On May 20, 2021 GammaDelta Therapeutics ("GammaDelta"), a company focussed on exploiting the unique properties of gamma delta (γδ) T cells for immunotherapy, reported the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for the Company’s allogeneic variable delta 1 (Vδ1) gamma-delta (γδ) T cell therapy, GDX012, to be investigated as a treatment for haematological malignancies (Press release, GammaDelta Therapeutics, MAY 20, 2021, View Source [SID1234580384]). The FDA also granted orphan drug designation to allogeneic Vδ1 γδ T cell therapy (GDX012) for the treatment of Acute Myeloid Leukaemia (AML).

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!

Dr. Paolo Paoletti, CEO of GammaDelta Therapeutics, commented: "The clearance of our IND application for GDX012 marks an important step for our company in establishing a portfolio of innovative allogeneic cell therapies. The unique properties of Vδ1 γδ T cells will be evaluated for the first time in a clinical study for patients with AML. This important milestone results from our efforts to establish a robust pipeline of cellular immunotherapies derived from our proprietary platforms and processes for the isolation and expansion of Vδ1 γδ T cells from both blood and tissues for targeting haematological malignancies and solid tumours."

GammaDelta plans to initiate a Phase 1 clinical trial for patients with measurable residual disease (MRD) positive AML. Expected to begin later in 2021 as a multicentre study in the US, the trial will evaluate safety, tolerability and anti-leukemic activity of GDX012. GammaDelta Therapeutics is advancing its novel T cell platform under an ongoing collaboration with Takeda Pharmaceutical Company Limited ("Takeda") formed in 2017.

Dr. Michael Koslowski, Head of R&D and Chief Medical Officer of GammaDelta Therapeutics, said: "Although progress has been made in the treatment of AML, the median overall five-year survival rate for patients diagnosed with AML remains under 30 percent. With the development of GDX012 we are aiming to change the treatment paradigm for AML and potentially other haematologic malignancies. The unique biological characteristics of Vδ1 γδ T cells offer a first-in-class Vδ1 γδ T cell therapy for AML, where the development of cell therapies has been historically limited due to the lack of specific targets."

Dr. Chris Arendt, Oncology Therapeutic Area Unit Head of Takeda, commented: "The progression of GammaDelta Therapeutics’ platform technology underscores the potential of γδ T cells and the power of the innate immune system. Through collaboration with pioneers like GammaDelta Therapeutics, we hope to advance next-generation cell therapies and to maximise off-the-shelf treatments in the battle against hard-to-treat cancers."

GammaDelta has developed proprietary technologies to generate both blood-and tissue-derived allogeneic immunotherapies based on Vδ1 γδ T cells for the treatment of haematologic malignancies and solid tumours. Both platforms have enabled the creation of highly active and selective non-engineered and genetically engineered allogeneic cell therapies, which demonstrate cellular activity and tumour cell killing capacity. Vδ1 γδ T cells are a unique subset of T cells that specifically recognise and are activated by molecular patterns of dysregulation on cancer cells. The non-MHC-restricted activity of Vδ1 γδ T cells makes them a unique cell type for the development of fully allogeneic, "off-the-shelf" cell therapies.

On May 20, 2021 The Janssen Pharmaceutical Companies of Johnson & Johnson reported updated data from the Phase 1 CHRYSALIS study showing treatment with amivantamab in combination with lazertinib led to a median duration of response (DOR) of 9.6 months in chemotherapy-naïve patients with non-small cell lung cancer (NSCLC) and EGFR exon 19 deletion or L858R mutations whose disease had progressed after treatment with osimertinib (Press release, Johnson & Johnson, MAY 20, 2021, View Source [SID1234580400]).1

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!

These data, which will be presented in an oral presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on Friday, June 4, also provide new insights on the importance of biomarkers to identify a subgroup of patients more likely to respond to amivantamab and lazertinib (Abstract #9006). Results from the CHRYSALIS study have led to new studies to further evaluate the potential of amivantamab and lazertinib combination therapy, which include the Phase 3 MARIPOSA study and Phase 1/1b CHRYSALIS-2 study.2,3

"Typically, patients whose disease no longer responds to osimertinib therapy would have little opportunity to seek additional treatments, other than chemotherapy. However, the durable responses we are seeing with the combination of amivantamab and lazertinib suggest an additional targeted option may be possible," said Byoung Chul Cho, M.D., Ph.D., Yonsei Cancer Center, Yonsei University College of Medicine in Seoul, South Korea, and lead study investigator.† "The results from this CHRYSALIS study cohort also offer promising insights that may help identify patients more likely to respond to an amivantamab and lazertinib combination regimen."

