On October 17, 2023 Defence Therapeutics Inc. ("Defence" or the "Company"), a Canadian biopharmaceutical company specialized in the development of immune-oncology vaccines and drug delivery technologies, reported that systemic administration of novel AccuTOXTM-chitosan encapsulated formulation inhibits the growth of pre-established solid lymphoma resulting in their progressive shrinking overtime (Press release, Defence Therapeutics, OCT 17, 2023, View Source;utm_medium=rss&utm_campaign=delivery-of-encapsulated-accutoxtm-chitosan-nanoparticles-triggers-complete-tumor-regression-in-animals-with-pre-estabslihed-solid-lymphoma [SID1234636061]).

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The conducted study had two main objectives: i) to test whether AccuTOXTM can be delivered systemically if encapsulated in chitosan-based nanoparticles, and ii) to assess whether this modality can synergize with immune-checkpoint blockers commonly used in the oncology clinic. The formulation was delivered twice with a 2 weeks interval and treated animals were followed for up to 40 days. The tumors in animals treated with AccuTOXTM-Chitosan injections along with anti-PD-1 co-administration regressed and exhibited a prolonged survival rate.

"The AccuTOXTM molecule can be toxic if delivered unconjugated and/or systemically. The Defence team was able to bypass this limitation by encapsulating it into chitosan-based nanoparticles. This is a simpler and cheaper method compared to the use of antibodies, and may represent a key component of Defence’s future encapsulation strategies", says Mr. Plouffe, CEO of Defence Therapeutics.

Chitosan is a linear polysaccharide composed of randomly distributed β-(1→4)-linked D-glucosamine (deacetylated unit) and N-acetyl-D-glucosamine (acetylated unit), and has a number of commercial and biomedical uses. In addition to its agricultural and industrial applications, chitosan is often useful in bandages to reduce bleeding and as an antibacterial agent. It can also be used to help deliver drugs through the skin. Therefore, exploiting it as a delivery vehicle for unconjugated Accum or its variants could revolutionize the future of molecular medicine by increasing the compounds specificity to tumor site while minimizing the needed dosage and thus, associated side effects.

On October 17, 2023 CytoAgents, Inc., a clinical-stage biotechnology company developing a safe, effective treatment for Cytokine Release Syndrome (CRS), reported that it has initiated recruitment and will enroll its first patient at UPMC Hillman Cancer Center, in the Phase 1b/2a clinical trial evaluating the therapeutic, CTO1681, to treat CRS in lymphoma patients receiving CAR T-cell Therapy (Press release, CytoAgents, OCT 17, 2023, View Source [SID1234636060]).

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"This clinical trial (CTA-2101) addresses an area of great unmet medical need as the majority of patients receiving CAR T-cell Therapy experience the toxicities of CRS and associated neurotoxicity," said Arthur P. Bertolino, MD, PhD, MBA, Chief Medical Officer at CytoAgents.

The clinical trial will be conducted at multiple U.S. sites, with UPMC Hillman Cancer Center now the initial enrolling site. The trial investigates the safety, tolerability, and efficacy of different doses of CTO1681 in lymphoma patients receiving CAR T-cell therapy.

"We were early adopters of CAR T-cell therapy and remain committed to providing this treatment for our patients in the safest way possible," said Robert L. Ferris, M.D., Ph.D., a physician-scientist, and director of UPMC Hillman Cancer Center. "We are dedicated to solving the CRS problem associated with CAR T-cell therapy and to be a part of this clinical trial at our institution."

CytoAgents is developing innovative pharmaceutical products to treat life-threatening conditions, diseases and disorders associated with CRS, commonly referred to as cytokine storm. CRS is caused by excessive cytokine production and can be triggered by a range of diseases and treatments. Certain advanced immunotherapies in the oncology space such as CAR T-cell and Bispecific Antibody Therapies suffer from high incidence of associated CRS. The company expects that effective CRS management will support greater accessibility to and broader adoption of these highly effective therapies in the clinic.

"We are thrilled to advance CTO1681 into the clinic to establish key insights into the safety and efficacy of our novel therapeutic," said Teresa Whalen, RPh, CEO at CytoAgents. "Dosing our first patients in the lymphoma population is an important step forward for the company and the patients who may benefit. We look forward to continued enrollment with data anticipated in 2024."

