On September 16, 2024 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on liver-directed cancer therapies, reported the presentation of new subgroup analysis data from the FOCUS Phase 3 trial of HEPZATO KIT (melphalan/Hepatic Delivery System (HDS)) in patients with metastatic uveal melanoma (mUM) (Press release, Delcath Systems, SEP 16, 2024, View Source [SID1234646648]). The data were presented by Dr. Matthew Wheater from University Hospital Southampton at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Barcelona.

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The FOCUS trial was a pivotal Phase 3 study designed to evaluate the efficacy and safety of HEPZATO KIT in patients with unresectable hepatic metastases from mUM. The primary endpoint of the study was objective response rate (ORR), with secondary endpoints including progression-free survival (PFS) and overall survival (OS). The trial enrolled 102 patients, of whom 91 received treatment. The full results of the FOCUS trial were published on May 4, 2024, in the Annals of Surgical Oncology.

The subgroup analysis evaluated patients with and without extrahepatic disease, treatment-naive versus previously treated patients, and those with low (1-25%) versus high (26-50%) liver tumor burden. There were no significant differences in OS, ORR, or PFS between patients with and without extrahepatic lesions or based on prior therapy. While ORR and PFS remained consistent regardless of liver tumor burden, more extensive liver involvement was associated with worse OS outcomes.

Objective tumor responses were observed throughout the entire treatment period; the earliest following completion of the first treatment cycle, and the latest following treatment cycle 6. This result supports the strategy to continue treatment until best response is achieved. Rates of serious adverse events (SAEs) and Grade 3/4 adverse events (AEs) remained consistent, indicating an absence of cumulative toxicity. These findings underscore the favorable benefit-risk profile of HEPZATO KIT in this patient population, offering a meaningful option for patients who typically have limited treatment options.

Dr. Wheater commented, "The lack of significant differences in outcomes between patients with and without extrahepatic disease is encouraging, particularly for a liver-directed therapy like Melphalan/HDS. Additionally, the fact that responses were observed through all six treatment cycles supports the strategy of continuing treatment beyond two cycles in patients with stable disease."

On September 16, 2024 Cytovation ASA, a clinical stage oncology company focused on the development of its first-in-class bifunctional immunotherapy CY-101 (CyPep-1) reported that it will deliver a poster presentation at ESMO (Free ESMO Whitepaper) 2024 entitled "Safety and activity of CY-101 in patients with advanced solid tumors: the Phase I/IIa CICILIA trial (Press release, Cytovation, SEP 16, 2024, View Source;utm_medium=rss&utm_campaign=cytovation-to-present-full-safety-and-efficacy-data-from-the-cicilia-phase-i-iia-trial-evaluating-cy-101-in-solid-tumors-at-esmo-2024 [SID1234646647])." Data from this study, evaluating intratumoral (IT) administration of CY-101 monotherapy and in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with heavily pretreated advanced solid tumors, show that CY-101 is well tolerated at the recommended Phase 2 dose (RP2D) of 20 mg. Furthermore, these data demonstrate early signs of antitumor activity, especially in tumors with dysregulated Wnt/β-catenin signaling.

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CY-101 is a synthetic peptide with a dual mode of action that both inhibits the oncogenic Wnt/β-catenin pathway by activating Axin2 and has a pore-forming membranolytic effect on cancer cells that exposes antigens and triggers a systemic tumor-specific immune response. Interim results from CICILIA were reported in 2023 (link to press release here) confirming that all trial endpoints were met, with CY-101 demonstrating a consistent safety profile across tumor types and strong early signals of efficacy.

Data from the ESMO (Free ESMO Whitepaper) poster show that no dose-limiting toxicities were observed in the dose- escalation part of the study with the RP2D defined at 20 mg. Analyses of paired tumor biopsies demonstrated induction of cancer cell death in >70% across tumor types at the RP2D, translating to a clinical benefit in several different cancer types. Notably, among six patients with adrenocortical carcinoma (ACC) receiving CY-101 monotherapy, a disease control rate of 50% (n = 3/6) was observed, with durable responses (> 6 months) in two patients. Both patients expressed β-catenin and had somatic mutations in the Wnt/β-catenin pathway.

