On June 3, 2024 Fulgent Pharma, a subsidiary of Fulgent Genetics, Inc. (NASDAQ: FLGT) and a leading nanobiotechnology company specializing in innovative cancer therapeutics, reported that Phase 1 clinical data on its lead therapeutic development candidate, FID-007, to treat Head and Neck cancer, was presented at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 2, 2024 in Chicago, Illinois (Press release, Fulgent Pharma, JUN 3, 2024, View Source [SID1234644064]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Of eleven head and neck squamous cell carcinoma (HNSCC) evaluable patients with weekly dose levels from 15 mg/m2 to 160 mg/m2, five (45%) had a partial response and three (27%) had stable disease by RECIST. Three out of five HNSCC patients with PR had previously been treated with taxane. The duration of follow-up (months), median (range) is 4.0 (1.0 – 15.0). No high-grade neuropathy has been noted to date. FID-007 demonstrates preliminary evidence of anti-tumor activity in heavily pre-treated HNSCC patients across different primary tumor sites, with an overall response rate of 45%. Phase 2 study of FID-007 combination with cetuximab in patients with HNSCC has begun enrollment.

Commenting on the data, Ming Hsieh, Chairman of the Board and Chief Executive Officer, said, "We are very encouraged by the data from these Head and Neck cancer patients, in particular the preliminary evidence of relatively lower toxicity and improved treatment tolerance with FID-007 compared to prior therapies. These data support the Phase 2 clinical study we recently began in head and neck squamous cell carcinoma, and we look forward to bringing FID-007 to more patients as we continue enrollment."

The poster is available on the News & Events section of the company’s Investor Relations website at View Source

About FID-007

FID-007 consists of paclitaxel encapsulated in a polyethyloxazoline (PEOX) polymer excipient designed to enhance PK, biodistribution, and tolerability. In addition to allowing the drug to remain in solution until it can enter a cancer cell, the PEOX nanoparticle is designed to preferentially deliver paclitaxel to the tumor through the leaky hyperpermeable vasculature.

On June 3, 2024 Novocure (NASDAQ: NVCR) reported the presentation of clinical data from the phase 3 METIS trial, which investigated the use of Tumor Treating Fields (TTFields) therapy in the treatment of brain metastases from non-small cell lung cancer (NSCLC) (Press release, NovoCure, JUN 3, 2024, View Source [SID1234644063]). These data will be presented at the ongoing 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The METIS trial enrolled 298 adult patients with 1-10 brain metastases from NSCLC, who were randomized following stereotactic radiosurgery (SRS) to receive either TTFields therapy and best supportive care (BSC) (n=149) or BSC alone (n=149). METIS met its primary endpoint, demonstrating a statistically significant improvement in time to intracranial progression. Patients treated with TTFields therapy and BSC exhibited a median time to intracranial progression of 21.9 months compared to 11.3 months in patients treated with BSC alone (hazard ratio=0.67; P=0.016). Median TTFields therapy duration was 16 weeks and median usage was 67%. Baseline patient demographics and characteristics were well balanced between arms.

Patients treated with TTFields therapy demonstrated improved quality of life deterioration-free survival, with median time to quality of life deterioration-free survival not reached in the TTFields therapy cohort compared to 7.7 months in control arm (P=0.038). A positive trend was observed in patients treated with TTFields therapy in the majority of scales and items assessed by the EORTC QLQ C30 and BN20 patient questionnaire. There was no evidence of worsening cognitive functioning in the TTFields therapy arm compared to the control arm. Consistent with prior clinical trials, TTFields therapy was well-tolerated with no additive systemic toxicity.

Preliminary analyses of key secondary endpoints did not demonstrate statistical significance. Median overall survival for patients randomized to receive TTFields therapy and BSC was 11.3 months compared to 10.6 months in patients treated with BSC alone. Full analysis of secondary endpoints is ongoing.

"One of the key challenges in combatting the spread of brain metastases is maintaining patients’ quality of life and cognitive function," said lead investigator Minesh Mehta, MD, Chief of Radiation Oncology and Deputy Director at Miami Cancer Institute, part of Baptist Health South Florida. "The ability of TTFields therapy to prolong the time to intracranial progression without negatively impacting either quality of life or cognitive function has the potential to change the way brain metastases from non-small cell lung cancer are treated."

