On September 20, 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 that new data from the Company’s lead program, tebentafusp (IMCgp100), at an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Immunocore, SEP 20, 2021, View Source [SID1234590903]).

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The findings presented by Alexander N. Shoushtari MD, medical oncologist at Memorial Sloan Kettering Cancer Center, demonstrated that reduction by Week 9 in circulating tumor DNA (ctDNA) while on tebentafusp is strongly associated with overall survival (OS). A majority (70%) of evaluable patients had any ctDNA reduction while 5% of patients had radiographic response per the RECISTv1.1 criteria. In addition, 14% of patients had complete ctDNA clearance and long OS; this included some patients with best response of stable or progressive disease. The analysis was based on the phase 2 trial of tebentafusp in HLA-A*02:01 positive, previously treated patients with metastatic uveal melanoma (mUM) (IMCgp100-102).

"Uveal melanoma is characterized by a defined set of unique mutations that can be measured in the blood as free circulating tumor DNA," said David Berman, Immunocore’s Head of Research and Development, "We found that the degree of ctDNA reduction from tebentafusp was strikingly correlated with overall survival. This association was observed even in patients whose tumor lesions appeared radiographically stable or progressing and suggests that clinical benefit from tebentafusp may occur even in patients who did not have a RECIST response."

The U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the United Kingdom’s Medicines and Healthcare Products Regulatory Agency (MHRA) have each accepted applications seeking the approval of tebentafusp for the treatment of HLA-A*02:01-positive ad

On September 20, 2021 Boston Scientific Corporation (NYSE: BSX) reported the EPOCH clinical trial of the TheraSphere Y-90 Glass Microspheres (TheraSphere treatment) successfully met both primary endpoints, including progression-free survival (PFS) and hepatic progression-free survival (hPFS) of patients with metastatic colorectal cancer (mCRC) of the liver. In the trial, TheraSphere treatment – a selective internal radiation therapy (SIRT) comprised of microscopic glass beads containing radioactive yttrium (Y-90) that are specifically delivered to target tumors – was used as a second-line treatment in combination with standard of care systemic chemotherapy (SOC) for patients who had disease progression during or after first-line chemotherapy. The clinical findings were presented today as late-breaking data at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 and will be published in the Journal of Clinical Oncology.

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"The EPOCH trial not only demonstrated positive safety and efficacy data for the patients treated in this study, but underscores the success of integrating a device-based therapy like TheraSphere treatment in the continuum of care with systemic chemotherapy and biologic regimens, thereby providing the rationale and setting the stage for future investigation in other cancer types," said Riad Salem, M.D., M.B.A, interventional radiologist at Northwestern Memorial Hospital and co-principal investigator of the EPOCH trial.i

TheraSphere Vial and Sphere ID

TheraSphere Vial and Sphere ID
An estimated 1.9 million global cases of colorectal cancer (CRC) are diagnosed each year, making it the third most common cancer worldwide.ii Approximately one third of all patients with CRC present with, or subsequently develop, metastases in the liver (liver dominant mCRC).iii Patients with mCRC are most commonly treated with surgery and systemic chemotherapy, a therapy that targets the entire body. TheraSphere treatment, indicated for use in patients with hepatic neoplasia/malignancies including liver dominant mCRC in Canada, Europe and regions of Asia, delivers Y-90 directly to liver tumors via catheter, which minimizes radiation exposure to surrounding healthy tissue.

"EPOCH is the first positive phase 3 SIRT trial in any disease setting and the data is expected to support our regulatory submission to the U.S. FDA, with the hope that more patients with liver dominant mCRC will gain access to TheraSphere as a treatment option in the future," said Peter Pattison, president, Interventional Oncology, Peripheral Interventions, Boston Scientific.

The global, prospective EPOCH pivotal clinical trial is a phase 3 study, designed to assess therapeutic benefit compared to SOC, which randomized 428 patients with mCRC to second line chemotherapy, with or without the addition of TheraSphere treatment. Both primary endpoints were met and included progression-free survival and hepatic progression-free survival, which reflect how long patients live without the disease progressing further, both systemically and within the liver. The addition of TheraSphere treatment significantly increased both PFS (p=0.0013) and hPFS (p<0.0001). Patients receiving TheraSphere treatment with second-line chemotherapy were 31% less likely to show disease progression or death (HR = 0.69) and 41% less likely to show hepatic disease progression or death versus with chemotherapy alone (HR = 0.59).

"In the second line of therapy for metastatic colorectal cancer, with disease isolated to the liver, the addition of TheraSphere with chemotherapy resulted in a significant delay in overall tumor progression," said Mary F. Mulcahy, M.D., medical oncologist at Northwestern Memorial Hospital and co-principal investigator of the EPOCH trial.i "Additionally, chemotherapy-related adverse events were comparable between the trial arms."