Details of the CTA-2101 trial can be found at www.clinicaltrials.gov under the identifier NCT05905328.

On October 17, 2023 Bristol Myers Squibb (NYSE: BMY) reported three-year follow-up results from exploratory analyses of the Phase 3 CheckMate -816 trial, demonstrating sustained event-free survival (EFS) and promising overall survival (OS) trends with three cycles of Opdivo (nivolumab) in combination with platinum-based chemotherapy for the neoadjuvant treatment of patients with resectable non-small cell lung cancer (NSCLC), regardless of PD-L1 expression levels (Press release, Bristol-Myers Squibb, OCT 17, 2023, View Source;816-Trial/default.aspx [SID1234636059]). Neoadjuvant Opdivo with chemotherapy also showed improvements in pathologic complete response (pCR) and major pathologic response (MPR) over chemotherapy alone in PD-L1 ≥1% and <1% patient populations. The safety profile of the Opdivo-based regimen was consistent across all PD-L1 subgroups. These results will be featured in a late-breaking oral presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 on October 23, 2023, from 8:45 a.m. to 9:55 a.m. EDT / 14:45 to 15:55 CEST (Abstract #LBA57).

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"The three-year results with neoadjuvant nivolumab with chemotherapy are a continuation of the statistically significant and clinically meaningful results we have seen with this regimen in the treatment of resectable non-small cell lung cancer, and they provide hope for patients that they may achieve long-term benefit," said Mariano Provencio Pulla, M.D., Ph.D., Medical Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain. "It is encouraging to see that this neoadjuvant immunotherapy combination has demonstrated improvements across efficacy measures, regardless of PD-L1 expression levels, including within the PD-L1 negative subgroup that faces high unmet needs and represents approximately 40% of the study population. The CheckMate -816 data clearly indicate the potential for better outcomes for patients with this regimen than chemotherapy alone."

With a median follow-up of 41.4 months in the CheckMate -816 trial, exploratory analyses showed:

OS: While OS remains immature at this follow-up, promising OS trends were seen in both PD-L1 ≥1% and <1% patient populations. For patients with tumor PD-L1 expression ≥1%, Opdivo with chemotherapy reduced the risk of death by 63% (Hazard Ratio [HR] 0.37; 95% Confidence Interval [CI]: 0.20 to 0.71). Three-year OS rates favored neoadjuvant Opdivo with chemotherapy over chemotherapy alone at 85% vs. 66%, respectively. In patients with PD-L1 <1%, Opdivo with chemotherapy reduced the risk of death by 19% (HR 0.81; 95% CI: 0.48 to 1.36), with three-year OS rates being 71% vs. 60%.
EFS: Among patients with tumor PD-L1 expression ≥1%, three-year EFS rates were 72% with neoadjuvant Opdivo with chemotherapy vs. 47% with chemotherapy alone (HR 0.46; 95% CI: 0.28 to 0.77). In patients with tumor PD-L1 expression <1%, EFS rates were 42% with the combination vs. 39% with chemotherapy (HR 0.87; 95% CI: 0.57 to 1.35).
pCR: In patients with PD-L1 ≥1%, pCR rates were 32.6% with neoadjuvant Opdivo with chemotherapy compared to 2.2% with chemotherapy alone. For those with PD-L1 <1%, pCR rates were 16.7% vs. 2.6%, respectively.
MPR: Among patients with PD-L1 ≥1%, MPR rates with neoadjuvant Opdivo with chemotherapy were 44.9% vs. 5.6% with chemotherapy. For patients with PD-L1 <1%, MPR rates were 29.5% with the Opdivo-based regimen and 14.3% with chemotherapy alone.
Definitive Surgery: Definitive surgery rates with Opdivo with chemotherapy vs. chemotherapy were 84% vs. 74% in patients with tumor PD-L1 expression ≥1% and 81% vs. 77% in patients with tumor PD-L1 expression <1%. Of these, complete resection was achieved in 91% vs. 82% and 79% vs. 76% of cases, respectively.
"At ESMO (Free ESMO Whitepaper) this year, we are presenting data from several trials across stages and treatment settings in non-small cell lung cancer, including two studies in resectable disease. This is an area of research that we are heavily committed to, as it presents an important opportunity to treat cancer at earlier stages when the tumor is most responsive to treatment and the patient’s immune system is most intact," said Abderrahim Oukessou, M.D., vice president, thoracic cancers global program lead, Bristol Myers Squibb. "We are thrilled to see consistent results with the neoadjuvant regimen of Opdivo with chemotherapy from the CheckMate -816 study, regardless of PD-L1 expression, which build on the benefits we have already seen that led to multiple approvals of this combination globally. We want to sincerely thank every patient and investigator involved in the clinical trial."

