On November 29, 2023 Photocure ASA (OSE: PHO), the Bladder Cancer Company, reported that its partner Asieris Pharmaceuticals (SSE: 688176) communicated that the National Medical Products Administration (NMPA) accepted the new drug application (NDA) for Hexvix (APL-1706) in China (Press release, PhotoCure, NOV 29, 2023, View Source [SID1234638057]). Hexvix, a pharmaceutical product used in the detection of bladder cancer, was licensed to Asieris by Photocure in January 2021, for the registration and commercialization of Hexvix in mainland China and Taiwan.

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Results of the Hexvix (APL-1706) Phase III clinical trial in China were presented at the 43rd Congress of the Société Internationale d’Urologie (SIU) last month, as a late-breaking abstract. The study confirmed that, in a Chinese patient population, Hexvix blue light cystoscopy (BLC) outperformed white light cystoscopy (WLC) in the detection of bladder cancer, particularly in cases of carcinoma in situ (CIS), and exhibited good tolerability.

The highly statistically significant results corroborate the findings of Photocure’s own randomized controlled trials (RCTs) that demonstrated the clinical benefits of Hexvix BLC over WLC, specifically superior tumor detection and a favorable tolerability profile with no serious adverse events. Moreover, Asieris’ Phase III Hexvix trial is the first RCT that was conducted with high definition 4K blue light capital equipment.

Hexvix is currently the only approved optical imaging agent for diagnosing and surgical management of patients with bladder cancer worldwide. The combined use of Hexvix (APL-1706) and BLC for the management of non-muscle invasive bladder cancer (NMIBC) has been included in the global expert consensus guidelines and Chinese Urological Association Guideline. The drug has not yet been approved for market launch in China.

"We are glad to see our partners at Asieris driving the submission process with conviction and speed. The acceptance of the Hexvix submission by NMPA is the positive outcome of months of collaboration between the Asieris and Photocure teams," said Dan Schneider, President and CEO of Photocure. "We believe that BLC can make a difference which evident in the robust clinical data from many years of experience and the recent Chinese RCT data presented at SIU earlier this year. Both companies remain committed to bringing Blue Light Cystoscopy with Hexvix to more patients with bladder cancer and elevate the standard of care."

Asieris Pharmaceuticals is a global biopharma company specializing in discovering, developing and commercializing innovative drugs for the treatment of genitourinary tumors and other related diseases.

Read Asieris’ full media release here: View Source

On November 29, 2023 OncoResponse, a clinical-stage biotech company advancing immunotherapies derived from the immune systems of Elite Cancer Responders, reported the dosing of the first participant in the Phase 1/2 trial of OR502, a novel, humanized anti-leukocyte immunoglobulin like receptor B2 (LILRB2) antibody that rescues innate and adaptive immune responses from LILRB2 mediated immune suppression (Press release, OncoResponse, NOV 29, 2023, View Source [SID1234638056]). This Phase 1/2 study is designed to determine the safety, tolerability, and preliminary anti-tumor activity of OR502 administered as a monotherapy and in combination with anti-PD-1 in subjects with advanced solid tumors.

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"Initiating this study in cancer patients reflects our continued commitment to advancing programs that have the greatest potential to improve outcomes for patients undergoing cancer treatment," said Clifford Stocks, Chief Executive Officer of OncoResponse.

"OR502 binds to LILRB2 in a unique way to reverse immunosuppression in cancer and offers a potential treatment option to patients who have otherwise struggled with CPI therapy effectiveness," said Kamal Puri, PhD, Chief Scientific Officer of OncoResponse. "OncoResponse has spent years devising strategies to block or reprogram tumor associated macrophages to drive anti-tumor activity. We are excited by the vast promise of OR502 in the LILRB2 target space with preclinical data showing superiority to other clinically validated anti-LILRB2 antibodies."

About the Phase 1 Trial

This Phase 1/2 study is an open-label, multicenter, first-in-human dose-escalation and expansion study designed to determine the safety, tolerability, and preliminary anti-tumor activity of OR502, a fully human IgG1 antibody that binds specifically to LILRB2. OR502 will be administered as a monotherapy and in combination with anti-PD-1, cemiplimab, in subjects with advanced solid tumors. The study consists of two parts. Part A is a dose-escalation phase to determine the maximum-tolerated dose (MTD) or optimal dose of OR502 for further evaluation as monotherapy and in combination. Part B is an expansion phase in subjects with advanced solid tumors treated with OR502 at two separate doses, to help determine the recommended Phase 2 dose (RP2D) for further development and determine preliminary anti-tumor activity. The role of potential biomarkers will be evaluated throughout the study, and more intensively in a separate biology cohort. Additional details are available on ClinicalTrials.gov, identifier: NCT06090266.