Earlier this year, the U.S. FDA approved TheraSphere for the treatment of unresectable hepatocellular carcinoma (HCC) and granted Breakthrough Device Designation for expedited review as a treatment of patients with glioblastoma, an aggressive type of cancer that can occur in the brain or spinal cord. It is the only radioembolization technology in the U.S. indicated for unresectable HCC.

CAUTION: In the U.S., the use of TheraSphere for mCRC is for investigational use only as the safety and effectiveness have not been established.

For more information on TheraSphere treatment, visit www.therasphere.com.

On September 20, 2021 Oncocyte Corporation (Nasdaq: OCX), a precision diagnostics and monitoring company with the mission to improve patient outcomes by providing clear insights that inform critical decisions in the diagnosis, treatment, and monitoring of cancer, reported that new data in an oral presentation at the European Society for Medical Oncology Congress (ESMO) (Free ESMO Whitepaper) 2021 evaluating DetermaIO as a biomarker for immune therapy response (Press release, Oncocyte, SEP 20, 2021, View Source [SID1234587980]). The results demonstrated in a randomized clinical trial setting that DetermaIO, a 27-gene precision diagnostic, is predictive of response to neoadjuvant immune checkpoint inhibitor treatment of triple negative breast cancer (TNBC), and support the potential of DetermaIO to serve as a precision diagnostic for this important class of novel therapies with expanding indications across tumor types.

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Commenting on the trial results, Ron Andrews, Chief Executive Officer of Oncocyte, stated, "Demonstrating the utility of DetermaIO in the rigorous setting of a randomized, therapeutic clinical trial is a landmark accomplishment for Oncocyte, and simply put, we are very enthusiastic about the results. These data from a prestigious international clinical trial provide important confirmation of DetermaIO’s capacity to work as a precision diagnostic across the checkpoint inhibitor class of therapies which we believe can benefit both drug development and add precision to patient treatment decisions. We are thrilled to add this new data to the compelling collection of studies that validate the assay’s utility in Lung, TNBC, and Bladder cancers, and across four approved immunotherapies – Keytruda, Opdivo, Tecentriq and Imfinzi – suggesting a potential pan-cancer and pan-immunotherapy utility in both primary and metastatic settings. We look forward to advancing DetermaIO toward clinical launch in Q4, allowing us access to a US market estimated at three billion dollars."

Key results and conclusions from the late breaking oral presentation titled, "Predictive value of gene-expression profiles (GEPs) in the Neo TRIPaPDL1 trial", include:

The utility of DetermaIO (IO Score) was evaluated as part of the NeoTRIPaPDL1 (NCT02620280) study, an international clinical trial that enrolled 241 Stage I-III TNBC patients from seven countries across Europe and Asia, and randomized them into two study arms: neoadjuvant treatment with chemotherapy or with chemotherapy in combination with an immunotherapy
A key goal for DetermaIO was to assess its utility as a predictive diagnostic for immune therapy, a successful result for a precision diagnostic shows that patients benefit only in the combination of a positive test and receiving the specific immunotherapy (IO score and atezolizumab in this study)
In the group of IO score positive patients who received both immunotherapy and chemotherapy, response rates were substantially higher compared to those who received chemotherapy alone (71% versus 51%)
Conversely, in the IO score negative population, no significant difference in response rates was seen (40% versus 44%)
The IO score positive patients who received atezolizumab demonstrated a predictive response at least 20% higher than the other three groups and was statistically significant as measured by an interaction test (p = 0.029)
42.7% of the patients were IO score positive demonstrating that the test is identifying a substantial subset of TNBC patients who may benefit from immune checkpoint therapy
Taken together, these data demonstrate the potential of DetermaIO to be a precision diagnostic to identify both responders and non-responders to immunotherapy. This shows its potential to inform the selection of patients who will benefit from treatment while also helping to avoid treatment associated toxicities for those who will not benefit.
Giampaolo Bianchini, M.D., Head of the Breast Cancer Group at the San Raffaele Scientific Institute, and trial investigator said, "Looking at pathologic complete response in this prospectively, randomized Phase III trial, IO score demonstrated the ability to identify those TNBC patients who benefitted the most from the addition of atezolizumab, and this was supported statistically by a significant test of interaction. Notably, we assessed more than 80 immune-related signatures and none of them showed similar significant tests of interaction. In addition, IO score was significantly more associated with pCR in atezolizumab arm than any other immune-related signatures. This observation underscores the capability of the test to measure features across the tumor microenvironment, including those intrinsic to the tumor (mesenchymal features) and extrinsic to the tumor such as immune infiltration."

