On August 1, 2024 Adaptimmune Therapeutics plc (NASDAQ: ADAP), a company working to redefine the treatment of solid tumor cancers with cell therapy, reported U.S. Food and Drug Administration (FDA) accelerated approval of TECELRA (afamitresgene autoleucel) for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices (Press release, Adaptimmune, AUG 1, 2024, View Source [SID1234645277]). This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. TECELRA is the first engineered cell therapy for a solid tumor cancer approved in the U.S., and the first new therapy option in more than a decade for synovial sarcoma, a rare, soft tissue cancer that most commonly impacts young adults.

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"The approval of TECELRA is a momentous step in Adaptimmune’s journey to redefine the way cancer is treated and the culmination of a decade of groundbreaking R&D. I want to thank the patients, caregivers, investigators, and clinical teams as well as everyone at Adaptimmune and our partners who made possible this watershed moment for cell therapy and for people with synovial sarcoma. We are committed to advancing our robust clinical pipeline to serve more patients in need and plan to progress lete-cel, the next late-stage investigational treatment in our sarcoma franchise, with a rolling BLA submission to the FDA next year."

The approval of TECELRA was based on results of the SPEARHEAD-1 (Cohort 1) trial, which included 44 patients. The major efficacy outcome was overall response rate (ORR) determined by independent review and supported by duration of response. TECELRA treatment resulted in an ORR of 43% with a complete response rate of 4.5%. The median duration of response was 6 months (95% CI: 4.6, not reached). Among patients who were responsive to the treatment, 39% had a duration of response of 12 months or longer.*

Data from the pivotal SPEARHEAD-1 trial were previously published in The Lancet earlier this year.

With this approval, Adaptimmune is positioned to make a significant impact on the synovial sarcoma community. HCPs can begin testing patients, Adaptimmune systems are ready to take TECELRA orders, and an integrated support program, AdaptimmuneAssist, is available to enable a seamless and personalized experience through the treatment journey. Adaptimmune plans to have at least six to ten authorized treatment centers (ATCs) up and running this year and to onboard approximately 30 treatment centers within the first two years. These ATCs are recognized leaders in sarcoma research and treatment.

Brandi Felser, Chief Executive Officer, Sarcoma Foundation of America:

"For decades, therapeutic options for people diagnosed with synovial sarcoma have been limited. With a current five-year survival rate as low as 36%, and for those with metastatic disease at diagnosis, as low as 20%, it is long past time that synovial sarcoma patients have expanded treatment options. Since one third of patients are diagnosed under age 30, improved outcomes can have a tremendous impact. Today, there is a renewed sense of hope for this patient community."

Sandra D’Angelo, MD, Sarcoma Medical Oncologist and Cell Therapist, Memorial Sloan Kettering Cancer Center; SPEARHEAD Trial Principal Investigator:

"TECELRA (afami-cel), which uses each patient’s own immune cells to recognize and attack their cancer cells in a one-time infusion treatment, is significantly different than the current standards of care for advanced synovial sarcoma. This approval represents a much-needed new option for people diagnosed with this sarcoma and an important milestone for the use of cell therapies in solid tumor cancers."

TECELRA is contraindicated in adults who are heterozygous or homozygous for HLA-A*02:05P.

TECELRA can cause serious side effects, including cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), prolonged severe cytopenia, infections, secondary malignancies, and hypersensitivity reactions. Most common adverse reactions (incidence ≥20%) were CRS, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, edema, low white blood cells, low red blood cells and low platelets. Please see Important Safety Information, including Boxed Warning below.

Biomarker tests for human leukocyte antigens (HLA) type and melanoma-associated antigen A4 (MAGE-A4) tumor expression are required prior to treatment with TECELRA. Adaptimmune has partnered with Agilent Technologies for the development, manufacturing, and supply of a companion diagnostic for the MAGE-A4 biomarker, MAGE-A4 IHC 1F9 pharmDx, which also received approval today from the U.S. FDA and is now available. Additionally, the company partnered with Thermo Fisher Scientific to expand the labeling of Thermo Fisher’s companion diagnostic product SeCoreTM CDx HLA-A Locus Sequencing System to include TECELRA and to aid in the identification of HLA-A*02:01, A*02:02, A*02:03, and A*02:06-positive patients with synovial sarcoma.