In the combination cohort of the Phase 1 CHRYSALIS study, 45 patients with NSCLC with EGFR exon 19 deletion or L858R mutations whose disease had progressed on osimertinib, but who had not yet received chemotherapy, received the combination dose of 1050 mg (for patients who weigh ˂80kg) or 1400 mg (for patients who weigh ≥80kg) amivantamab and 240 mg lazertinib.1 Of those patients, 36 percent (95 percent confidence interval [CI], 22-51) had a confirmed response (CR) (one complete response and 15 partial responses [PR]) with the regimen.1 The median DOR was 9.6 months (95 percent CI, 5.3- not reached).1 The median progression-free survival (mPFS) was 4.9 months (95 percent CI, 3.7–9.5) and the Clinical Benefit Rate (CBR) was 64 percent (95 percent CI, 49-78).1

In the study, each patient’s tumour was characterised through genetic testing of circulating tumour DNA and tumour tissue biopsy to identify the mechanism(s) of resistance to osimertinib. The study identified 17 patients with EGFR and/or MET-based resistance; of those patients, the overall response rate was 47 percent, median DOR was 10.4 months, CBR was 82 percent, and median progression-free survival was 6.7 months.1 Of the remaining 28 patients without identified EGFR or MET-based resistance, 29 percent of patients experienced a confirmed tumour response.1 Among these 28 patients, 18 had unknown mechanisms of osimertinib-resistance and 10 had non-EGFR/MET mechanisms of resistance.1 The study also examined 20 patients who had sufficient tumour tissue to do immunohistochemistry (IHC) staining for EGFR and MET expression. Among 10 patients whose tumours stained high for EGFR and MET expression, 90 percent had a tumour response.1 Janssen will prospectively validate both next-generation sequencing (NGS) and IHC based biomarkers to identify patients most likely to benefit from amivantamab and lazertinib in a cohort in the CHRYSALIS-2 study.

The most common adverse events (AEs) were predominantly Grade 1-2 and included infusion-related reactions (78 percent), rash (acneiform dermatitis, 51 percent + rash, 27 percent) and paronychia (49 percent).1 16 percent of patients experienced treatment-related Grade ≥3 AEs. Discontinuations were seen in four percent and dose reductions in 18 percent of patients.1

In the post-platinum, EGFR exon 20 insertion mutation NSCLC setting, Janssen will present an indirect treatment comparison demonstrating that clinical trial patients treated with amivantamab monotherapy had a 10-month higher overall survival (OS) compared to those treated with real-world therapies such as immune checkpoint inhibitors, tyrosine kinase inhibitors (TKIs) and single-agent chemotherapies (Abstract #9052) in U.S. databases.4 In a separate study using French real-world data from the Epidemiological Strategy and Medical Economics (ESME) database, the prognosis for patients with NSCLC with EGFR exon 20 insertion mutations appears to be worse compared to those with the common EGFR mutations, exon 19 deletions and L858R (Abstract #9062).5

"Patients with non-small cell lung cancer and EGFR mutations continue to experience significant unmet need for treatment options and often face a poor prognosis," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumours, Janssen Research & Development, LLC. "We remain committed in our efforts to transform the treatment of lung cancer through the ongoing investigation of amivantamab as a monotherapy and in combination with lazertinib as a potential treatment option for patients with various genetic alterations."

"Janssen is committed to researching and developing new precision treatments for patients facing limited effective treatment options, such as non-small cell lung cancer with EGFR mutations, which often results in a poor prognosis for patients with this disease," said Dr Catherine Taylor, Vice President, Medical Affairs for Europe, Middle East and Africa, Therapeutic Area Strategy, Johnson & Johnson Middle East FZ-LLC. "By bringing together our heritage in oncology and our challenger mindset, we aim to break new ground and make a meaningful impact in this area of great unmet need in lung cancer."

