming increasingly evident.

BOLD-100 is currently being studied in a global Phase 1b/2 trial for the treatment of advanced gastrointestinal cancers, with 110 patients successfully treated to date. Phase 1b trial results, presented at ASCO (Free ASCO Whitepaper) 2022, demonstrated that BOLD-100 in combination with FOLFOX was generally safe and well-tolerated. Interim Phase 2 data in metastatic colorectal cancer presented at AACR (Free AACR Whitepaper) 2023 indicated that patients treated with BOLD-100 and FOLFOX showed a median PFS of 4.7 months, OS of 9.8 months, ORR of 13%, and DCR of 87%, substantially higher than standard-of-care data (Bayer’s Stivarga and Taiho’s Lonsurf) for a similar patient population which showed a median PFS of up to 2.0 months, OS of up to 7.1 months, ORR of up to 1.6%, and DCR of up to 44%. In addition, BOLD-100 in combination with FOLFOX proved to be exceptionally well-tolerated, with no new safety signals, and with patients remaining on therapy for up to 15 treatment cycles. Data from the full Phase 2 trial, which will include an additional 20 patients with advanced colorectal cancer, should be available in late 2023.

Bold Therapeutics’ BOLD-100 is a first-in-class ruthenium-based small molecule therapeutic that (1) alters the unfolded protein response (UPR) through selective GRP78 inhibition; and (2) induces reactive oxygen species (ROS) which causes DNA damage and cell cycle arrest. Collectively, these effects result in cell death in both sensitive and resistant cancers, giving BOLD-100 the potential to significantly improve outcomes in a wide range of both solid and liquid tumors in combination with other anticancer therapies ranging from traditional chemotherapies to targeted therapies and immuno-oncology agents.

BOLD-100 was previously granted orphan drug designations (ODDs) in gastric and pancreatic cancer and expects additional ODDs and/or breakthrough therapy designations (BTDs) expected in 2023 and 2024. Bold Therapeutics is preparing to initiate a pivotal Phase 3 trial for BOLD-100 in the treatment of advanced colorectal cancer in 2024 and is currently evaluating potentially synergistic development and commercialization partnerships to support these efforts. Concurrently, Bold Therapeutics is exploring additional development indications for BOLD-100 while also advancing its pipeline of other novel metallotherapeutics.

On June 1, 2023 GenEros Biopharma Ltd. ("GenEros" or "the Company"), a biopharmaceutical company dedicated to discovering, developing, and commercializing novel medicines for diseases with unmet medical needs, reported that it will unveil the preliminary data from the phase I clinical trial of GEC255, a unique KRAS G12C inhibitor, at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, GenEros Biopharma, JUN 1, 2023, View Source [SID1234632366]).

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As of the data cutoff date of February 3, 2023, preliminary data from the study (NCT05768321) sponsored by GenEros Biopharma demonstrated encouraging results. Sixteen NSCLC patients with the KRAS G12C mutation were enrolled in the Phase I dose escalation, followed by dose expansion in selected doses. All patients were at clinical stage IIIC-IV and had undergone a median of 1 (range 0-6) prior systemic treatments, including platinum-based chemotherapy (75%) and immune checkpoint inhibitors (44%).

Tumor response was evaluated in 13 subjects at least once. Among them, 10 subjects (76.9%) achieved objective responses (complete or partial response), while 12 subjects (92.3%) demonstrated disease control (objective response or stable disease). In the 600mg dose group, the objective response rate (ORR) was 83.3%, and the disease control rate (DCR) was 100% (n=6). Notably, significant efficacy was observed at low doses of 200mg and 400mg QD, with some patients achieving partial response for over a year and continuing to benefit.

Fifteen patients experienced treatment-related adverse events, primarily Grade 1 or Grade 2. The most common adverse events (AEs) included diarrhea, ALT increase, rashes, and anemia. No dose-limiting toxicity was observed, and the maximum tolerated dose (MTD) has not been reached.

The KRAS G12C mutation occurs in approximately 12-14% of non-small cell lung cancer (NSCLC) patients. This mutation leads to uncontrolled cell growth and proliferation, contributing to cancer development.