For more information about TECELRA visit www.adaptimmune.com.

Conference Call Details

The Company will host a live webcast to provide additional details tomorrow, August 2, 8:00 a.m. EDT. A live webcast of the conference call and replay can be accessed here: View Source Call in information is as follows: 1-844-763-8274 (TOLL FREE US or Canada) or +1-647-484-8814 (International).

About Synovial Sarcoma

There are more than 50 different 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).1,2 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 approximately 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.1,3

About TECELRA

TECELRA (afamitresgene autoleucel) is a melanoma-associated antigen A4 (MAGE-A4)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices.

This indication is approved under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION: DO NOT use TECELRA in adults who are heterozygous or homozygous for HLA-A*02:05P.

BOXED WARNING: Cytokine release syndrome (CRS), which may be severe or life-threatening, occurred in patients receiving TECELRA. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care. Ensure that healthcare providers administering TECELRA have immediate access to medications and resuscitative equipment to manage CRS.

CRS

CRS occurred in 75% of patients (2% Grade ≥3) with a median onset of 2 days (range: 1 to 5 days) and median resolution of 3 days (range: 1 to 14 days). CRS (including Grade 1) was managed with tocilizumab in 55% of patients who experienced CRS.
In patients who experienced CRS, the most common symptoms included fever, tachycardia, hypotension, nausea/vomiting, and headache.
Immune Effector Cell–associated Neurotoxicity Syndrome (ICANS)

ICANS has been observed following administration of TECELRA. One patient (2%) had Grade 1 ICANS with a median onset of 2 days and resolution of 1 day.
ICANS symptoms can include mental status changes, disorientation to time and place, drowsiness, inattention, altered level of consciousness, seizures, cerebral edema, impairment of cognitive skills, progressive aphasia, and motor weakness.
Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy machinery or potentially dangerous machinery for 4 weeks following infusion due to the potential for neurologic events, including dizziness and presyncope.
Monitoring for CRS and ICANS During and Following TECELRA Infusion

Ensure that healthcare providers administering TECELRA have immediate access to medications and resuscitative equipment to manage CRS and ICANS. Ensure patients are euvolemic prior to initiating TECELRA.
During and following TECELRA administration, closely monitor patients for signs and symptoms of CRS and ICANS. Following treatment with TECELRA, monitor patients for at least 7 days at the healthcare facility. Continue to monitor patients for at least 4 weeks following treatment with TECELRA. Counsel patients to seek medical attention should signs or symptoms of CRS or ICANS occur.
At the first sign of CRS or ICANS, immediately evaluate patients for hospitalization and administer supportive care based on severity and consider further management per clinical practice guidelines.
Prolonged Severe Cytopenia

Anemia, neutropenia, and/or thrombocytopenia can occur for several weeks following lymphodepleting chemotherapy and TECELRA infusion. Patients with Grade ≥3 cytopenia not resolved by week 4 included anemia (9%), neutropenia (11%), and thrombocytopenia (5%). The median time to resolution was 7.3 weeks (range: 6.1 to 8.4 weeks) for anemia, 9.3 weeks (range: 6.4 to 12.3 weeks) for neutropenia, and 6.3 weeks (range: 6.1 to 6.4 weeks) for thrombocytopenia.
Monitor blood counts after TECELRA infusion. Manage cytopenia with growth factor and blood product transfusion according to clinical practice guidelines.
Infections