About the CHRYSALIS Study
CHRYSALIS (NCT02609776) is an open-label, multicentre, first-in-human Phase 1 study to evaluate the safety, pharmacokinetics and preliminary efficacy of amivantamab as a monotherapy and in combinations, including with lazertinib, in patients with advanced NSCLC with various EGFR mutations.6 The study will enroll 460 patients with advanced NSCLC.6 The study consists of two parts: the first consists of amivantamab monotherapy and combination dose escalations, and the second consists of amivantamab monotherapy and combination dose expansions.6

The results from the CHRYSALIS study have led to new studies to further evaluate the potential of amivantamab and lazertinib combination therapy. The Phase 3 MARIPOSA study (NCT04487080) will assess the amivantamab and lazertinib combination against osimertinib in untreated advanced EGFR-mutated NSCLC,2 and a Phase 1/1b study, CHRYSALIS-2, (NCT04077463) has been initiated to examine the combination in patients who have progressed after treatment with osimertinib and chemotherapy.3

About Amivantamab
Amivantamab is an investigational, fully-human EGFR-MET bispecific antibody with immune cell-directing activity that targets tumours with activating and resistance EGFR mutations and MET mutations and amplifications.7,8,9,10 Amivantamab is being studied as a monotherapy in patients with EGFR exon 20 insertion mutations.6 Amivantamab is also being studied in combination with lazertinib in adult patients with advanced NSCLC.6 Janssen has filed regulatory submissions in the U.S. and Europe seeking approval of amivantamab for the treatment of patients with metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.11,12 These applications mark the first-ever regulatory submissions for a treatment for patients with NSCLC with EGFR exon 20 insertion mutations.13 Amivantamab is being studied in multiple clinical trials, including as first-line therapy in untreated advanced EGFR-mutated NSCLC in the Phase 3 MARIPOSA (NCT04487080) study assessing amivantamab in combination with lazertinib, the Phase 3 PAPILLON (NCT04538664) study assessing amivantamab in combination with carboplatin-pemetrexed for patients with advanced or metastatic EGFR-mutated NSCLC and exon 20 insertion mutations, and the Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous (SC) administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab SC delivery.2,14,15

About Lazertinib
Lazertinib is an oral, third-generation, brain-penetrant, EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR.16 Interim safety and efficacy results from the lazertinib Phase 1-2 study were published in The Lancet Oncology in 2019.16 In 2018, Janssen Biotech, Inc. entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.17

About Non-Small Cell Lung Cancer (NSCLC)
In Europe, it is estimated that 477,534 patients were diagnosed with lung cancer in 2020, with around 85 percent diagnosed with NSCLC.18,19 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.20 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.21 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase supporting cell growth and division.22 EGFR mutations are present in 10 to 15 percent of Caucasian patients with NSCLC and occur in 40 to 50 percent of Asian patients who have NSCLC adenocarcinoma.23 The five-year survival rate for all people with metastatic NSCLC and EGFR mutations who are treated with EGFR TKIs is less than 20 percent.24,25

About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at www.janssen.com/emea. Follow us at www.twitter.com/janssenEMEA for our latest news. Janssen Research & Development, LLC, Janssen Pharmaceutica NV and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

On May 20, 2021 Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) reported that the BioNTech Europe GmbH has entered into an agreement with Turkey’s Ministry of Health to supply 60 million additional doses of the companies’ COVID-19 vaccine, with an option for an additional 30 million doses. On December 25, 2020, the two companies announced an initial agreement to provide 30 million doses of the Pfizer-BioNTech vaccine to Turkey (Press release, BioNTech, MAY 20, 2021, View Source [SID1234580352]). This second supply agreement brings the total number of doses to be supplied to Turkey to up to 120 million, all of which will be delivered in 2021.

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!

"Our goal is to deliver as many doses of our COVID-19 vaccine as possible to people around the world to help end this pandemic, reduce COVID-19-related hospitalisations and return to a normal life. We are grateful to be able to make an important contribution to Turkey’s vaccination efforts and for the trust placed in us," said Ugur Sahin, M.D., CEO and Co-founder of BioNTech.

"We are hopeful that this agreement will further boost Turkey’s COVID-19 vaccination drive. Pfizer is committed to contributing to public health in Turkey and very proud to have a global partner such as BioNTech in the global fight against the pandemic," said M. Cem Açık, Pfizer Country Manager Turkey.