GEC255, a novel and innovative small molecule with high selectivity, excellent target engagement ability, and a favorable pharmacological profile, has demonstrated promising anti-tumor activity in advanced non-small cell lung cancer (NSCLC) patients with the KRAS G12C mutation. It stands as a potential best-in-class KRAS G12C inhibitor.

"The trial results are highly encouraging," stated Dr. You Lu, the lead investigator of the trial. "GEC255 has shown significant anti-tumor activity in advanced NSCLC patients who have not responded to other treatments. These results justify further investigation of GEC255 in larger clinical trials."

2023 ASCO (Free ASCO Whitepaper) Annual Meeting Presentation Details:
Title: Phase I study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of GEC255, a novel KRASG12C inhibitor, in advanced solid tumors
Abstract #: 9112 | Poster Bd #:100
Session: Lung Cancer—Non-Small Cell Metastatic
Date and Time: June 4, 2023, at 8:00 – GMT-5 11:00

On June 1, 2023 TORL BioTherapeutics LLC ("TORL Bio" or "the Company") reported the initial results from an ongoing phase I study of their claudin 6 (CLDN6) targeted antibody drug conjugate (ADC), TORL-1-23, in patients with advanced cancer on the American Society of Oncology (ASCO) (Free ASCO Whitepaper) website : View Source (Press release, TORL Biotherapeutics, JUN 1, 2023, View Source [SID1234632365]). The poster presentation (ASCO Abstract 3082) of the TORL123-001 (TRIO-049) trial will include updated data through the 2.4mg/kg dose level and will be presented by the Global Principal Investigator, Dr. Gottfried Konecny of the University of California Los Angeles (UCLA) Medical Center.

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Twenty-five (25) patients with heavily pretreated (an average of 5 prior lines of therapy) metastatic ovarian (n=19), testicular (n=3), and endometrial (n=3) cancers were enrolled and evaluable for safety and efficacy across 8 dose levels ranging from 0.2 to 2.4 mg/kg IV every 3 weeks. "We are excited to provide the first clinical data with TORL-1-23, a novel claudin 6 targeted ADC" stated Dave Licata, CEO and Co-Founder of TORL Bio. "We are very encouraged by the current TORL-1-23 efficacy and safety data indicating that this drug could represent a new potential treatment for patients with ovarian and other CLDN6+ cancers" said Dennis Slamon, MD, PhD, and Co-Founder of TORL Bio.

Key study findings include:

TORL-1-23 is well tolerated with no dose limiting toxicities from 0.2 to 2.4 mg/kg IV every 21 days
Confirmed responses were observed in 7/25 (28%) patients across all dose levels and all patients treated with TORL-1-23
Confirmed responses were observed in 6/19 (32%) patients with platinum-resistant ovarian cancer across all dose levels, with 3/4 (75%) responses at the 2.4 mg/kg dose level
Pharmacokinetic data indicate sustained exposure of TORL-1-23 over the 21-day dosing period and low levels of free MMAE payload
Expansion cohorts are planned in CLDN6+ ovarian cancer and non-small cell lung cancer (NSCLC), and other CLDN6+ cancers upon determination of the recommended phase 2 dose (RP2D).

Poster Presentation Details:
Title: Initial results of dose finding in a first-in-human phase I study of a novel Claudin 6 (CLDN6) targeted antibody drug conjugate (ADC) TORL-1-23 in patients with advanced solid tumors.
Lead author: Gottfried E. Konecny, M.D, University of California Los Angeles Medical Center, Los Angeles, CA
Abstract #: 3082
Poster Board #: 280
Session Title: Developmental Therapeutics-Molecularly Targeted Agents and Tumor Biology
Session Date and Time: June 3, 2023, 8:00-11:00 a.m. CT
View Source

About TORL-1-23

TORL-1-23 is an anti-CLDN6 humanized monoclonal antibody coupled to MMAE via a cleavable linker. CLDN6 is overexpressed in multiple cancers with limited to no detectable expression in normal tissues, thus an ideal target for an ADC. TORL 1-23 is highly selective; in vitro TORL-1-23 exhibited robust and selective binding to CLDN6-overexpressing cell lines without binding to cell lines over-expressing other claudins, such as CLDN3, CLDN4, and CLDN9. TORL-1-23 is in clinical trials for treatment of CLDN6+ cancers including ovarian cancer and NSCLC.