Rob Seitz, Head of Immune Oncology at Oncocyte, said, "One of the most common questions we get from experts in the immune oncology field is how does DetermaIO compare to other immune related signatures. The additional research of Dr. Bianchini’s group showed that the IO score clearly distinguished itself from the numerous immune related signatures that were tested, a result that demonstrates DetermaIO has a unique and pivotal role versus other tests in selecting patients for immunotherapy. This is an extremely important milestone, where for the first time, by evaluating the tumor micro environment or TME, we have a precision diagnostic for immunotherapy that can find the right treatment for the right patient with specificity for response."

On Tuesday, September 28th, 2021 from 1-2PM EST, the Company will be hosting a Key Opinion Leader event with Dr. Bianchini and Priyanka Sharma, M.D., Professor of Medicine at the University of Kansas Medical Center to discuss the unmet need for identifying patients with triple-negative breast cancer (TNBC) who will respond to immunotherapy, with Dr. Bianchini highlighting the NeoTRIPaPDL1 randomized clinical trial ESMO (Free ESMO Whitepaper) data.

Abstract and Presentation Details:

Title: Predictive value of gene-expression profiles (GEPs) in the Neo TRIPaPDL1 trial
Abstract #: LBA12
Session type: Late-breaking abstract and oral presentation
Presenter: Bianchini, G.
Authors: Bianchini, G., et al.
Date and time: September 20, 2021, 17:30 CET
About The NeoTRIPaPDL1 Study

The NeoTRIPaPDL1 (NCT02620280) study is an international clinical trial comprising patients from seven countries across Europe and Asia which randomized TNBC patients into two treatment arms: treatment with chemotherapy or treatment with chemotherapy in combination with an immunotherapy. 241 patients with Stage I-III triple negative breast cancer were randomized to either receive immunotherapy plus chemotherapy, or standard of care chemotherapy, prior to their surgery (the neoadjuvant setting). The trial investigators have previously reported initial response data describing how the patient responded with the strongest response being no evidence of the tumor at the time of surgery (pathologic complete response or pCR).

On September 20, 2021 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported positive topline results from the potentially registration-enabling cohort of the Phase 2 KRYSTAL-1 study, evaluating adagrasib in patients with advanced non-small cell lung cancer (NSCLC) harboring the KRASG12C mutation following prior systemic therapy (Press release, Mirati, SEP 20, 2021, View Source [SID1234588009]).

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The analysis was completed in the intent-to-treat population, which showed adagrasib 600mg BID demonstrated an objective response rate (ORR) of 43% and a disease control rate of 80%, based on central independent review as of June 15, 2021. The median follow-up was 9 months. Importantly, 98.3% of patients received adagrasib following treatment with immunotherapy and chemotherapy. The safety and tolerability profile was consistent with previously reported findings for adagrasib in patients with advanced NSCLC.

The Company plans to submit detailed results from the ongoing Phase 2 registration-enabling cohort of the KRYSTAL-1 study in previously-treated patients with KRASG12C-mutated NSCLC for presentation at a medical congress in early 2022.

"The KRAS mutation has historically been challenging to target, leaving patients with limited treatment options," said Charles M. Baum, M.D., Ph.D., president and chief executive officer, Mirati Therapeutics, Inc. "These positive topline data further strengthen our belief in adagrasib as a potentially differentiated therapy for patients with non-small cell lung cancer harboring the KRASG12C mutation. We look forward to submitting our New Drug Application to the U.S. Food and Drug Administration in the fourth quarter of 2021 and advancing our expanding adagrasib development program, which includes numerous monotherapy and combination studies in KRASG12C-mutated solid tumors."

Updated Findings from Phase 1/1b NSCLC Cohort of KRYSTAL-1 Study

In addition to these topline Phase 2 results, the Company reported updated findings from the Phase 1/1b KRYSTAL-1 study evaluating adagrasib 600mg BID in all 19 patients enrolled with KRASG12C-mutated advanced NSCLC as of the June 15, 2021 data cutoff.

Results showed that the investigator assessed ORR was 58%. Two of the 11 responses occurred in patients after being on treatment for more than 10 months. The median follow-up was 17.3 months. The median duration of treatment and median duration of response were 9.5 months and 12.6 months, respectively. In addition, 64% of responders were still on treatment, and continuing to respond. The median progression free survival was 8.3 months and median overall survival was not reached. Grade 3/4 treatment related adverse events were observed in 26% of patients, with one Grade 5 event.

Virtual Investor Event

Mirati Therapeutics will host a virtual Investor Event on Monday, September 20, 2021 at 8:30 a.m. ET / 5:30 a.m. PT.