The vaccine, which is based on BioNTech’s proprietary mRNA technology, was developed by both BioNTech and Pfizer. BioNTech is the Marketing Authorization Holder in the European Union, and the holder of emergency use authorizations or equivalent in the United States (jointly with Pfizer), United Kingdom, Canada and other countries in advance of a planned application for full marketing authorizations in these countries.

AUTHORIZED USE IN THE U.S.:
The Pfizer-BioNTech COVID-19 vaccine is authorized for use under an Emergency Use Authorization (EUA) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older.

IMPORTANT SAFETY INFORMATION FROM U.S. FDA EMERGENCY USE AUTHORIZATION PRESCRIBING INFORMATION:

Do not administer Pfizer-BioNTech COVID-19 vaccine to individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the Pfizer-BioNTech COVID-19 vaccine
Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of Pfizer-BioNTech COVID-19 vaccine
Monitor Pfizer-BioNTech COVID-19 vaccine recipients for the occurrence of immediate adverse reactions according to the Centers for Disease Control and Prevention guidelines (View Source)
Syncope (fainting) may occur in association with administration of injectable vaccines, in particular in adolescents. Procedures should be in place to avoid injury from fainting
Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the Pfizer-BioNTech COVID-19 vaccine
The Pfizer-BioNTech COVID-19 vaccine may not protect all vaccine recipients
In clinical studies, adverse reactions in participants 16 years of age and older included pain at the injection site (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), fever (14.2%), injection site swelling (10.5%), injection site redness (9.5%), nausea (1.1%), malaise (0.5%), and lymphadenopathy (0.3%)
In a clinical study, adverse reactions in adolescents 12 through 15 years of age included pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), injection site redness (8.6%), lymphadenopathy (0.8%), and nausea (0.4%)
Severe allergic reactions, including anaphylaxis, and other hypersensitivity reactions, diarrhea, vomiting, and pain in extremity (arm) have been reported following administration of the Pfizer-BioNTech COVID-19 vaccine outside of clinical trials. Additional adverse reactions, some of which may be serious, may become apparent with more widespread use of the Pfizer-BioNTech COVID-19 vaccine
Available data on Pfizer-BioNTech COVID-19 vaccine administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy
Data are not available to assess the effects of Pfizer-BioNTech COVID-19 vaccine on the breastfed infant or on milk production/excretion
There are no data available on the interchangeability of the Pfizer-BioNTech COVID-19 vaccine with other COVID-19 vaccines to complete the vaccination series. Individuals who have received one dose of Pfizer-BioNTech COVID-19 vaccine should receive a second dose of Pfizer-BioNTech COVID-19 vaccine to complete the vaccination series
Vaccination providers must report Adverse Events in accordance with the Fact Sheet to VAERS online at View Source For further assistance with reporting to VAERS call 1-800-822-7967. The reports should include the words "Pfizer-BioNTech COVID-19 Vaccine EUA" in the description section of the report
Vaccination providers should review the Fact Sheet for Information to Provide to Vaccine Recipients/Caregivers and Mandatory Requirements for Pfizer-BioNTech COVID-19 vaccine Administration Under Emergency Use Authorization
Please see Emergency Use Authorization (EUA) Fact Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers) including Full EUA Prescribing Information available at www.cvdvaccine-us.com.

On May 20, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported clinical and biomarker data demonstrating clinical proof-of-concept for pelareorep-checkpoint inhibitor combination therapy in pancreatic cancer (Press release, Oncolytics Biotech, MAY 20, 2021, View Source [SID1234580368]). The data will be featured in an upcoming electronic poster presentation at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is taking place virtually from June 4 – 8, 2021.

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 newly announced data are from a phase 2 trial evaluating pelareorep in combination with the PD-1 inhibitor pembrolizumab (KEYTRUDA) in pancreatic adenocarcinoma patients who progressed after first-line treatment. Findings from the trial indicate that pelareorep and pembrolizumab synergize and show anti-cancer activity in these difficult-to-treat patients, which is mediated through the complementary immunotherapeutic effects of the two agents.