About OR502

LILRB2 is an immunoinhibitory receptor expressed on tumor-associated macrophages (TAMs) found in the tumor microenvironment (TME). TAMs inhibit the activity of checkpoint inhibitor (CPI) therapy and prevent T cells from killing tumors. Blocking the inhibitory activity of TAMs and promoting the activity of tumor-killing T cells reverses inhibition of CPI therapy, potentially leading to more and deeper responses to CPIs in patients. This is the mechanism of OR502, which modulates LILRB2 by blocking its engagement of HLA-G on tumor cells and prevents the suppression of the myeloid cells. Elevated expression of LILRB2 correlates with reduced patient survival in various tumor types. Our humanized monoclonal antibody, OR502, targets LILRB2 and blocks the inhibitory activity of TAMs and promotes the activity of tumor-killing T cells, reversing inhibition of CPI therapy.

On November 29, 2023 AbbVie (NYSE: ABBV) reported topline results from the single-arm Phase 2 LUMINOSITY trial evaluating telisotuzumab-vedotin (Teliso-V) in patients with c-Met protein overexpression, epidermal growth factor receptor (EGFR) wild type, advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC) (Press release, AbbVie, NOV 29, 2023, View Source [SID1234638055]). The results demonstrated a compelling overall response rate per independent central review (ICR) of 35 percent and 23 percent across c-Met High and c-Met Intermediate patients respectively.

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In addition, other endpoints demonstrated meaningful clinical outcomes including median duration of response per ICR of 9 months and 7.2 months and a median overall survival of 14.6 months and 14.2 months across c-Met High and c-Met Intermediate patients respectively.

The safety profile of Teliso-V was consistent with previous findings and no new safety concerns were identified. Adverse events with Teliso-V monotherapy were generally well managed and tolerated. Full data from the LUMINOSITY study will be presented at a future medical meeting and we will discuss with global health authorities the potential to support an accelerated approval.

Approximately 85% of lung cancers are classified as NSCLC1 and despite advances in treatment, lung cancer remains the leading cause of cancer-related deaths in both men and women throughout the world.2 C-Met protein overexpression is found in approximately 25% of advanced EGFR wild type NSCLC patients3 and is associated with a poor prognosis for these patients.4,5,6 Teliso-V, an investigational ADC, is being studied in this patient population who have very limited treatment options and where there are currently no approved therapies.

"The results of the Phase 2 LUMINOSITY trial are encouraging for those patients with non-small cell lung cancer with c-Met overexpression as there is a critical need for better care and additional therapy options for them," said Ross Camidge, MD, PhD, University of Colorado Cancer Center, United States, and Principal Investigator for the trial. "Today’s announcement also provides confidence as we continue to enroll patients into the Phase 3 TeliMET NSCLC-01 trial and expand our understanding of Teliso-V’s potential."

"Results from the Phase 2 LUMINOSITY trial mark an important step forward for AbbVie’s mission to advance new oncology treatments across our ADC program targeting solid tumor types with critical patient needs," said Roopal Thakkar, M.D., senior vice president, development and regulatory affairs and chief medical officer, AbbVie.

Teliso-V is being evaluated as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild type nonsquamous NSCLC in the randomized Phase 3 study TeliMET NSCLC-01, which is currently enrolling.

Teliso-V has also been granted several designations around the world including Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) and Taiwanese health authorities, SAKIGAKE designation in Japan by the Ministry of Health, Labour and Welfare (MHLW), as well as being awarded an Innovation Passport by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).

About Telisotuzumab-Vedotin (Teliso-V)
Teliso-V is an investigational first-in-class, c-Met protein directed antibody-drug conjugate (ADC) targeting patients with c-Met overexpressing tumors. C-Met is a receptor tyrosine kinase that is overexpressed in many solid tumors including NSCLC. Teliso-V is being evaluated as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild type non squamous NSCLC in the randomized Phase 3 study TeliMET NSCLC-01, which is currently enrolling. In addition, it is being evaluated in combination with osimertinib in the ongoing Phase 1 study M14-237, and as a monotherapy in the Phase 2 LUMINOSITY study. Further information on clinical trials for Teliso-V is available at View Source Currently there are no approved cancer therapies specifically for patients with c-Met overexpressing NSCLC. Teliso-V is not approved by any regulatory authority and its safety and efficacy have not been established.

About the LUMINOSITY trial
The LUMINOSITY trial (M14-239), is an ongoing Phase 2 study designed to identify the target NSCLC populations that overexpress c-Met best suited for Teliso-V monotherapy in the second line or third line setting, and then to expand the groups to further evaluate efficacy in the selected populations. The endpoints include overall response rate (ORR), duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS) per independent central review (ICR) as well as overall survival (OS).

On November 29, 2023 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported that the completed Phase II OPALESCENCE investigator-initiated trial (IIT) of its carbonic anhydrase IX (CAIX)-targeting positron emission tomography (PET) imaging candidate, TLX250-CDx (89Zr-DFO-girentuximab), in patients with triple-negative breast cancer (TNBC), will be presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) taking place from December 5-9, 2023 (Press release, Telix Pharmaceuticals, NOV 29, 2023, View Source [SID1234638054]).

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Dr. Caroline Rousseau, Principal Investigator for the OPALESCENCE study (ClinicalTrials.gov ID NCT04758780) at the Institut de Cancérologie de l’Ouest (ICO) in St Herblain (France), will deliver top-line results as a poster presentation at 5pm CT on Wednesday December 6.