Opdivo and Opdivo-based combinations have shown improved efficacy in the neoadjuvant, adjuvant or perioperative treatment of four earlier-stage tumor types, including lung cancer, bladder cancer, esophageal/gastroesophageal junction cancer and melanoma.

About CheckMate -816

CheckMate -816 is a Phase 3 randomized, open label, multi-center trial evaluating Opdivo with chemotherapy compared to chemotherapy alone as neoadjuvant treatment in patients with resectable stage IB to IIIA non-small cell lung cancer (per the 7th edition American Joint Committee on Cancer/Union for International Cancer Control staging criteria), regardless of PD-L1 expression. For the primary analysis, 358 patients were randomized to receive either Opdivo 360 mg plus histology-based platinum doublet chemotherapy every three weeks for three cycles, or platinum doublet chemotherapy every three weeks for three cycles, followed by surgery. The primary endpoints of the trial are event-free survival and pathologic complete response. Secondary endpoints include overall survival, major pathologic response, and time to death or distant metastases.

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Non-metastatic cases account for the majority of NSCLC diagnoses (approximately 60%, with up to half of these being resectable), and the proportion is expected to grow over time with enhanced screening programs. While many non-metastatic NSCLC patients are cured by surgery, 30% to 55% develop recurrence and die of their disease despite resection, contributing to a need for treatment options administered before surgery (neoadjuvant) and/or after surgery (adjuvant) to improve long-term outcomes.

On October 17, 2023 Bristol Myers Squibb (NYSE: BMY) reported the first presentation of results from the Phase 3 CheckMate -901 trial, in which Opdivo (nivolumab) in combination with cisplatin-based chemotherapy followed by Opdivo monotherapy demonstrated statistically significant and clinically meaningful improvements in the primary efficacy endpoints of overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR) compared to standard-of-care cisplatin-based chemotherapy as a first-line treatment for patients with unresectable or metastatic urothelial carcinoma who are cisplatin-eligible (Press release, Bristol-Myers Squibb, OCT 17, 2023, View Source;901-Trial/default.aspx [SID1234636058]).

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With a median follow-up of approximately 33 months, treatment with Opdivo in combination with cisplatin-based chemotherapy reduced the risk of death by 22%, demonstrating a median OS of 21.7 months vs. 18.9 months with chemotherapy alone (Hazard Ratio [HR] 0.78; 95% Confidence Interval [CI]: 0.63 to 0.96; p=0.0171). At the 12- and 24-month landmark analyses, patients treated with upfront Opdivo plus chemotherapy experienced OS rates of 70.2% and 46.9%, respectively, compared to 62.7% and 40.7% with chemotherapy. In patients receiving the Opdivo-based combination, the risk of death or disease progression was reduced by 28%, with median PFS at 7.9 months compared to 7.6 months with chemotherapy (HR 0.72; 95% CI: 0.59 to 0.88; p=0.0012). The landmark 12- and 24-month PFS rates were 34.2% and 23.5%, compared to 21.8% and 9.6% with chemotherapy. The combination of Opdivo with cisplatin-based chemotherapy had a tolerable safety profile consistent with the known safety profiles of the individual components of the regimen. No new safety concerns have been identified.

Additionally, in exploratory analyses, Opdivo with cisplatin-based chemotherapy resulted in an approximately 15% higher objective response rate (ORR) compared to chemotherapy alone (57.6% vs. 43.1%), and nearly doubled the number of patients who achieved a complete response (CR; 21.7% vs. 11.8%). Opdivo in combination with cisplatin-based chemotherapy was associated with longer duration of response than chemotherapy, and median duration of complete response was nearly tripled (37.1 months vs. 13.2 months).