Separately, the US Food and Drug Administration (FDA) has granted Orphan Drug Designation to CY-101 monotherapy for the treatment of ACC. Orphan Drug Designation is granted to investigational therapies that are intended for the treatment, diagnosis or prevention of rare diseases or conditions that affect fewer than 200,000 people in the US. Orphan Drug Designation provides several benefits to drug developers, including certain development cost benefits in the US, increased FDA interaction and eligibility for seven-year market exclusivity following approval.

"We believe CY-101 is a potentially important new treatment option that offers a truly differentiated approach to targeting Wnt/β-catenin driven cancers, an oncogenic pathway dysregulated in more than 20% of cancers," said Lars Prestergarden, CEO of Cytovation. "Our early data clearly confirm that CY-101 warrants further investigation in larger studies, and we are very pleased to receive Orphan Drug Designation for CY-101 in ACC. We look forward to advancing towards our planned Phase 2 trial in ACC with registrational intent."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merk & Co., Inc., Rahway, NJ, USA.

On September 16, 2024 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported the presentation of longer-term data from its pivotal trial of cosibelimab, its anti-programmed death ligand-1 ("PD-L1") antibody, in locally advanced and metastatic cutaneous squamous cell carcinoma ("cSCC") during the European Society for Medical Oncology ("ESMO") Congress 2024, which is taking place in Barcelona, Spain, from September 13 to 17, 2024 (Press release, Checkpoint Therapeutics, SEP 16, 2024, View Source [SID1234646646]).

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Poster Presentation Title: Cosibelimab in Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Longer-term Efficacy and Safety Results from Pivotal Study

"These longer-term results for cosibelimab presented at the ESMO (Free ESMO Whitepaper) Congress demonstrate a deepening of response over time, with higher objective response and complete response rates than initially observed at the primary analyses, and continue to expand the evidence supporting the efficacy and safety of cosibelimab as a potential new treatment for advanced cSCC," said James Oliviero, President and Chief Executive Officer of Checkpoint. "We look forward to our upcoming December 28, 2024, Prescription Drug User Fee Act ("PDUFA") goal date for our Biologics License Application for cosibelimab, and believe, if approved, cosibelimab’s dual mechanisms of action and safety profile may position the product, over time, as the preferred immunotherapy of U.S. oncologists."

Data highlights include:

Efficacy

With 16 months of additional follow-up since the primary analysis, cosibelimab demonstrated increasing objective response rates ("ORRs") and complete response rates per independent central review in 109 patients with advanced cSCC.
ORRs of 54.8% and 50.0% achieved in locally advanced and metastatic cSCC, with median follow-up durations of 24.1 and 29.3 months, respectively.
Results demonstrate a deepening of response over time, with complete response rates of 25.8% and 12.8% in locally advanced and metastatic cSCC, respectively.
Clinically meaningful durations of response ("DOR") were observed, with median DORs not yet reached in either group.
Safety

Overall, in 192 advanced cSCC patients treated with cosibelimab, a manageable safety profile was observed, with notable low rates of treatment-emergent adverse events ("TEAEs"), severe immune-related adverse events ("irAEs"), and treatment discontinuations.
3.6% of patients experienced an irAE assessed as grade 3, with no observed grade ≥4 irAEs.
No events of grade ≥3 pneumonitis, colitis, hepatitis, nephritis, or endocrinopathies.
Treatment discontinuation due to TEAEs, regardless of attribution, was observed in 12 patients (6.3%); the most common reason was COVID-19/COVID-19 pneumonia (1.6%).
A copy of the poster can be found on the Publications page of the Checkpoint Therapeutics website.

