1stOncology™: Cancer Intelligence Service – Page 8206 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Novartis top-line results for CANOPY-1 Phase III study support further evaluation of canakinumab in lung cancer

On October 25, 2021 Novartis reported that the CANOPY-1 Phase III study did not demonstrate the statistically significant primary endpoints of overall survival (OS) and progression-free survival (PFS) in patients treated with canakinumab (ACZ885) combined with pembrolizumab plus platinum-based doublet chemotherapy, compared to patients receiving placebo in combination with pembrolizumab plus platinum-based doublet chemotherapy1 (Press release, Novartis, OCT 25, 2021, View Source [SID1234591880]). The trial data, however, showed potentially clinically meaningful improvements in both PFS and OS in pre-specified subgroups of patients based on the baseline inflammatory biomarker, hs-CRP, as well as other biomarker-defined subgroups. These data support further evaluation of canakunimab in lung cancer.

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!

"CANOPY-1 provides critical insights into the treatment of this devastating disease, and we will continue to analyze the data and conclusions, as well as their potential clinical implications," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "While this trial did not confirm the benefit for all patients we hoped for, we are energized by the overall CANOPY-1 findings as they support our commitment to continue studying canakinumab in lung cancer. We share our gratitude and thanks to the CANOPY-1 study patients and clinical investigators for their partnership."

Novartis and investigators are collaborating on further data analysis and will present the full dataset at an upcoming medical meeting. The company is continuing with the evaluation of canakinumab in lung cancer, and is applying findings to the overall lung cancer development plan.

The comprehensive CANOPY clinical trial program continues with CANOPY-A, a Phase III study investigating canakinumab as an adjuvant therapy (after surgery)2, and CANOPY-N, a Phase II study in the neoadjuvant setting (before surgery)5. Enrollment for both trials is ongoing2,5. Patients in the CANOPY-A trial more closely reflect the earlier CANTOS study population than those in the CANOPY-1 trial2,3,4. CANTOS was the first study to show that blocking the IL-1β inflammatory signal may potentially reduce lung cancer’s incidence and mortality3.

Canakinumab is a potential first-in-class interleukin-1beta (IL-1β) inhibitor of the Pro-Tumor Inflammation (PTI) pathway in NSCLC6. PTI, which enables tumor development by driving cancer-causing processes and suppressing anti-tumor immune responses, is one of the potential hallmarks of cancer and targets in NSCLC3,6. Novartis is developing other potential PTI pathway inhibitors, which are at various stages of development, including gevokizumab7,8.

About canakinumab (ACZ885)
Canakinumab is a human monoclonal antibody that binds with high affinity and selectivity to human interleukin-1beta (IL-1β) and neutralizes IL-1β activity by blocking its interaction with its receptors9,10. By neutralizing IL-1β, preliminary evidence suggests that canakinumab may inhibit Pro-Tumor Inflammation (PTI) to 1) enhance anti-tumor immune response; 2) reduce tumor cell proliferation, survival, and invasiveness; and 3) impair angiogenesis11. PTI enables tumor development by driving cancer-causing processes and suppressing anti-tumor immune responses3,6. Canakinumab is a potential first-in-class IL-1β inhibitor of the PTI pathway in NSCLC6.

About the CANOPY program
Novartis launched the CANOPY study program after observing significantly lower than expected rates of lung cancer mortality among patients in the Phase III cardiovascular CANTOS trial. The CANTOS trial evaluated canakinumab as a secondary prevention measure for cardiovascular events in patients following a heart attack3,11. Patients in the CANTOS trial also were at high risk for inflammatory cancers, like lung cancer, due to advanced age, smoking history, and other clinical risk factors3,11. Based on these findings, Novartis launched three large-scale, randomized, Phase III clinical trials and a Phase II clinical trial to investigate canakinumab as a potential treatment option in non-small cell lung cancer (NSCLC).

CANOPY-A (NCT03447769) is a double-blind, placebo-controlled Phase III trial studying canakinumab in the adjuvant setting following surgical resection and cisplatin-based chemotherapy, if required2. The adjuvant study is designed to determine if treatment with canakinumab can prevent cancer relapse2.
CANOPY-N (NCT03968419) is a Phase II neoadjuvant trial evaluating canakinumab either as monotherapy or in combination with pembrolizumab among patients with resectable NSCLC prior to their planned surgery5.
CANOPY-1 (NCT03631199) was a double-blind, placebo-controlled Phase III trial evaluating canakinumab as a first-line treatment for locally advanced or metastatic NSCLC in combination with pembrolizumab and platinum-based doublet chemotherapy4. As reported today, the trial did not met its primary endpoints of overall survival (OS) and progression-free survival (PFS)1.
CANOPY-2 (NCT03626545) was a double-blind, placebo-controlled Phase III trial investigating the role of canakinumab in combination with the chemotherapy agent docetaxel in second- or third-line therapy versus docetaxel alone in NSCLC12. In March 2021, Novartis announced that the trial did not meet its primary endpoint, and data were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2021 Congress13.
Novartis and lung cancer
Lung cancer is one of the most common cancers worldwide, accounting for more than 2 million new cases diagnosed each year14. More people die of lung cancer every year than any other cancer14. There are two main types of lung cancer—small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)15. NSCLC accounts for approximately 85% of lung cancer diagnoses14,16.