"These results are very promising, particularly considering the extremely challenging patient population enrolled in the trial. That we saw a response signal in select patients, despite the absence of chemotherapy, provides evidence of the considerable anti-cancer activity of pelareorep-pembrolizumab combination therapy," said Principal Investigator, Devalingam Mahalingam, M.D., Ph.D., Associate Professor of Medicine at The Northwestern University Feinberg School of Medicine and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. "We notably observed an association between treatment-induced anti-cancer immune responses and improved tumor control in some patients, which demonstrates pelareorep’s underlying immunologic mechanism of action and validates the strategy of combining it with checkpoint inhibition. I look forward to discussing these data with the scientific community at the upcoming ASCO (Free ASCO Whitepaper) conference and to the continued evaluation of pelareorep-checkpoint inhibitor combination therapy in select patients with pancreatic and other gastrointestinal cancers."

The data presented in the upcoming ASCO (Free ASCO Whitepaper) poster represent an update based on additional data that was collected after the cutoff date used for the poster’s corresponding abstract. Key data and conclusions that will be featured in this upcoming poster include:

Disease control was achieved in 42% (5/12) of patients, with one patient achieving a partial response and four patients achieving stable disease
On-treatment tumor biopsies showed pelareorep replication and increased infiltration of CD8+ T cells and PD-L1+ cells relative to pre-treatment samples
Patients achieving disease control showed reductions in pro-tumor regulatory T (T­reg) cells in the peripheral blood and tumor tissue compared to those with progressive disease
Patients achieving disease control showed increased activation of anti-cancer CD8+ T cells in the peripheral blood compared to those with progressive disease
Pelareorep-pembrolizumab combination therapy was found to be well tolerated, with most treatment-related adverse events being grade 1 or 2
Bin Zhang, M.D., Ph.D., Professor at The Northwestern University Feinberg School of Medicine, commented, "These data show that pelareorep can train the immune system to target pancreatic cancer while simultaneously promoting the infiltration of T cells into the tumor and remodeling the tumor microenvironments (TMEs) to be less immunosuppressive. This positions pelareorep to synergistically combine with both checkpoint inhibitors as well as a broad range of other immuno-oncology agents."

"The findings from this study highlight the broad applicability of pelareorep’s immunotherapeutic mechanism of action as they are consistent with what has been seen in clinical trials in other indications such as breast cancer," added Thomas Heineman, M.D., Ph.D., Global Head of Clinical Development and Operations at Oncolytics. "The compelling findings from this phase 2 study highlight the potential of pelareorep to address the critical unmet need in pancreatic cancer by reversing the immunosuppressive TMEs that often limit the efficacy of checkpoint inhibitors. The anti-cancer activity demonstrated in this study bodes well for a successful outcome in our GOBLET trial, which includes a cohort evaluating pelareorep and the PD-L1 inhibitor atezolizumab in combination with chemotherapy as first-line therapy in metastatic pancreatic cancer patients."

The electronic poster, titled, "Treatment with pembrolizumab in combination with the oncolytic virus pelareorep promotes anti-tumor immunity in patients with advanced pancreatic adenocarcinoma" will be made available on the ASCO (Free ASCO Whitepaper) Annual Meeting website at 9:00 a.m. ET on June 4, 2021. A copy of the poster will also be posted on the Posters & Publications page of Oncolytics’ website (LINK).

Oncolytics plans to further develop pelareorep-checkpoint inhibitor combination therapy in pancreatic cancer in collaboration with Roche and AIO-Studien-gGmbH (AIO) through the GOBLET study, a phase 1/2 multi-center trial designed to investigate the use of pelareorep in combination with Roche’s anti-PD-L1 inhibitor atezolizumab (Tecentriq) in patients with metastatic pancreatic, metastatic colorectal and advanced anal cancers (link to the GOBLET announcement PR). Oncolytics expects the first patient to be dosed in GOBLET in mid-2021.

