On December 6, 2021 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on the development of GP2, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery, reported that manufacturing and clinical updates on Phase III clinical trial FLAMINGO-01 (Press release, Greenwich LifeSciences, DEC 6, 2021, View Source [SID1234596500]).

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Over the past six months, the Company has been actively selecting and contracting partners to manufacture clinical and commercial lots of GP2 and to manage the Phase III clinical trial. An update on these activities follows:

Today, the Company ran its first commercial fill line of GP2 at its fill and finish partner’s production facility with sufficient scale to produce up to 80,000 doses of GP2 per lot. Three commercial lots of GP2 will be required to file a Biologics License Application (BLA) for GP2. The three lots combined should treat approximately 22,000 patients, and in the initial GP2 indication, approximately 17,000 new patients could be treated per year, saving up to 1,500 to 2,000 lives per year.
Clinical research organization (CRO) has been engaged to manage the Phase III clinical trial.
GP2 active ingredient manufacturer has been engaged to produce commercial scale GP2 lots.
Commercial testing laboratory has been engaged to release clinical and commercial GP2 lots and to manage GP2 stability program.
In addition to their operational role, these partners will play a key role in preparing the manufacturing and clinical information necessary to submit a BLA upon a successful interim analysis of the Phase III clinical trial.
Partners for HLA typing, blood test collection, GP2 storage and distribution, GM-CSF distribution, immune response testing, and blood sample storage have been selected to support the Phase III clinical trial.
CEO Snehal Patel commented, "Commencing commercial scale manufacturing is a major milestone for the Company. We are carefully selecting partners who are leaders in the industry with whom we hope to work with over the long term. At the same time, the Company is developing a back-up strategy by location and function to reduce risk and provide multiple options going forward. In addition, all of the various parties required to operate the Phase III clinical trial testing, storage, and distribution activities have been integrated well through our management team and CRO. The expertise of our partners has served to enhance the quality and accelerate the progress of our manufacturing and clinical plans."

About FLAMINGO-01 and GLSI-100

The Phase III clinical trial will be called FLAMINGO-01 and the combination of GP2 + GM-CSF will be called GLSI-100. The Phase III trial is comprised of 2 blinded, randomized, placebo-controlled arms for approximately 500 HLA-A*02 patients and 1 open label arm of up to 100 patients for all other HLA types. An interim analysis has been designed to detect a hazard ratio of 0.3 in IDFS, 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. The trial is currently being registered on clinicaltrials.gov and the link and trial identifier will be published shortly. For future updates about FLAMINGO-01 please visit the Company’s clinical trial tab at View Source

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 282,000 new breast cancer patients and 3.8 million breast cancer survivors in 2021. HER2/neu (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 6 December 2021 Immunocore Holdings Plc (Nasdaq: IMCR), a late-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infectious and autoimmune disease, reported the initial Phase 1 data of IMC-C103C, a bispecific T cell engager targeting MAGE-A4, in selected advanced solid tumors (Press release, Immunocore, DEC 6, 2021, View Source [SID1234596499]).

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IMC-C103C was developed using the company’s innovative ImmTAC technology platform and is being developed in partnership with Genentech, a member of the Roche Group. The trial (IMC-C103C-101) includes a Phase 1 dose escalation to evaluate safety, maximum tolerated dose / expansion dose, and preliminary clinical activity. The initial Phase 1 data from this study is the subject of a presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress.

The presentation includes data from 44 patients enrolled across 10 dose-escalation cohorts. Indications with high MAGE-A4 prevalence (eg. serous ovarian, synovial sarcoma) enrolled all-comers with retrospective MAGE-A4 testing by immunohistochemistry (IHC) while other indications required prospective confirmation of tumor MAGE-A4 expression by IHC.

IMC-C103C demonstrated a manageable safety profile. The most common any-grade, treatment-related adverse events were consistent with cytokine release syndrome, were dose dependent and rapidly resolved. The most common related grade 3 or grade 4 adverse event was neutropenia, typically at doses ≥ 90 micrograms. Neutropenia was reversible, with treatment interruption or G-CSF, and was not dose-limiting. None of the treatment-related AEs led to discontinuation or death.