"Despite the high incidence level of brain metastases from NSCLC, the treatment options available for patients are very limited," said Nicolas Leupin, MD, Novocure’s Chief Medical Officer. "The observations from the METIS trial are an important first step in potentially adding a new treatment option for these patients and we are eager to pursue the necessary steps to ensure TTFields therapy is available to those in need."

These data will be featured by Dr. Mehta in an oral presentation (abstract #2008) at 10:24 a.m. CDT on Monday, June 3, 2024 during ASCO (Free ASCO Whitepaper)’s Central Nervous System Tumors session. Novocure intends to publish these findings in a peer-reviewed scientific journal and submit these data to regulatory authorities.

About METIS

METIS [NCT02831959] is a phase 3 trial of stereotactic radiosurgery with or without TTFields therapy for patients with 1-10 brain metastases from NSCLC. 298 adult patients were enrolled in the trial and randomized to receive either TTFields therapy with supportive care or supportive care alone following SRS. Supportive care consisted of, but was not limited to, treatment with steroids, anti-epileptic drugs, anticoagulants, pain control or nausea control medications. Patients in both arms of the study were eligible to receive systemic therapy for their NSCLC at the discretion of their treating physician. Patients with known tumor mutations for which targeted agents are available were excluded from the trial.

The primary endpoint of the METIS trial is time to first intracranial progression, as measured from the date of first SRS treatment to intracranial progression or neurological death (per RANO-BM criteria), whichever occurs first. Time to intracranial progression was calculated according to the cumulative incident function. Patient scans were evaluated by a blinded, independent radiologic review committee. Secondary endpoints include, but are not limited to, time to distant progression, time to neurocognitive failure, overall survival, time to second intracranial progression, quality of life and adverse events. Key secondary endpoints (time to neurocognitive failure, overall survival, and radiological response rate) were planned to be used in labeling claims, if successful. Full analysis of secondary endpoints is ongoing. Patients were stratified by the number of brain metastases (1-4 or 5-10 metastases), prior systemic therapy, and tumor histology. Patients were allowed to crossover to the experimental TTFields therapy arm following confirmation of second intracranial progression.

About Tumor Treating Fields Therapy

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. The multiple, distinct mechanisms of TTFields therapy work together to selectively target and kill cancer cells. Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or targeted therapies in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors. To learn more about Tumor Treating Fields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.

On June 3, 2024 Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, reported updated data from the ongoing Phase 1 first-in-human, dose-escalation study of OBX-115, a novel engineered tumor-derived autologous T-cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15), in patients with immune checkpoint inhibitor (ICI)-resistant advanced or metastatic melanoma (Press release, Obsidian Therapeutics, JUN 3, 2024, View Source [SID1234644062]). These data were presented in an oral presentation delivered by Rodabe Amaria, M.D., professor of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center and principal investigator of the study, at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The oral presentation for the single-center study (NCT05470283) included a 3-month incremental data update (relative to published abstract) on safety (N=10) and efficacy (n=9 per-protocol efficacy analysis set) for patients with advanced or metastatic melanoma.

Summary of OBX-115 Safety and Efficacy Data (April 4, 2024 data cutoff):

OBX-115 Exhibits Positively Differentiated Safety Profile Relative to IL2-Dependent Non-Engineered TIL Cell Therapy:

All 10 infused patients were alive at data cutoff (median study follow up of 29.5 weeks).
No patient received care in the intensive care unit.
No dose-limiting toxicities were observed at any dose level.
No Grade 4 or higher non-hematologic treatment-emergent adverse events (TEAEs) were reported; 2 patients experienced limited Grade 3 non-hematologic TEAEs.
No confirmed events of cytokine release syndrome, capillary leak syndrome, or immune effector cell-associated neurotoxicity syndrome were reported.
OBX-115 Sustains Consistent Efficacy Profile, without IL2 Administration, in Patients with Substantially Pre-Treated Resistant/Refractory Disease:

Patients had disease that was predominantly ICI primary-resistant, with a median of 3.5 (range, 1–6) lines of prior systemic therapy, including a median of 2 (1–3) lines of prior ICI therapy.
44% objective response rate (ORR), including 2 complete responses (CRs), using investigator-assessed RECIST 1.1 criteria across all doses (n=9 per-protocol efficacy analysis set).
50% ORR in patients who received OBX-115 dose of >30 × 109 cells (n=6).
100% disease control, defined as CR, PR, or ≥12-week duration of stable disease post OBX-115 infusion.
Progression-free survival (PFS) was 75% at 24 weeks.
Tumor burden reduction in all 9 patients, including several with tyrosine kinase inhibitor (TKI)-refractory disease and / or prior treated brain metastasis.
Disease control and responses observed with both fresh and cryopreserved OBX-115 product.
Additional OBX-115 Data Contributing to an Optimized Cell Therapy Product:

Robust manufacturing process observed for OBX-115, including from tumor tissue obtained using core needle biopsy.
Median manufactured OBX-115 dose (N=10): 100 × 109 cells.
Translational data highlight that the OBX-115 infusion product is optimized for response and persistence: predominantly CD8+ cytotoxic T-cell population, effector memory phenotype, high proportion of CD8+CD39-CD69- (double-negative) "stem-like" progenitor cells and low levels of exhaustion markers.
Dr. Amaria commented, "OBX-115 continues to demonstrate positive safety and efficacy data in additional patients, which is encouraging, given this is a heavily pre-treated patient population with advanced disease. Unfortunately, late-line systemic therapy options offer limited benefit, with ORR of approximately 10% and mPFS of approximately 2–3 months. It is exciting to see a potential new option emerge for these patients with a positively differentiated safety profile and promising early activity achieved without IL2."

"We believe OBX-115 has the potential to advance the TIL cell therapy field in multiple ways, including enabling non-surgical tumor tissue procurement and abrogating the need for IL2. We are also exploring the ability to re-energize engrafted OBX-115 cells with acetazolamide re-dosing," commented Parameswaran Hari, M.D., Chief Development Officer of Obsidian. "We look forward to continuing to build on this momentum and apply key learnings from the first-in-human Phase 1 study to our ongoing Phase 1/2 multicenter study, where we are continuing to explore these attributes and optimize the OBX-115 regimen in melanoma and non-small cell lung cancer."

Obsidian is actively enrolling patients with advanced or metastatic melanoma and non-small cell lung cancer (NSCLC) at multiple sites in its ongoing Phase 1/2 multicenter study. Additional details may be found at clinicaltrials.gov, using identifier: NCT06060613.

About OBX-115

Obsidian’s lead investigational cytoTIL15 program, OBX-115, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, antitumor activity, and clinical safety of TIL cell therapy. OBX-115 is being investigated in two ongoing clinical trials in advanced or metastatic melanoma and NSCLC (NCT05470283 and NCT06060613).

On June 3, 2024 Debiopharm (www.debiopharm.com), a privately-owned, Swiss-based, biopharmaceutical company aiming to establish tomorrow’s standard-of-care to cure cancer and infectious diseases, reported the signing of an exclusive licensing agreement with Genome & Company (View Source), a publicly-traded, South Korea-based, biotechnology company focusing on discovery and development of novel target antibody therapeutics, for the development of antibody drug conjugates (ADCs) with first-in-class potential (Press release, Debiopharm, JUN 3, 2024, View Source [SID1234644061]). The agreement offers Debiopharm exclusive global rights to develop ADCs combining specific Genome and Company antibodies with Debiopharm’s innovative linker technology, Multilink, to create highly innovative therapeutic agents to outsmart hard-to-treat cancers.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

ADCs are cutting-edge oncology therapeutics that combine three components: a monoclonal antibody, a stable linker and one or more potent cytotoxic payload. These targeted compounds identify and dock onto specific antigens on cancer cell surfaces and promote targeted delivery of toxic payloads to antigen-expressing cancer cells. This modality improves therapeutic effectiveness while diminishing systemic toxicity and side effects typically associated with conventional cancer treatments. This distinctive capacity to selectively eliminate cancer cells while preserving healthy tissues has granted visibility to ADCs within the pharmaceutical development community. With the ever-growing interest in ADC development, linker design has increasingly become a critical determining factor, as few linkers provide satisfactory stability required for specific and effective drug release.1

"Building on our fruitful collaboration with Genome & Company, the potential of developing this novel antibody family with our proprietary MultilinkTM cleavable linker technology is an exciting opportunity. We recognized that Genome’s innovative antibodies were the right fit for our development focus due to the novelty of the target and its expression in tumor types with high unmet needs" expressed Frederic Levy, Chief Scientific Officer. "This extended collaboration with Genome & Company’s antibody against a novel target represents our commitment to form strategic partnerships for the development of first-in-class and best-in-class ADCs leveraging our proprietary Multilink technology, offering unique linker characteristics that grant a higher stability and DAR, thereby optimizing treatment specificity and effectiveness."