In December 2023, the U.S. Food and Drug Administration ("FDA") issued a complete response letter ("CRL") for the cosibelimab Biologics License Application ("BLA") for the treatment of patients with metastatic or locally advanced cSCC who are not candidates or curative surgery or radiation. The CRL only cited findings that arose during a multi-sponsor inspection of Checkpoint’s third-party contract manufacturing organization ("CMO") as approvability issues to address in a resubmission. In July 2024, Checkpoint announced it had completed a resubmission of the BLA to the FDA for cosibelimab to potentially address the approvability issues cited in the CRL. The resubmission was accepted by the FDA as a complete response and the FDA has set a PDUFA goal date of December 28, 2024.

About Cutaneous Squamous Cell Carcinoma (cSCC)
Cutaneous Squamous Cell Carcinoma is the second most common type of skin cancer in the United States, with an estimated annual incidence of approximately 1.8 million cases according to the Skin Cancer Foundation. Important risk factors for cSCC include chronic ultraviolet exposure and immunosuppressive conditions. While most cases are localized tumors amenable to curative resection, approximately 40,000 cases will become advanced, and an estimated 15,000 people will die from this disease each year. In addition to being a life-threatening disease, cSCC causes significant functional morbidities and cosmetic deformities based on tumors commonly arising in the head and neck region and invading blood vessels, nerves and vital organs such as the eye or ear. The immune-suppressed population represents a challenging target in the treatment of advanced cSCC, as they present with a more aggressive disease and with a higher risk of developing immune-related toxicities from checkpoint inhibitor treatment.

About Cosibelimab
Cosibelimab is a potential differentiated, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to PD-L1 and blocks the PD-L1 interaction with the programmed death receptor-1 ("PD-1") and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained high tumor target occupancy of PD-L1 to reactivate an antitumor immune response and the additional potential benefit of a functional Fc domain capable of inducing antibody-dependent cellular cytotoxicity ("ADCC") for potential enhanced efficacy.

On September 16, 2024 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address oncological and inflammatory diseases, reported that it received approval from the Israeli Ministry of Health (MoH) to conduct Phase IIa clinical trial with orally-administered Namodenoson in the treatment of pancreatic carcinoma (Press release, Can-Fite BioPharma, SEP 16, 2024, View Source [SID1234646645]).

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"We are very much encouraged by the excellent data in the pre-clinical studies demonstrating the impressive anti-cancer effect of namodenoson and definitive molecular mechanism of action against pancreatic carcinoma," stated Dr. Fishman, Can-Fite’s Chief Scientific Officer and Executive Chairman. "We are very keen to initiate the study in this devastating disease and are pleased with the regulatory approval of the Israeli MOH. We do hope that as we have shown efficacy in patients with advanced liver cancer studies, we will be able to demonstrate safety and efficacy in the pancreatic cancer patient population."

The Phase IIa is a multicenter open-label trial in patients with advanced pancreatic adenocarcinoma whose disease has progressed on at least 1st-line therapy. The trial will evaluate the safety, clinical activity, and pharmacokinetics (PK) of Namodenoson in this patient population. All patients will receive oral Namodenoson 25 mg, administered twice daily for consecutive 28-day cycles. Patients will be evaluated regularly for safety. Approximately 20 evaluable patients will be enrolled. The primary objective of this trial is to characterize the safety profile of Namodenoson and the secondary objective is to evaluate the clinical activity as determined by the Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), Progression-Free Survival (PFS), Disease Control Rate (DCR), Duration of Response (DoR), and Overall Survival (OS).

The study will be conducted by Dr. Stemmer, a leading key opinion leader, at the Institute of Oncology, Rabin Medical Center, Israel and by Dr. Al Mutar from the UT Southwestern Medical Center in the US.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.