IMC-C103C dose escalation began at 0.5 micrograms, the minimum anticipated biological effect level (MABEL), and includes 10 cohorts to date. Pharmacodynamic biomarkers of T cell activation were first observed at 15 micrograms and became consistent and robust at doses ≥ 90 micrograms. IMC-C103C treatment results in a substantial increase in T cell infiltration in tumor biopsies relative to baseline.

The most frequently enrolled patients had platinum relapsed/refractory ovarian cancer, who were enrolled regardless of their tumor MAGE-A4 protein expression. Most of these patients had low or no MAGE-A4 protein expression in their tumors as measured by IHC (median H score = 8). One ovarian cancer patient, with a very low MAGE protein expression, treated at a dose of < 90 micrograms, had a durable confirmed partial response (PR) with 8.3 months duration. An additional ovarian cancer patient at a dose of ≥ 90 micrograms, also with very low MAGE-A4 protein expression, has a confirmed partial response ongoing at 4.4+ months. One of the three non-ovarian cancer patients (head and neck squamous cell carcinoma) at a dose of ≥ 90 micrograms has a confirmed PR that is ongoing.

"IMC-C103C is our second T cell engager to demonstrate durable clinical activity, now in multiple solid tumors," stated Bahija Jallal, Chief Executive Officer. "We are highly encouraged to see these responses in ovarian and head and neck cancer. The durable PRs in ovarian cancer occur in heavily pre-treated patients even with low MAGE-A4 protein tumor expression. We have initiated an expansion arm in ovarian carcinoma, while we continue signal searching and determining the optimal dose in multiple solid tumors."

Earlier this month, Immunocore initiated an expansion arm in high grade serous ovarian carcinoma at 140 micrograms. IMC-C103C-101 will continue to explore the optimal dose and evaluate clinical activity in multiple solid tumors. The company plans to present additional data from this program in 2022. IMC-C103C is part of a co-development / co-promotion collaboration with Genentech under which Immunocore shares program costs and profits equally.

Conference Call Information
Immunocore will host a live webcast and conference call today beginning at 8:00 am E.T. to discuss the results with Dr. Diwakar Davar, an assistant professor of medicine and a medical oncologist and hematologist at the University of Pittsburgh Medical Center (UPMC). A live webcast of the conference call will be available under "Events" in the Investor Relations section of Immunocore Holdings’ website at www.immunocore.com. The presentation from today’s call and the archived webcast will be available on Immunocore’s website after the conference call concludes and will be available for 30 days following the call.

On December 6, 2021 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported that it has submitted its New Drug Application (NDA) for poziotinib to the U.S. Food and Drug Administration (FDA) for use in patients with previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) with HER2 exon 20 insertion mutations (Press release, Spectrum Pharmaceuticals, DEC 6, 2021, View Source [SID1234596498]). The NDA submission is based on the positive results of Cohort 2 from the ZENITH20 clinical trial, which assessed the safety and efficacy of poziotinib. The product has received Fast Track designation and there is currently no treatment specifically approved by the FDA for this indication.

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"The NDA submission for poziotinib marks an important step in achieving a first treatment for patients with HER2 exon 20 insertion mutations in lung cancer," said Joe Turgeon, President and CEO of Spectrum Pharmaceuticals. "I want to thank the patients, investigators and our internal staff who have passionately worked to achieve this important milestone in an area of high unmet medical need."

ZENITH20 Cohort 2 Clinical Results Summary

Results for Cohort 2 of the ZENITH20 clinical trial have been published in the Journal of Clinical Oncology (November 29, 2021), and can be accessed by clicking here.

Cohort 2 enrolled 90 patients who received an oral once daily dose of 16 mg of poziotinib. The intent-to-treat analysis demonstrated a confirmed objective response rate (ORR) of 27.8% (95% Confidence Interval (CI), 18.9%-38.2%). The observed lower bound of 18.9% exceeded the pre-specified lower bound of 17%. The median duration of response was 5.1 months and the median progression free survival was 5.5 months. In this cohort, 87% of patients had drug interruptions with 11 patients (12%) permanently discontinuing due to adverse events. 13 patients (14%) had treatment-related serious adverse events. As previously announced, the company had a successful pre-NDA meeting with the FDA which resulted in an agreement to submit an NDA for poziotinib. During the meeting, Spectrum confirmed with the FDA that Cohort 2 data could serve as the basis of an NDA submission. The company will continue to work with the FDA as appropriate, while the agency conducts its review.