The first disclosure of these data will be featured in a Presidential Symposium during the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 on October 22, 2023, from 10:30 a.m. to 12:15 p.m. EDT / 16:30 to 18:15 CEST (Abstract #LBA7).

"In patients with metastatic urothelial carcinoma, we often see poor durability of responses with chemotherapy alone in the first-line treatment setting. This has long been a major challenge in the treatment of patients with this hard-to-treat disease," said Michiel S. van der Hejiden, M.D., Ph.D., Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands. "This survival benefit seen with nivolumab in combination with cisplatin-based chemotherapy represents a momentous accomplishment that may provide hope for urothelial cancer patients as the first concurrent chemo-immunotherapy combination to demonstrate such an improvement compared to standard-of-care cisplatin-based combinations. The implications of these data have the potential to be practice-changing and transform the way cisplatin-eligible patients are treated."

"Historically, there have been no effective immunotherapy-based options available in the front-line setting for patients with unresectable or metastatic urothelial carcinoma who are cisplatin-eligible. We are proud to see these results demonstrating that Opdivo with cisplatin-based chemotherapy may provide patients hope and offer survival benefits with this immunotherapy approach," said Dana Walker, M.D., M.S.C.E., vice president, global program lead, genitourinary cancers, Bristol Myers Squibb. "The CheckMate -901 results bolster our existing body of research, which has shown overall survival improvements with Opdivo-based treatments across multiple tumor types, including in genitourinary cancers. We look forward to discussing these data with global health authorities in the coming months and have great hope that we may potentially provide these patients with a new and much needed treatment regimen."

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -901 clinical trial.

Opdivo and Opdivo-based combinations have shown significant improvements in OS in Phase 3 clinical trials across several tumors, including metastatic urothelial carcinoma, advanced renal cell carcinoma, non-small cell lung cancer, malignant pleural mesothelioma, metastatic melanoma and esophageal squamous cell carcinoma.

About CheckMate -901

CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy or Opdivo in combination with cisplatin-based chemotherapy followed by Opdivo monotherapy compared to standard-of-care chemotherapy alone, in patients with untreated unresectable or metastatic urothelial cancer.

In the CheckMate -901 study, evaluating Opdivo with cisplatin-based chemotherapy vs. standard-of-care chemotherapy, a total of 608 patients eligible for cisplatin-based chemotherapy were randomized to receive either Opdivo 360 mg in combination with cisplatin-based chemotherapy every 3 weeks or chemotherapy alone followed by 480mg/Q4 Opdivo monotherapy until disease progression or death up to a maximum of two years. The primary endpoints of this study are overall survival (OS) and progression-free survival (PFS). The study is ongoing to assess Opdivo plus Yervoy vs. standard-of-care chemotherapy.

The OS and PFS outcomes for patients who are eligible for cisplatin-based chemotherapy are based on the final efficacy analyses of these endpoints.

About Urothelial Carcinoma

Bladder cancer is the 10th most common cancer in the world, with more than 573,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but approximately 50% of patients who undergo surgery will experience disease progression and recurrence within two-to-three years post-surgery. Approximately 20% to 25% of patients with urothelial carcinoma develop metastatic disease. The poor durability of responses seen with chemotherapy alone in the first-line setting presents a major challenge in the treatment of metastatic disease, and there are limited treatment options in the second-line setting for patients with advanced urothelial carcinoma.

On October 17, 2023 Bristol Myers Squibb (NYSE: BMY) reported the first disclosure of data from the Phase 3 CheckMate -77T trial evaluating the perioperative regimen of neoadjuvant Opdivo (nivolumab) with chemotherapy followed by surgery and adjuvant Opdivo in patients with resectable stage IIA to IIIB non-small cell lung cancer (NSCLC) (Press release, Bristol-Myers Squibb, OCT 17, 2023, View Source;77T-Trial/default.aspx [SID1234636057]). In the study, the perioperative regimen showed a statistically significant and clinically meaningful improvement in the primary efficacy endpoint of event-free survival (EFS) as assessed by Blinded Independent Central Review (BICR) compared to neoadjuvant chemotherapy and placebo followed by surgery and adjuvant placebo.