About TORL123-001 (TRIO-049) Clinical Study

TORL BioTherapeutics is currently enrolling patients in a phase I study, TORL123-001 (TRIO-049), to assess the safety, pharmacokinetics, biomarkers, and antitumor activity of TORL-1-23. Further details including current study sites can be found at View Source

On June 1, 2023 Florida Cancer Specialists & Research Institute, LLC (FCS) physicians are presenting the outcomes of 23 clinical trials, the majority being Phase 1, at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 2 – 6 in Chicago, Illinois (Press release, Florida Cancer Specialists & Research Institute, JUN 1, 2023, View Source;research-institute-cutting-edge-clinical-research-presented-at-2023-asco-annual-meeting-301840543.html [SID1234632364]). With over 120 abstract sub-categories, attendees will learn about the most advanced treatments, research and innovations in oncology care on a global scale.

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Many of the featured studies being presented at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting originated from trials conducted at the three FCS Phase 1 Drug Development Units and from late-phase studies conducted at FCS clinics located throughout Florida.

"The diverse range of clinical research taking place across our FCS network is at the cornerstone of our quest to conquer cancer and contributing to global breakthroughs that are providing new hope to those living with cancer," said FCS Director of Clinical Research Gustavo Fonseca, MD, FACP.

FCS President & Managing Physician Lucio N. Gordan, MD is first author for a published study on ovarian cancer and is co-author of a poster presentation on non-small cell lung cancer.

FCS Director of Drug Development Manish R. Patel, MD is first author of two poster presentations, one on the results of a Phase 1 study on advanced solid tumors and the second, a Phase 1/2 study of relapsed/refractory B or T-cell lymphoma. Dr. Patel is co-author of five additional Phase 1 trials on solid tumors published or shared in poster presentations.

FCS Associate Director of Drug Development Judy Wang, MD will present as first author the results of a Phase 1 dose-escalation study of advanced solid tumors in a poster presentation.

FCS medical oncologist Cesar Augusto Perez, MD is co-author of two poster presentations on early-stage trials of solid tumors and a published study on solid tumors. Additionally, Dr. Perez is serving as Leader of the Head and Neck Educational Committee for the ASCO (Free ASCO Whitepaper) annual meeting and is a member of the Head and Neck Scientific Committee. He will chair a discussion on developments in the treatment of head and neck cancer.

The following FCS physician investigators will present research results during oral presentations:

FCS hematologist and medical oncologist Alexander Philipovskiy, MD, PhD – Phase 1 study of recurrent high-grade glioma and uveal melanoma
FCS hematologist and medical oncologist Vance M. Wright-Browne, MD – Phase 2 study of metastatic breast cancer, co-authored with FCS hematologist and medical oncologist Jennifer L. Cultrera, MD
The following FCS physician investigators will present research results during poster presentations/discussions and publications:

FCS hematologist and medical oncologist Raymond Esper, MD, PhD – non-small cell lung cancer
FCS hematologist and medical oncologist Sunil Gandhi, MD, FACP – non-small cell lung cancer
FCS Scientific Director of Clinical Research Lowell L. Hart, MD, FACP – breast cancer
FCS hematologist and medical oncologist Maen Hussein, MD – solid tumors
FCS hematologist and medical oncologist Shachar Peles, MD – outcome of deep venous thrombosis and pulmonary embolism in COVID-19 cancer patients vs non-cancer patients
Additionally, FCS investigators participated in a published study of clonal hematopoiesis and a Phase 2 study on melanoma that will be presented in a poster presentation.

Manish R. Patel, MD, FCS Director of Drug Development, said, "The early-stage research conducted at FCS is among the initial steps in determining new therapies that are increasingly becoming first-line standard of care for patients worldwide. We are delighted to share the impact of our work in this prestigious setting."

"It is rare for a community oncology practice to offer patients such extensive opportunities to participate in clinical trials," said Lucio N. Gordan, MD, FCS President & Managing Physician. "Patients who entrust their care to FCS are receiving the most advanced therapies available, close to home."