About the ZENITH20 Clinical Trial

The ZENITH20 study consists of seven cohorts of NSCLC patients. Cohorts 1 (EGFR) and 2 (HER2) in previously treated NSCLC patients with exon 20 mutations and Cohort 3 (EGFR) in first-line patients have completed enrollment. Cohort 4 (HER2) in first-line NSCLC patients with exon 20 mutations is still enrolling patients. Cohorts 1- 4 are each independently powered for a pre-specified statistical hypothesis and the primary endpoint is objective response rate (ORR). Cohort 5 includes previously treated or treatment-naïve NSCLC patients with EGFR or HER2 exon 20 insertion mutations. Cohort 6 includes NSCLC patients with classical EGFR mutations who progressed while on treatment with first-line osimertinib and developed an additional EGFR mutation. Cohort 7 includes NSCLC patients with a variety of less common mutations in EGFR or HER2 exons 18-21 or the extracellular or transmembrane domains.

On December 6, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported it will hold a conference call to discuss the data being presented at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, being held between December 11-14, 2021 (Press release, Autolus, DEC 6, 2021, View Source [SID1234596497]). Note this is a change to the timing announced previously.

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New timing of investor call

Management will host a conference call and webcast on Monday, December 13, 2021, at 8:00 am ET/1:00 pm GMT to discuss the ASH (Free ASH Whitepaper) data. To listen to the webcast and view the accompanying slide presentation, please go to the events section of Autolus’ website.

On December 6, 2021 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported that clinical data on MCLA-145 from the phase 1 trial in patients with solid tumors at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress 2021 being held virtually (Press release, Merus, DEC 6, 2021, View Source [SID1234596496]).

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"We are encouraged by the progress we are making with MCLA-145," said Dr. Andrew Joe, Chief Medical Officer. "Patients have been treated at 8 dose levels with preliminary evidence of antitumor activity observed, as we continue to explore MCLA-145 as monotherapy."

MCLA-145

The reported data are from the phase 1 open-label, multicenter dose escalation study, of bispecific antibody MCLA-145 in patients with solid tumors. The primary objective is to evaluate the safety, tolerability, and dose-limiting toxicity (DLT) of MCLA-145 and to determine maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE).

Observations in the presentation include:

As of the data cutoff date of July 14, 2021, 34 patients with advanced or metastatic solid tumors with median age of 60.5 (range 27-81) years have been treated at 8 dose levels ranging from 0.4-75mg Q2W
Median (range) duration of treatment with MCLA 145 was approximately 6 (1–74) weeks
Reported adverse events (AEs) have been managed with drug interruption and/or administration of steroids in some patients
Treatment-emergent AEs (TEAEs) occurred in 33 patients (97.1%); treatment-related TEAEs occurred in 23 patients (67.6%), most commonly fatigue (n=6, 17.6%) and decreased neutrophil count (n=6, 17.6%)
DLTs defined as within 28 days from the first infusion occurred in 4 patients (11.8%)
Laboratory alanine transaminase/aspartate transaminase (ALT/AST) elevations of any grade were observed in 15 patients (44.1%), with grade ≥3 ALT/AST elevations in 6 patients (17.6%)
Preliminary evidence of antitumor activity has been observed at doses ≥25 mg biweekly
Peripheral blood shows robust T-cell activation, including activation of cytotoxic CD8+ cells and cytokines, across the 10 to 75 mg biweekly dosing range
Further evaluation of optimal dose and efficacy in PD-L1+ tumors is planned.
The phase 1 clinical trial of MCLA-145 consists of a dose escalation phase, followed by a planned dose expansion phase. MCLA-145 is the first drug candidate co-developed under Merus’ global collaboration and license agreement with Incyte, which permits the development and commercialization of up to 11 bispecific and monospecific antibodies from the Merus Biclonics platform. Merus retains full rights to develop and commercialize MCLA-145, if approved, in the United States; and Incyte holds full rights to develop and commercialize MCLA-145 outside the United States.