Company executives will discuss:

A top-line update from the Phase 2 registrational cohort of the KRYSTAL-1 study evaluating adagrasib in previously-treated patients with KRASG12C-mutated NSCLC
Findings from the colorectal cancer (CRC) cohort of the Phase 1/2 KRYSTAL-1 study evaluating adagrasib as monotherapy and in combination with cetuximab in patients with heavily pretreated CRC harboring the KRASG12C mutation, as presented at the 2021 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress
Results from the Phase 2 MRTX-500 study evaluating sitravatinib combined with nivolumab in patients with non-squamous NSCLC who progressed on or after prior checkpoint inhibitor therapy, to be presented at the 2021 ESMO (Free ESMO Whitepaper) Congress
Investors and the general public are invited to register and listen to a live webcast of the event through the "Investors and Media" section on Mirati.com. A replay of the event will be available shortly after the conclusion of the event.

About the KRYSTAL-1 Study

KRYSTAL-1 is an open-label Phase 1/2 multiple expansion cohort trial evaluating adagrasib as monotherapy and in combination with other anticancer therapies in patients with advanced solid tumors harboring the KRASG12C mutation.

About KRASG12C in Non-Small Cell Lung Cancer

Lung cancer is one of the most common cancers worldwide, accounting for 2.21 million new cases and 1.8 million deaths worldwide in 2020. Lung cancer consists of non-small cell lung cancer (NSCLC) in approximately 85 percent of cases and small cell lung cancer (SCLC) in approximately 15 percent of cases. KRASG12C is the most common KRAS mutation in NSCLC, present in approximately 14 percent of patients with lung adenocarcinoma, and is a biomarker mutation of poor prognosis.

About Adagrasib (MRTX849)

Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24-48 hours. Adagrasib is a being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.

On September 20, 2021 PharmAbcine Inc. (KOSDAQ: 208340ks), a clinical-stage biotech company focusing on the development of next generation antibody therapeutics, reported that the Company will virtually participate in the 27th annual BIO-Europe which will take place from October 25 – 28, 2021 (Press release, PharmAbcine, SEP 20, 2021, View Source [SID1234588053]).

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BIO-Europe is Europe’s largest annual partnering conference serving the global life science industry. It attracts a wide range of business leaders, including senior executives of leading biotech companies, business development teams from large and midsize pharmaceutical companies, investors and other industry experts. This year, more than 3,500 executives from over 1,000 life sciences companies around the world are expected to participate in the event.

During the event, PharmAbcine’s business development team will conduct one-to-one partnering meetings with biotech companies around the world to broaden its global network, explore mutual interests, and identify recent trends in drug development market. Also, the Company will present a pre-recorded video which will be made available on-demand. The video will feature Dr. Jin-San Yoo, CEO of PharmAbcine, who will introduce the Company’s core technology and give updates on the R&D progress of the main pipelines such as olinvacimab, PMC-403, and PMC-309.

Olinvacimab, an anti-VEGFR2 (Vascular Endothelial Growth Factor Receptor 2) fully human antibody, is the Company’s leading pipeline and is undergoing multiple global clinical trials. In early September 2021, PharmAbcine initiated a Phase II olinvacimab and pembrolizumab combo study for the treatment of mTNBC (metastatic Triple-Negative Breast Cancer) in Australia. Also, a Phase II olinvacimab mono study for bevacizumab-nonresponding rGBM (recurrent glioblastoma multiforme) patients at multiple sites in both US and Australia and two Phase Ib olinvacimab and pembrolizumab combo trials in mTNBC and rGBM in Australia are still ongoing.

PMC-403 is a novel TIE2-activating fully human antibody designed to stabilize and repair damaged blood vessels in a variety of diseases. PMC-403 is currently in development for treating AMD (Age-related Macular Degeneration), DME (Diabetic Macular Edema), and DR (Diabetic Retinopathy) which are common abnormal vascular-related eye diseases. The Company expects PMC-403 to enter global clinical trials for both ophthalmology and oncology in 2022.

PMC-309 is a novel anti-VISTA (V-domain Ig Suppressor of T cell Activation) antagonizing antibody in development for the treatment of various tumor types. VISTA plays a pivotal role in maintaining the immunosuppressive environment around the tumor cells and is expressed primarily on MDSC (Myeloid-Derived Suppressor Cells) and Tregs (regulatory T cells). Blocking VISTA pathways activates T cells’ immune responses and leads to better anti-tumor effects. PMC-309 is expected to enter a global clinical trial in 2022.

To request a partnering meeting with PharmAbcine, register for the event here.