Novartis is committed to working with the scientific and medical communities to reimagine the treatment of lung cancer and pursue advances in medicine that could extend the survival of people living with lung cancer. With one of the most diverse lung cancer development programs in the industry, Novartis is: developing experimental therapies that block cancer growth; learning more about ways to activate the body’s immune system; increasing understanding of the relationship between chronic inflammation and tumor growth and progression; and exploring the potential for advanced nuclear medicine to fight the disease. As part of this continuing and broad commitment to targeting lung cancer, data from CANOPY-1 will be evaluated and used to inform canakinumab’s future development program, including potential combination studies with tislelizumab.

Cedilla Therapeutics Completes $82.6

On October 25, 2021 Cedilla Therapeutics, a biotechnology company bringing a new dimension to precision oncology, reported that it has raised an additional $25 million in an expansion of its Series B financing, bringing the total amount raised to $82.6 million (Press release, Cedilla Therapeutics, OCT 25, 2021, View Source [SID1234591879]). The oversubscribed Series B expansion includes new investors RA Capital Management, Janus Henderson Investors, Woodline Partners LP and Logos Capital, along with participation from existing investor Third Rock Ventures.

"We are grateful for the support from our new and existing investors, which reflects the promise of our novel approach to conditionally modulating proteins as well as the unique potential of our lead programs, inhibitors against TEAD and CDK2, two critical but historically undruggable targets," said Alexandra Glucksmann, Ph.D., President and Chief Executive Officer of Cedilla Therapeutics. "With this financing, we plan to accelerate and expand our development efforts by progressing our most advanced programs toward the clinic while continuing to invest in ongoing discovery efforts against additional high value cancer targets."

Proceeds from the financing will support Cedilla’s continued growth and development of its two lead programs, an inhibitor of TEAD for the treatment of solid tumors, such as mesothelioma and certain squamous cell carcinomas, and a highly selective inhibitor of CDK2/Cyclin E for the treatment of multiple tumor types, including CDK4/6-resistant breast cancer, ovarian, uterine, stomach and esophageal cancers. The company plans to initiate investigational new drug application-enabling studies for the TEAD program in the first half of 2022 and for the CDK2 program in the second half of 2022.

In conjunction with the financing, Jake Simson, Ph.D., Partner at RA Capital Management, joins Cedilla’s Board of Directors.

Dr. Glucksmann continued, "We are pleased to welcome Jake to our Board of Directors. He brings a wealth of experience advising companies from the earliest stages of company formation through their maturation into fully integrated biopharmaceutical organizations. We look forward to his many contributions as we continue to grow Cedilla into a clinical-stage organization with a robust and growing portfolio of product candidates."

"Cedilla brings a new dimension to precision oncology by conditionally modulating proteins in their functional state," said Jake Simson, Ph.D., Partner at RA Capital Management. "Preclinical data generated to-date suggest that Cedilla’s lead programs may challenge historical perceptions of TEAD and CDK2 as undruggable targets and could offer patients new options that would be well-tolerated and extremely effective. In addition, Cedilla’s approach, based on a deep understanding of how the cellular context modulates protein activity, could deliver superior inhibitors against a range of other key cancer drivers. I look forward to partnering with the team with the aim to deliver a broad portfolio of small molecule medicines, each with potential profound benefit to patients."

Roche launches comprehensive genomic profiling kit to expand access to personalised cancer research

On October 25, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it has launched the AVENIO Tumor Tissue CGP Kit (Press release, Hoffmann-La Roche, OCT 25, 2021, View Source [SID1234591878]). The Kit complements the current CGP portfolio offered by Roche and Foundation Medicine and allows laboratories to expand their oncology research in-house. Ultimately, a future version of the kit may lead to additional resources for clinicians to use in the diagnosis and treatment of cancer.

Cancer is a disease of the genome and treatment no longer depends solely on the tissue of origin. Rather, cancer is a collection of dozens or even hundreds of diseases driven in part by specific genomic characteristics.

"To treat cancer effectively, we must understand what drives it at a molecular level. CGP helps inform decisions about available treatment options, including targeted therapies, immunotherapies, tumour-agnostic treatments and clinical trial participation, based on the unique genomic profile of a patient’s tumour," said Thomas Schinecker, CEO of Roche Diagnostics. "We are bringing powerful insights from CGP to enable smarter, more efficient research and development. Our new kit provides the information researchers need and will ultimately provide insights physicians can use to develop personalised treatment strategies for individual patients."