About GOBLET

The GOBLET (Gastrointestinal tumOrs exploring the treatment comBinations with the oncolytic reovirus peLarEorep and anTi-PD-L1) study is a phase 1/2 multiple indication biomarker, safety, and efficacy study in advanced or metastatic GI tumors. The study will be conducted at 25 centers in Germany. The primary endpoint of the study is safety, with overall response rate and biomarker evaluation (T cell clonality and CEACAM6) as exploratory endpoints. Approximately 55 patients are planned for enrollment across four separate cohorts:

Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1st line metastatic pancreatic cancer patients (n=12);
Pelareorep in combination with atezolizumab in 2nd and 3rd line metastatic colorectal cancer patients that are diagnosed as MSI (microsatellite instability) high (n=19);
Pelareorep in combination with atezolizumab and TAS-102 in 3rd line metastatic colorectal cancer patients (n=14); and
Pelareorep in combination with atezolizumab in 2nd line advanced and unresectable anal cancer patients (n=10).
About Gastrointestinal Cancer

Excluding skin cancers, colorectal cancer is the third most common cancer, with an estimated 104,610 new cases of colon cancer and 43,340 new cases of rectal cancer diagnosed in the U.S. in 20201. Also, for the 2020 year, the American Cancer Society estimates there will be 57,600 new cases of pancreatic cancer2 and 8,590 new cases of anal cancer 3 in the U.S.

On May 20, 2021 Xilio Therapeutics, a biotechnology company developing tumor-selective immuno-oncology therapies for patients with cancer, reported the presentation of data from preclinical studies of XTX202, its tumor-selective interleukin-2 (IL-2) product candidate, demonstrating selective anti-tumor activity and favorable tolerability with no systemic toxicity observed (Press release, Xilio Therapeutics, MAY 20, 2021, View Source [SID1234580385]). The data will be reported in a poster entitled "XTX202, a protein-engineered IL-2, exhibits tumor-selective activity in mice without peripheral toxicities in non-human primates" at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The poster will be made available on the ASCO (Free ASCO Whitepaper) Annual Meeting website at the start of the meeting on June 4, 2021 at 9am ET.

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!

Xilio is leveraging its proprietary platform to engineer novel molecules that are designed to be activated in the tumor microenvironment (TME) and have the potential to result in localized, tumor-selective clinical activity without dose-limiting toxicities. XTX202, Xilio’s lead cytokine product candidate, is an engineered form of IL-2 that is masked with a protein domain to prevent binding activity until cleaved off by TME-associated proteases.

"The power of IL-2 to activate the immune system as a cancer therapeutic is promising, but utility of IL-2 agents has historically been greatly reduced due to toxicities," said Rónán O’Hagan, Ph.D., chief scientific officer of Xilio. "We have engineered XTX202 to overcome those challenges, with key features designed to ensure it is released and activated locally within the TME, where it selectively binds to IL-2 receptors on immune cells. We are excited to present these data which, for the first time, demonstrate selective tumor-inhibition and favorable tolerability of XTX202 in preclinical models. With these data, we plan to complete IND-enabling studies and submit an IND application in the second half of 2021 to evaluate XTX202 in patients with solid tumors."

Data reported in the poster are from preclinical studies in both mouse and non-human primate (NHP) models, including comparisons between XTX202 and XTX200, a non-masked, parent version of XTX202, as well as aldesleukin, a synthetic form of IL-2 approved for certain cancer indications by the U.S. Food and Drug Administration. Key data include:

XTX202, in its masked form, did not bind to IL-2 receptors, and matrix metalloproteinase (MMP) activation of XTX202 restored full binding to IL-2 receptor beta that is found on immune activating CD8 T cells and natural killer cells, illustrating the tight, protease-dependent control of IL-2 activity conferred by XTX202.
XTX202 was engineered to eliminate binding to IL-2Ra in order to enhance immune activation by CD8 T cells and NK cells, and to minimize immune suppression by regulatory T cells. No binding to IL-2Ra was detectable even after MMP-dependent activation of XTX202.
XTX202 inhibited tumor growth in syngeneic mouse models as a single agent with no evidence of toxicity or peripheral immune activation, thus demonstrating tumor selective activity.
XTX202 matched the tumor growth inhibition activity of aldesleukin and the non-masked control XTX200, without activation of immune response outside the TME, thereby avoiding the body weight loss in mice that was associated with doses of XTX200 or aldesleukin required for tumor growth inhibition.
XTX202 was well-tolerated in repeat dose studies in NHPs at doses up to 30 mg/kg.
XTX202 is estimated to have a greater than 100-fold improvement in therapeutic index compared to aldesleukin.