Infections may occur following lymphodepleting chemotherapy and TECELRA infusion and occurred in 32% of patients (14% Grade 3).
Do not administer TECELRA to patients with active infections and/or inflammatory disorders.
Monitor patients for signs and symptoms of infection before and after TECELRA infusion and treat patients appropriately.
Febrile neutropenia was observed in patients after TECELRA infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care, as medically indicated.
Viral reactivation has occurred in patients following TECELRA. Perform screening for Epstein-Barr virus, cytomegalovirus, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus (HIV) or any other infectious agents if clinically indicated. Consider antiviral therapy to prevent viral reactivation per local guidelines.
Secondary Malignancies

Patients treated with TECELRA may develop secondary malignancies or recurrence of their cancer. Monitor for secondary malignancies.
Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, may occur due to dimethyl sulfoxide (DMSO) in TECELRA. Observe patients for hypersensitivity reactions during infusion.
Potential for HIV Nucleic Acid Test False-Positive Results

The lentiviral vector used to make TECELRA has limited, short spans of genetic material that are identical to HIV. Therefore, some commercial HIV nucleic acid tests may yield false-positive results in patients who have received TECELRA.
Adverse Reactions

Most common adverse reactions (incidence ≥20%) are CRS, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, abdominal pain, non-cardiac chest pain, decreased appetite, tachycardia, back pain, hypotension, diarrhea, and edema.
Most common Grade 3 or 4 laboratory abnormalities (incidence ≥20%) were lymphocyte count decreased, neutrophil count decreased, white cell blood count decreased, red blood cell decreased, and platelet count decreased.
Most common serious adverse reactions (≥5%) were CRS and pleural effusion.
Please see full Prescribing Information, including Boxed Warning and Medication Guide.

On August 1, 2024 GSK plc (LSE/NYSE: GSK) reported the US Food and Drug Administration (FDA) has approved Jemperli (dostarlimab) in combination with carboplatin and paclitaxel (chemotherapy) followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer (Press release, GlaxoSmithKline, AUG 1, 2024, View Source [SID1234645260]). This approval broadens the previous indication for Jemperli plus chemotherapy to include patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumours who represent 70-75% of patients diagnosed with endometrial cancer and who have limited treatment options. The supplemental Biologics License Application (sBLA) supporting this expanded indication received Priority Review and was approved ahead of the Prescription Drug User Fee Act action date.

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Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "Jemperli plus chemotherapy is the first and only immuno-oncology regimen to show significant and meaningful improvement in overall survival for adult patients with primary advanced or recurrent endometrial cancer regardless of biomarker status. We are thrilled this option is now available for more patients in the US, including the 70-75% with MMRp/MSS tumours where treatment options have been limited."

Today’s expanded approval is based on results from dual primary endpoints of investigator-assessed progression-free survival (PFS) and overall survival (OS) from Part 1 of the RUBY phase III trial. RUBY Part 1 is the only clinical trial in this setting to show a statistically significant OS benefit in the full population of patients with primary advanced or recurrent endometrial cancer, demonstrating a 31% reduction in risk of death (HR: 0.69; 95% CI: 0.54–0.89) compared to chemotherapy alone.

At the 2.5-year landmark, 61% (95% CI: 54-67) of patients in the Jemperli plus chemotherapy group compared to 49% (95% CI: 43-55) in the chemotherapy group were alive. In addition, a 16.4-month improvement in median OS was observed with Jemperli plus chemotherapy versus chemotherapy alone (44.6 months [95% CI: 32.6–NR] vs. 28.2 months [95% CI: 22.1–35.6], respectively). The median duration of follow-up was more than three years.1 The safety and tolerability analysis from RUBY Part 1 showed a safety profile for Jemperli and carboplatin-paclitaxel that was generally consistent with the known safety profiles of the individual agents. The most common treatment-emergent adverse events (≥ 20%) in patients receiving Jemperli plus chemotherapy were nausea, alopecia, fatigue, peripheral neuropathy, anaemia, arthralgia, constipation, diarrhoea, myalgia, rash, hypomagnesemia, decreased appetite, peripheral sensory neuropathy and vomiting.