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With a median follow-up of 25.4 months, in patients treated with neoadjuvant Opdivo and chemotherapy followed by surgery and adjuvant Opdivo, the risk of disease recurrence, progression or death was reduced by 42% (EFS Hazard Ratio [HR] 0.58; 97.36% Confidence Interval [CI]: 0.42 to 0.81; p=0.00025). Additionally, neoadjuvant Opdivo and chemotherapy showed improvements in the secondary efficacy endpoints of pathologic complete response (pCR; 25.3% vs. 4.7%) and major pathologic response (MPR; 35.4% vs 12.1%). The study is ongoing to assess its other secondary endpoint of overall survival (OS). Definitive surgery rates were 78% with the Opdivo-based regimen vs. 77% with chemotherapy and placebo, with complete resection achieved in 89% vs. 90% of patients, respectively. The safety profile of the Opdivo-based regimen was consistent with previously reported studies in NSCLC. No new safety signals were identified.

The first disclosure of these data will be featured in a Presidential Symposium during the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 on October 21, 2023, from 10:30 a.m. to 12:15 p.m. EDT / 16:30 to 18:15 CEST (Abstract #LBA1).

"Over the past few years, we have witnessed incredible progress in the treatment of patients with non-metastatic non-small cell lung cancer. Now, we are evaluating therapeutic strategies that expand on these advances with the goal of providing clinical benefit to a greater number of patients with resectable disease," said Tina Cascone, M.D., Ph.D., associate professor of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center. "I am extremely encouraged by the findings of CheckMate -77T evaluating neoadjuvant nivolumab and chemotherapy followed by surgery and adjuvant nivolumab, and by how continuing adjuvant nivolumab after surgery may further improve outcomes and provide a potentially more durable benefit for our patients. The results from the CheckMate -77T study are promising for physicians, patients and their families alike. I look forward to seeing how the data from this ongoing trial continues to unfold, especially the secondary endpoint of overall survival."

"The results from the CheckMate -77T study add to the evidence supporting the use of Opdivo-based therapies in resectable non-small cell lung cancer and reinvigorate our commitment to treating cancer at earlier stages of the disease in the hopes of helping patients attain durable benefit," said Abderrahim Oukessou, M.D., vice president, thoracic cancers global program lead, Bristol Myers Squibb. "We are pleased to be presenting research from multiple trials in resectable NSCLC at ESMO (Free ESMO Whitepaper), building on our deep scientific understanding of thoracic cancer treatment. We look forward to upcoming discussions with regulatory authorities and hope that we may offer yet another option to patients with non-metastatic NSCLC that could potentially reduce their risk of disease recurrence, progression or death, and lead to better long-term outcomes."

To date, Opdivo and Opdivo-based combinations have shown improved efficacy in the neoadjuvant, adjuvant or perioperative treatment of four tumor types: lung cancer, bladder cancer, esophageal/gastroesophageal junction cancer and melanoma.

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -77T clinical trial.

About CheckMate -77T

CheckMate -77T is a Phase 3 randomized, double-blind, placebo-controlled, multi-center trial evaluating neoadjuvant Opdivo with chemotherapy followed by surgery and adjuvant Opdivo versus neoadjuvant chemotherapy and placebo followed by surgery and adjuvant placebo in 452 patients with resectable stage IIA to IIIB non-small cell lung cancer (NSCLC). The primary endpoint of the trial is event-free survival (EFS). Secondary endpoints include overall survival (OS), pathologic complete response (pCR) and major pathologic response (MPR).

About Lung Cancer

Lung cancer is the leading cause of cancer deaths globally. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Non-metastatic cases account for the majority of NSCLC diagnoses (approximately 60%, with up to half of these being resectable), and the proportion is expected to grow over time with enhanced screening programs. While many non-metastatic NSCLC patients are cured by surgery, 30% to 55% develop recurrence and die of their disease despite resection, contributing to a need for treatment options administered before surgery (neoadjuvant) and/or after surgery (adjuvant) to improve long-term outcomes.