Unlike smaller panels such as hotspot or single gene tests, CGP tests deliver comprehensive information in a single test and can also provide information on complex genomic signatures such as Tumour Mutational Burden (TMB), Microsatellite Instability (MSI) and Loss of Heterozygosity (LOH).

The kit for research use is just the first step in bringing CGP closer to people living with cancer through enabling critical research and clinical trials in laboratories across the world. The kit will launch in regions throughout the world including Europe, North America, Asia and South America. Roche and Foundation Medicine also plan to develop additional solutions for its portfolio.

"The launch of this kit will significantly expand access to genomic profiling globally by providing an in-house solution for those who cannot otherwise access our portfolio of tests through our centralised laboratories," said Foundation Medicine Chief Executive Officer Brian Alexander. "The launch of the kit strengthens our ability to act as an essential partner to researchers in navigating the complex landscape of cancer care."

About the AVENIO Tumor Tissue CGP Kit
The AVENIO Tumor Tissue CGP Kit is a Research Use Only next-generation sequencing test that provides an end-to-end workflow from DNA extraction and library preparation to generation of variant results by the FoundationOne Analysis Platform via AVENIO Connect. The Kit uses a gene panel based on the FoundationOne platform that was designed to match the FoundationOne CDx panel content to analyse 324 cancer-related genes across four main classes of genomic alterations and genomic signatures known to cause and drive cancer. These genes provide valuable insights on biomarkers known today and emerging biomarkers of tomorrow.

Each of the kits is configured for running 24 samples, with the entire workflow from DNA isolation to variant results completed in 5 days. The kit runs on Illumina’s NextSeq 500/550 RUO and NextSeq 550 Dx System in research mode. In January 2020, Roche entered into an agreement with Illumina to develop, manufacture and commercialise AVENIO tests for both tissue and blood for use on Illumina’s IVD systems.

Evaxion Biotech Announces Clinical Collaboration to Evaluate Lead Product Candidate with KEYTRUDA® (pembrolizumab) in Patients with Melanoma

On October 25, 2021 Evaxion Biotech A/S (NASDAQ: EVAX), a clinical-stage biotechnology company specializing in the development of AI-driven immunotherapies to improve the lives of patients with cancer and infectious diseases, reported that it has entered into a clinical trial collaboration and supply agreement with subsidiaries of Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the United States and Canada), to evaluate the combination of Evaxion’s cancer immunotherapy EVX-01 with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in a new Phase 2b study (Press release, Evaxion Biotech, OCT 25, 2021, View Source [SID1234591877]).

The planned multicenter Phase 2b trial will enroll patients with metastatic melanoma stage III and stage IV and will investigate the personalized neoepitope immunotherapy EVX-01 in combination with KEYTRUDA. It is expected to be initiated in Q4 2021. Under terms of the agreement, Evaxion will be responsible for the conduct of the study; MSD will supply all of the necessary KEYTRUDA and will continue to collaborate as the data mature.

Lars Wegner, CEO of Evaxion, said: "We are extremely proud to collaborate with MSD, one of the world’s premier immuno-oncology companies, on our upcoming Phase 2b trial with EVX-01. The promising Phase 1/2a data, which we reported in July, showed that EVX-01 may be able to improve the treatment landscape in melanoma and potentially other cancers. Now that checkpoint inhibitors including KEYTRUDA have become the standard of care for these patients, we are excited about the potential additive benefits of our drug candidate to further improve treatment and to strengthen the evidence supporting our platform and clinical pipeline. Futhermore, this collaboration will also reduce the cost of conducting our Phase 2b trial on EVX-01."

The ongoing Phase 1/2a trial is investigating EVX-01, a novel personalized cancer neoepitope immunotherapy based on Evaxion’s proprietary PIONEER AI technology, for the treatment of patients with melanoma.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Kenilworth, NJ, USA.

ERYTECH Announces Results from TRYbeCA-1 Phase 3 Trial of Eryaspase in Patients with Second-line Advanced Pancreatic Cancer

On October 25, 2021 ERYTECH Pharma (Nasdaq & Euronext: ERYP), a clinical-stage biopharmaceutical company developing innovative therapies by encapsulating therapeutic drug substances inside red blood cells, reported top-line results from its Phase 3 TRYbeCA-1 clinical trial evaluating eryaspase as second-line treatment in 512 patients with metastatic pancreatic cancer (Press release, ERYtech Pharma, OCT 25, 2021, View Source [SID1234591875]). The trial did not meet its primary endpoint of overall survival (OS).