Matthew Powell, MD, Chief, Division of Gynecologic Oncology, Washington University School of Medicine, and US principal investigator of the RUBY trial said: "The initial approval of Jemperli plus chemotherapy was practice-changing for patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer and today’s expanded approval will offer even more patients the opportunity for improved outcomes. This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer."

Adrienne Moore, Survivor, Founding Member and President of Endometrial Cancer Action Network for African-Americans (ECANA) said: "With this expanded approval for Jemperli plus chemotherapy, GSK is bringing a much-needed new treatment regimen to the endometrial cancer community that may help patients with primary advanced or recurrent endometrial cancer live longer, providing hope to patients and their families. Survivors and advocates should be excited by today’s news and especially delighted that this approval means that more patients in the US who are diagnosed with endometrial cancer will have a new treatment option."

About endometrial cancer
Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. Endometrial cancer is the most common gynaecologic cancer in developed countries,2 with an estimated 1.6 million people living with active disease at any stage and 417,000 new cases reported each year worldwide.3 Incidence rates are expected to rise by approximately 40% between 2020 and 2040.4 Approximately 15-20% of patients with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.5 Among patients with primary advanced or recurrent endometrial cancer, approximately 70-75% have MMRp/MSS tumours.6

About RUBY
RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo.

In Part 1, the dual-primary endpoints are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS. The statistical analysis plan included pre-specified analyses of PFS in the mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and overall populations and OS in the overall population. Pre-specified exploratory analyses of PFS and OS in the MMRp/MSS population and OS in the dMMR/MSI-H populations were also performed. RUBY Part 1 included a broad population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma.

In Part 2, the primary endpoint is investigator-assessed PFS in the overall population, followed by PFS in the MMRp/MSS population, and OS in the overall population is a key secondary endpoint. Additional secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.

RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organisation dedicated to transforming the standard of care in gynaecologic oncology.

About Jemperli (dostarlimab)
Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development programme. A robust clinical trial programme includes studies of Jemperli alone and in combination with other therapies in gynaecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes.

In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This includes patients with MMRp/MSS and dMMR/MSI-H tumours. Jemperli is also approved as a single agent for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. Additionally, Jemperli is indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli and cobolimab (GSK4069889), a TIM-3 antagonist.

Please see accompanying US Prescribing Information.

On August 1, 2024 Daiichi Sankyo (TSE: 4568) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the first patient has been dosed in the IDeate-Lung02 Phase 3 trial evaluating the efficacy and safety of investigational ifinatamab deruxtecan (I-DXd) in patients with relapsed small cell lung cancer (SCLC) versus treatment of physician’s choice of chemotherapy (Press release, Merck & Co, AUG 1, 2024, View Source [SID1234645278]).

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Ifinatamab deruxtecan is a specifically engineered potential first-in-class B7-H3 directed DXd antibody-drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Merck.

Small cell lung cancer is the second most common type of lung cancer, accounting for about 15% of cases. SCLC is aggressive and progresses rapidly to the metastatic stage, which has a five-year survival rate of only 3%. Approximately 65% of all SCLC tumors have a moderate-to-high expression of the protein B7-H3, which is associated with disease progression and poor prognosis.

"Patients living with small cell lung cancer face poor outcomes with currently available treatments," said Mark Rutstein, MD, global head, oncology clinical development, Daiichi Sankyo. "The IDeate-Lung02 trial is an important next step as we look to better understand the role of ifinatamab deruxtecan as a potential new medicine for patients with certain types of small cell lung cancer."

"The initiation of the IDeate-Lung02 trial for ifinatamab deruxtecan marks the second pivotal study since the start of our collaboration with Daiichi Sankyo and follows the recent initiation of the REJOICE-Ovarian01 Phase 2/3 study for raludotatug deruxtecan," said Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "This is a significant milestone as we work together to evaluate an innovative medicine that may have the potential to make a meaningful difference in the lives of people facing small cell lung cancer, a difficult-to-treat cancer."