Debiopharm is focused on further expanding their ADC platform, exploring proprietary novel bispecific ADCs and potential game changing technologies such as novel payloads, dual payloads, and degraders, leveraging their solid drug development experience to accelerate ADC products to patients.

"This agreement represents our first out-license deal in the field of novel target anti-cancer therapy of Genome & Company, and we were able to achieve meaningful results in early preclinical stage based on our excellent research and development capabilities," commented Yoo Seok Hong, CEO of Genome & Company. "We expect to show results from our subsequent pipeline of novel target anti-cancer drugs in the near future, leveraging this license deal."

About Multilink

Multilink is a new cleavable linker platform suited for multidrug attachment and compatible with any conjugation technology to produce ADCs with high DAR (drug-to-antibody ratio). This unique and innovative technology allows the loading of multiple payloads on an antibody for an enhanced therapeutic effect. This highly effective and well-tolerated linker platform is available for use by other specialty biotech or pharmaceutical companies to generate proprietary, clinical-stage ADCs.

On June 3, 2024 ImmuneOncia (CEO Heung Tae Kim) reported the results of its solid tumour Phase 1a clinical trial of IMC-002, an anti-CD47 mAb, presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting held in Chicago, USA on June 1, 2024 (local time) (Press release, ImmuneOncia Therapeutics, JUN 3, 2024, View Source [SID1234644060]). These results include updates on the Phase 1a clinical trial outcomes, along with biomarker findings achieved through collaboration with Lunit (CEO; Brandon Suh), a leading provider of AI-powered solutions for cancer diagnostics and therapeutics.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The study, a dose escalation part of Phase 1, enrolled a total of 12 patients across four dose cohorts starting from May 2022. Each patient received IMC-002 at doses of 5, 10, 20, or 30 mg/kg every two weeks. Treatment outcomes revealed stable disease (SD) in 6 out of 12 evaluable patients, demonstrating a disease control rate (DCR) of 50%. Among these, 5 patients had hepatocellular carcinoma, and 1 had breast cancer. Furthermore, 4 patients maintained stable disease for over 6 months, resulting in a clinical benefit rate (CBR) of 33.3%.

AI-powered biomarker analysis, utilizing Lunit SCOPE IO, revealed that the density of CD47-positive macrophages was numerically higher in the CBR group compared to the non-CBR group (71.0/mm² vs. 44.3/mm²), while the density of CD47-positive tumour cells was similar between the two groups. These findings suggest a correlation between the density of CD47-positive macrophages and treatment response, underscoring the potential significance of targeting CD47 in future therapeutic strategies.

Principal investigator Dr. Ho Yeong Lim of Samsung Medical Center stated, "No dose-limiting toxicities (DLTs) were observed across all cohorts, and common adverse events associated with anti-CD47 therapy such as infusion-related reactions, haemolytic anaemia, thrombocytopenia, and neutropenia were not reported, confirming the high safety profile of IMC-002." He added, "Particularly noteworthy is the absence of long-term toxicity in a patient with hepatocellular carcinoma who has been on single-agent IMC-002 treatment for 15 months, demonstrating a favourable prognosis with stable disease and a 20% reduction in tumour size."

CEO Heung Tae Kim of ImmuneOncia commented, "We previously disclosed the high safety and tolerability of IMC-002, along with the recommended Phase 2 dose (RP2D) of 20 mg/kg every 3 weeks, based on interim results presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) in October 2023." He further stated, "With the Phase 1b trial for IMC-002 initiated last November, we anticipate additional efficacy confirmation for IMC-002 in specific solid tumours with high unmet needs."

About IMC-002

IMC-002 is an immune-checkpoint-inhibitor targeting the CD47 of macrophages, blocking the ‘don’t eat me’ signal of CD47/SIRPα interaction between cancer cells and macrophages to enhance phagocytosis of cancer cells. IMC-002 is a potential first-in-class and second-generation anti-CD47 mAb demonstrating high safety with no commonly associated adverse events (hemagglutination, thrombocytopenia, neutrophilia, etc.) due to minimal binding to normal cells such as red blood cells.