The primary objective of the OPALESCENCE study was to evaluate how CAIX-targeted imaging with PET can be utilised for the diagnosis and staging of TNBC and to develop a deeper understanding of CAIX as a potential therapeutic target in this patient population with a significant unmet medical need.

SABCS is the largest and most prestigious scientific gathering on breast cancer research worldwide. Visit View Source for more information on the congress.

On November 29, 2023 Adaptimmune Therapeutics plc (NASDAQ: ADAP), a leader in cell therapy to treat cancer, reported the transfer of the IND for letetresgene autoluecel (lete-cel) from GSK to Adaptimmune for the pivotal IGNYTE-ESO (NCT03967223) clinical trial (Press release, Adaptimmune, NOV 29, 2023, View Source [SID1234638053]).

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Adrian Rawcliffe, Adaptimmune’s Chief Executive Officer: "The compelling clinical data from the pivotal IGNYTE-ESO trial frames lete-cel as the ideal synergistic product to afami-cel and could enable our sarcoma franchise to more than double the addressable patient population. Further, we can deliver lete-cel to market efficiently using the same commercial footprint we intend to use for afami-cel."

Adaptimmune recently reported data from a protocol-defined interim analysis of the pivotal IGNYTE-ESO trial. In this analysis, 40% (18/45) of people with synovial sarcoma or myxoid/ round cell liposarcoma (MRCLS) had confirmed clinical responses with lete-cel by independent review. The primary efficacy endpoint requires 16/60 patients have responses. As a result, the Company is evaluating the integration of lete-cel into its sarcoma franchise and is looking forward to sharing its development plans for lete-cel in the new year.

Lete-cel, an engineered TCR T-cell therapy targeting the solid tumor antigen NY-ESO-1, was originally developed by Adaptimmune, and further developed under a collaboration and license agreement with GSK plc. Lete-cel is being investigated for the treatment of synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) in the pivotal IGNYTE-ESO (NCT03967223) trial in patients who received prior anthracycline treatment. In 2023, Adaptimmune and GSK agreed terms regarding the return of the NY-ESO program back to Adaptimmune. Per the terms of the Agreement, Adaptimmune has received an upfront amount and will receive milestone-based payments totaling £30 million in relation to the transfer of the clinical trials for the NY-ESO targeted programs.

About synovial sarcoma

There are approximately 50 types of soft tissue sarcomas which are categorized by tumors that appear in fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues.1 Synovial sarcoma accounts for approximately 5% to 10% of all soft tissue sarcomas (there are approximately 13,400 new soft tissue cases in the U.S. each year).2 One third of patients with synovial sarcoma will be diagnosed under the age of 30.2 The five-year survival rate for people with metastatic disease is just 20% and most people undergoing standard of care treatment for advanced disease experience recurrence and go through multiple lines of therapy, often exhausting all options.3

1. View Source accessed Oct. 24, 2023
2. Synovial Sarcoma – NCI (cancer.gov) accessed Oct. 24, 2023
3. Aytekin MN, et al. J Orthop Surg (Hong Kong). 2020;28(2)

About Myxoid/round cell liposarcoma (MRCLS)

Myxoid/round cell liposarcoma (MRCLS) is a type of soft tissue sarcoma that is predominantly found in the limbs. MRCLS accounts for approximately 5% to 10% of all soft tissue sarcomas.1 One-third of MRCLS cases will become metastatic with tumors spreading to unusual bone and soft tissue locations. MRCLS commonly presents at an age ranging from 35-55 years and has a poor prognosis because it recurs locally and tends to metastasize quickly and widely. The 5-year survival rate for metastatic MRCLS is only 5%.2

1. View Source accessed Oct. 24, 2023
2. https: www.orpha.net accessed Oct. 24, 2023

Overview of IGNYTE-ESO trial design

IGNYTE-ESO is a Phase 2, open-label trial for people with advanced synovial sarcoma or MRCLS to evaluate the efficacy, safety, and tolerability of lete-cel. Lete-cel’s engineered TCR T-cells target NY-ESO-1+ tumors. NY-ESO-1 is highly expressed in synovial sarcoma and MRCLS in the context of HLA-A*02.

Key eligibility criteria include ECOG performance status of 0 or 1; HLA*02 positive with confirmed NY-ESO expression in ≥ 30% of tumor cells ≥ 2+ by immunohistochemistry; aged ≥ 10 years; and patients must have measurable disease according to RECIST v1.1 at the time of treatment. The IGNYTE-ESO master protocol include two substudies – Substudy 1 was designed to investigate lete-cel in previously untreated advanced (metastatic or unresectable) synovial sarcoma or MRCLS; and Substudy 2 was designed to investigate lete-cel in advanced (metastatic or unresectable) synovial sarcoma or MRCLS post-anthracycline chemotherapy. Eligible patients received lete-cel doses between 1-15 × 10^9 transduced T-cells after receiving lymphodepleting chemotherapy.

Approximately 10 people were planned to be treated in Substudy 1, 5 patients were treated and enrollment was stopped. Approximately 60 people were planned to be treated in Substudy 2 and enrollment is complete.