The initiation of IDeate-Lung02 is based on updated results from a subgroup analysis of the IDeate-PanTumor01 Phase 1/2 trial of ifinatamab deruxtecan presented at the 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer.

About the IDeate-Lung02 trial

IDeate-Lung02 is a global, multicenter, randomized, open-label Phase 3 trial evaluating the efficacy and safety of ifinatamab deruxtecan (I-DXd) versus treatment of physician’s choice of chemotherapy (amrubicin, lurbinectedin or topotecan) in patients with relapsed SCLC following disease progression with only one prior line of platinum-based chemotherapy. Eligible patients will be randomized to receive ifinatamab deruxtecan (12 mg/kg) or physician’s choice of chemotherapy.

The dual primary endpoints are objective response rate (ORR) as assessed by blinded independent central review (BICR) and overall survival. Secondary endpoints include ORR as assessed by investigator, and progression-free survival, duration of response, disease control rate and time to response – all assessed by both BICR and investigator.

IDeate-Lung02 is expected to enroll approximately 460 patients across Asia, Europe, Oceania, North America and South America. For more information, please visit ClinicalTrials.gov.

About small cell lung cancer

More than 2.48 million lung cancer cases were diagnosed globally in 2022. Small cell lung cancer is the second most common type of lung cancer, accounting for about 15% of cases. SCLC is aggressive and progresses rapidly to the metastatic stage, which has a five-year survival rate of only 3%. While conventional first-line therapy for patients with advanced SCLC may help some patients live longer, the current second-line standard of care offers limited clinical benefit and new treatment approaches are needed.

About B7-H3

B7-H3 is a transmembrane protein that belongs to the B7 family of proteins which bind to the CD28 family of receptors that includes PD-1. B7-H3 is overexpressed in a wide range of cancer types, including small cell lung cancer, and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target. There are currently no B7-H3 directed medicines approved for the treatment of any cancer.

About ifinatamab deruxtecan

Ifinatamab deruxtecan (I-DXd) is an investigational, potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Ifinatamab deruxtecan is being evaluated in a global development program, which includes IDeate-Lung02, a Phase 3 trial in patients with relapsed SCLC versus investigator’s choice of chemotherapy, IDeate-Lung01, a Phase 2 monotherapy trial in patients with previously treated extensive-stage SCLC and IDeate-PanTumor01, a Phase 1/2 first-in-human trial in collaboration with Sarah Cannon Research Institute (SCRI) with study operational oversight and delivery provided through SCRI’s early phase oncology clinical research organization, SCRI Development Innovations in Nashville, TN. Ifinatamab deruxtecan was granted orphan drug designation by the U.S. Food and Drug Administration in April 2023 and by the European Commission in February 2024 for the treatment of SCLC.

On August 1, 2024 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on its Phase III clinical trial, FLAMINGO-01, which is evaluating GLSI-100, an immunotherapy to prevent breast cancer recurrences, reported the following update of the expansion of clinical sites into Spain (Press release, Greenwich LifeSciences, AUG 1, 2024, View Source [SID1234645239]).

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As previously announced, the Company has partnered with GEICAM, the largest academic breast cancer research network in Spain, where 38 hospitals have agreed to participate in FLAMINGO-01.

To date, approximately 30 out of 38 sites have conducted site initiation visits (SIVs). An SIV is followed by site activation, HLA type screening, and study treatment. To date approximately 19 sites have been activated. Multiples sites have begun screening patients for HLA type and have started treating patients. The Company has visited and trained in-person at approximately 26 out of the 38 sites to ensure optimal treatment at each site. In the coming months, GEICAM hopes to complete the remaining SIVs and the Company hopes to visit the remaining sites.

"It has been an honor to meet with the excellent study staff, investigators and GEICAM staff across Spain. Their expertise and interest in FLAMINGO-01 is encouraging for the success of the study. We look forward to seeing patient recruitment increase in Spain as other countries in the European Union become active," remarked Jaye Thompson, VP of Clinical and Regulatory Affairs.