The American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) represents nearly 45,000 oncology professionals who care for people living with all forms of cancer. Through research, education and promotion of high quality and equitable patient care, ASCO (Free ASCO Whitepaper) works to conquer cancer.

On June 1, 2023 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, reported that it has entered into a clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany for the combination therapy of IBI351 (GFH925) with cetuximab (ERBITUX) as a potential frontline treatment for NSCLC patients harboring KRASG12C mutation in a Phase 1b clinical trial in China (Press release, Innovent Biologics, JUN 1, 2023, View Source [SID1234632363]).

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Under the agreement, Innovent will conduct a Phase 1b study to evaluate the anti-tumor activity and safety of the combination therapy of IBI351(GFH925) with cetuximab in Chinese patients with advanced or metastatic NSCLC harboring KRASG12C mutation. Merck KGaA, Darmstadt, Germany will provide clinical drug supplies of cetuximab in this multi-center trial in China. Cetuximab as a monotherapy or as a combination therapy has not been approved in any country for patients with advanced NSCLC.

Currently, Innovent is conducting a single-arm registrational trial of IBI351(GFH925) monotherapy in previously-treated advanced non-small cell lung cancer patients with KRASG12C mutation in China, with expected NDA filing by the end of 2023. A Phase 1b study of IBI351(GFH925) in combination with sintilimab for previously untreated advanced NSCLC patients with KRASG12C mutation is also under exploration. Latest data of a Phase 1 study of IBI351(GFH925) monotherapy in 67 previously-treated NSCLC patients with KRASG12C mutation were presented at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper)(AACR) Annual Meeting [Link].

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to collaborate with Merck KGaA, Darmstadt, Germany to further explore the potential of IBI351 and cetuximab combination therapy in the early line setting for NSCLC patients harboring KRASG12C mutation, and shed light on next-step clinical development. The combination of a KRASG12C inhibitor and an EGFR inhibitor has shown efficacy in heavily pre-treated patients with metastatic colorectal cancer [1],[2],[3]. Preclinical studies of IBI351 and cetuximab combination therapy also demonstrated potential anti-tumour activity in NSCLC. Innovent has observed favorable safety and promising antitumor activity of IBI351 monotherapy in previously-treated advanced NSCLC harboring KRASG12C mutation, and we are actively expanding treatment lines, hoping to provide better treatment options for more cancer patients. "

About IBI351/GFH925 (KRASG12C Inhibitor)

RAS protein family can be divided into KRAS, HRAS and NRAS categories. KRAS mutation are detected in nearly 90% of pancreatic cancer, 30-40% of colon cancer, and 15-20% lung cancer patients. The occurrence of KRAS G12C mutation subset is more frequently observed than those with ALK, ROS1, RET and TRK 1/2/3 mutations combined.

Discovered by GenFleet Therapeutics, GFH925 (Innovent R&D code: IBI351) is a novel, orally active, potent KRASG12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRASG12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of IBI351 towards G12C. Subsequently, IBI351 effectively inhibits the downstream signal pathway to induce tumor cells’ apoptosis and cell cycle arrest.

In September 2021, Innovent and GenFleet Therapeutics entered into an exclusive license agreement for the development and commercialization of IBI351 in China (including mainland China, Hong Kong, Macau and Taiwan) with additional option-in rights for global development and commercialization.

In January 2023, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI351 for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring KRASG12C mutation who have received at least one systemic therapy. In May 2023, the CDE of China’s NMPA granted another BTD for IBI351 for the treatment of previously treated advanced colorectal carcinoma (CRC) patients with KRASG12C mutation.

About Cetuximab (ERBITUX)

Cetixumab (ERBITUX) is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of cetuximab is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth. Based on in vitro evidence, cetuximab also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody-dependent cell-mediated cytotoxicity [ADCC]).

ERBITUX has already obtained market authorization in over 100 countries worldwide for the treatment of RAS wild-type metastatic colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck. Merck licensed the right to market ERBITUX, a registered trademark of ImClone LLC, outside the U.S. and Canada from ImClone LLC, a wholly owned subsidiary of Eli Lilly and Company, in 1998.