In the TRYbeCA-1 trial, eryaspase demonstrated an improvement in the primary endpoint of OS compared to chemotherapy alone with a hazard ratio (HR) of 0.92 (95% confidence interval (CI), 0.76-1.11) in the intent-to-treat population, and the difference was not statistically significant (p-value 0.375). The median OS for patients treated with eryaspase plus chemotherapy was 7.5 months (95% CI, 6.5-8.3), compared to 6.7 months (95% CI, 5.4-7.5) for chemotherapy alone.

Interestingly, while the patients treated with gemcitabine plus nabpaclitaxel did not experience a survival benefit from the addition of eryaspase, patients treated with eryaspase and an irinotecan-based chemotherapy regimen showed nominal survival benefit with a HR of 0.77 (95% CI, 5.7-1.05) over those treated with chemotherapy alone. This prespecified subgroup had a median OS of 8.0 months in the eryaspase-treated arm versus 5.7 months in the control arm (per protocol population).

Key secondary endpoints of the trial, including progression-free survival, disease control rate and objective response rate, showed benefit in favor of eryaspase.

The safety profile of eryaspase observed in the TRYbeCA-1 trial was consistent with earlier observations and previous safety reviews by the trial’s independent data monitoring committee (IDMC).

Further analysis of the data will be performed, and full results will be presented at an upcoming medical conference.

ERYTECH will now focus on its late-stage program in acute lymphoblastic leukemia (ALL) and pursue a path to approval in hypersensitive ALL based on positive results of NOPHO-sponsored Phase 2 trial. The Company reiterates its intention to submit a BLA before the end of the year.

"While the results are disappointing, we congratulate the company for a very well managed trial in this difficult disease. With a median survival of 7.5 months, ERYTECH has created a new reference standard for clinical evaluation in second line pancreatic cancer", said Prof. Pascal Hammel, MD, PhD, gastroenterologist-oncologist at Beaujon Hospital in Paris and co-principal investigator of the TRYbeCA-1 trial.

"I agree with Prof Hammel, and want to add that the results in the subgroup of fluoropyrimidine-based treatments are, with a median survival of 8 months, really remarkable and merit further investigation. Especially since this was also the better subgroup in the Phase 2b trial", said Prof. Manuel Hidalgo, M.D., Ph.D., Weill Cornell Medicine/NewYork-Presbyterian Hospital, and co-principal investigator of the study.

"Pancreatic cancer is a very challenging, heterogeneous disease, and the results of the TRYbeCA-1 Phase 3 trial have now also encountered this significant hurdle." said Dr Iman El Hariry, Chief Medical Officer of ERYTECH. "It is very disappointing that the clinical benefit eryaspase demonstrated in the Phase 2 trial was not confirmed; however, the study has addressed important questions in the management of pancreatic cancer patients. I want to thank the patients, their families and healthcare providers, our vendors, as well as our colleagues at ERYTECH, who overcame many obstacles, including the COVID-19 pandemic, to execute this important trial. Targeting the altered asparagine and glutamine metabolism of cancer cells, well established in ALL, remains an important field of development, also for the field of solid tumors. The ERYTECH team along with its clinical advisors will review the full data analyses including the secondary and exploratory endpoints and provide a more detailed update on additional subgroup analysis after these are completed".

"These results are highly disappointing, not only for the ERYTECH team, but also for patients and healthcare providers as there continues to be a major unmet medical need in pancreatic cancer." added Gil Beyen, CEO of ERYTECH. "We continue to believe in the potential of cancer metabolism and our ERYCAPS platform to treat aggressive forms of cancer, and will, while evaluating the potential to continue the development in pancreatic cancer, now continue to focus on seeking approval of eryaspase for ALL patients who developed hypersensitivity to pegylated asparaginase. This is also an important medical need and a potentially attractive market opportunity for eryaspase. We confirm our previously announced intention to submit a BLA for this indication by year-end 2021. We will evaluate our strategic and partnering options in the coming weeks and will provide updated guidance on our global corporate strategy later in the year."

TRYbeCA-1 Top-line Results and Analysis Conference Call Details

ERYTECH management will hold a conference call and webcast on October 25, at 8:30am EDT / 2:30 pm CEST highlights the top-line results and plans for future approval and launch in 2022. Gil Beyen, CEO, Eric Soyer, CFO/COO, and Iman El-Hariry, CMO, will deliver a brief presentation, followed by a Q&A session.

The audio call is accessible via the below registering link: View Source (Conference ID : 2361482). Once registered, participants will receive a unique access code and the call number details to join the teleconference.
The webcast can be followed live online via the link: View Source
An archive of the webcast will be available on ERYTECH’s website, under the "Investors" section at investors.erytech.com

An archived replay of the audio call will be available for 7 days by dialing + 1 855 859 2056, Conference ID: 2361482#.