CEO Snehal Patel commented, "The remarkable progress in Spain, in just May through July, is a testament to the commitment of GEICAM and our team to collaborate and to train the sites together, which we hope will lead to high quality treatment of patients. With just these 30 sites, we have approximately doubled the number of sites that we have opened in the US."

The Company may provide updates on the status of other countries in Europe as the clinical trial is expanded to up to 150 sites in the US, Spain, Italy, France, Germany, and Poland.

About GEICAM

Founded in 1995, GEICAM is a not-for-profit organization leading academic breast cancer research in Spain. It has conducted more than 140 studies involving more than 67,000 women and men and is comprised of more than 900 experts based in over 200 Spanish hospitals. Its mission is to promote independent clinical, epidemiological, and translational research in oncology, with a multidisciplinary approach and under quality criteria, to improve health outcomes, as well as prevention, medical education, and the dissemination of the knowledge of this disease to patients and general society. More information on GEICAM can be found at View Source

About FLAMINGO-01 and GLSI-100

FLAMINGO-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2 positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial is led by Baylor College of Medicine and currently includes US clinical sites from university-based hospitals and cooperative networks with plans to expand into Europe and to open up to 150 sites globally. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients will be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types will be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater.

For more information on FLAMINGO-01, please visit the Company’s website here and clinicaltrials.gov here. Contact information and an interactive map of the majority of participating clinical sites can be viewed under the "Contacts and Locations" section. Please note that the interactive map is not viewable on mobile screens. Related questions and participation interest can be emailed to: [email protected]

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 300,000 new breast cancer patients and 4 million breast cancer survivors. HER2 (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

On August 1, 2024 Instil Bio, Inc. (Nasdaq: TIL, "Instil") and ImmuneOnco Biopharmaceuticals (Shanghai) Inc. (HKEX Code: 1541.HK, "ImmuneOnco"), reported a definitive agreement pursuant to which Instil is in-licensing ex-China development and commercial rights to ImmueOnco’s proprietary PD-L1xVEGF bispecific antibody, IMM2510, as well as its next-generation anti-CTLA-4 antibody, IMM27M (Press release, Instil Bio, AUG 1, 2024, View Source [SID1234645261]).

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IMM2510 is a novel, potentially best-in-class bispecific antibody consisting of an anti-PD-L1 antibody fused to a vascular endothelial growth factor (VEGF) receptor "trap" which binds VEGF. IMM2510 is differentiated from other PD(L)1xVEGF antibodies by its ability to bind multiple VEGF receptor ligands beyond VEGF-A, a smaller molecular weight allowing for potentially better tumor penetration, and enhanced antibody-dependent cellular cytotoxicity (ADCC) designed to improve tumor killing. IMM2510 has completed a dose-escalation clinical trial for advanced solid tumors and demonstrated multiple responses including patients with squamous non-small cell lung cancer (NSCLC) who previously failed PD-1 inhibitors.

IMM27M is a next-generation anti-CTLA-4 antibody with enhanced ADCC activity, which has been designed to promote intratumoral regulatory T cell depletion to enhance the efficacy and reduce the toxicity associated with first-generation anti-CTLA-4 antibodies. IMM27M has completed a dose-escalation clinical trial demonstrating anti-tumor activity in patients with advanced solid tumors and has entered combination studies with IMM2510 in China in July 2024.

Terms of License and Collaboration Agreement
Under the terms of the agreement, a wholly owned subsidiary of Instil will receive global development and commercialization rights for IMM2510 and IMM27M outside of Greater China, while ImmuneOnco will retain development and commercialization rights in Greater China including Taiwan, Macau, and Hong Kong. ImmuneOnco will receive an upfront payment and potential near-term payments of up to $50 million as well as potential additional development, regulatory, and commercial milestones exceeding $2 billion plus single digit to low double-digit percentage royalties on global ex-China sales.