On September 16, 2024 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a clinical-stage global biopharmaceutical company developing innovative cancer therapies, reported interim phase 2 data on the 303 Study, a study in 2L/3L non-small cell lung cancer (NSCLC) after disease progression on 1L PD-1/L1 inhibitors with and without chemotherapy, with financial support from Merck & Co., Inc’s (NYSE: MRK, known as MSD outside of the United States and Canada) Investigator Studies Program and provision of study drug, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024, on September 14, 2024 in Barcelona, Spain (Press release, BeyondSpring Pharmaceuticals, SEP 16, 2024, View Source;utm_medium=rss&utm_campaign=beyondspring-presents-efficacy-safety-results-from-a-phase-2-study-of-pembrolizumab-plus-plinabulin-docetaxel-in-metastatic-nsclc-after-progressing-on-first-line-immune-checkpoint-inhibitors-at-esmo-c [SID1234646644]).

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Docetaxel remains the standard of care for patients with 2L/3L NSCLC without targetable alterations who progress on 1L immune checkpoint inhibitors (ICI) with and without standard chemotherapy, with an overall response rate (ORR) of 12.8% and median PFS (mPFS) of 3.7 months in TROPION Lung-01 phase 3 studies. In metastatic NSCLC resistant to previous PD-1/L1 therapy1, PD-L1 and CTLA-4 inhibition alone or in combination with hypofractionated radiotherapy produced limited clinical benefits with ~11.5% ORR.

This investigator-initiated, single-arm, open-label, phase 2 study (KeyPelms-004 or 303 Study) evaluates the efficacy and safety of a triple combination regimen of pembrolizumab plus plinabulin/docetaxel (NCT05599789). The study intends to enroll a total of 47 patients and is ongoing at Peking Union Medical College Hospital, Beijing, China with the principal investigator Dr. Mengzhao Wang, Chief of the Department of Respiratory and Critical Care Medicine. Here, we report on a planned formal interim analysis of 19 patients.

At the database lock on 29 April 2024, 29 patients were enrolled and 19 were evaluable for stage 1 data analysis. All patients experienced disease progression after initial clinical benefit with ICI. Of the 19 evaluable patients (median age at 66.4 years; ranged 50-76 years), 68.4% were male and 31.6% were female; 57.9% were current or former smokers. Histology included 57.9% patients with non-squamous cell carcinoma and 42.1% with squamous cell carcinoma. The median follow-up was 8.67 months. Below is an efficacy summary table.

Primary Endpoint Plinabulin + Pembrolizumab + Docetaxel (n=19)
Confirmed ORR (RECIST 1.1) 21.1%
Secondary Endpoints
Median PFS (RECIST 1.1) 8.63 M
(6 M PFS rate: 67.1%;

12 M PFS rate: 49.2%)

Median OS
(Overall Survival)

Not reached
Median DoR
(Duration of Response)

11.40 M
Disease Control Rate
(PR + SD > 4 months)

89.5%
The combination was well tolerated. 6% of patients experienced grade 3 or higher treatment-related adverse effects. There were no treatment-related deaths.
"Plinabulin is a potent inducer of dendritic cell or DC maturation that leads to T cell activation. DC is the most potent antigen presenting cell (APC). This unique mechanism of action reinforces anti-tumor immune response with the potential to overcome acquired ICI resistance, which may derive from APC pathway mutation or T cell exhaustion. Compared to historical controls of 3-4 months of median PFS2, this study’s early efficacy data doubled median PFS to 8.6 months, with an impressive disease control rate of almost 90%, which is encouraging and clinically meaningful for this severe unmet need," said Dr. Mengzhao Wang, principal investigator at Peking Union Medical College Hospital.

ESMO Congress 2024 (1330P): Phase 2 Study of Pembrolizumab plus Plinabulin and Docetaxel for Patients (pts) with Metastatic NSCLC after Failure on First-line Immune Checkpoint Inhibitor Alone or Combination Therapy: Initial Efficacy and Safety Results on Immune Re-sensitization

Presenter: Yan Xu, Peking Union Medical College Hospital, Beijing, China
Poster Session: NSCLC, metastatic

About Plinabulin

Plinabulin is a novel first-in-class dendritic cell maturation therapeutic with durable anti-cancer benefit observed across multiple clinical studies. As a reversible binder at a distinct tubulin pocket, plinabulin does not change tubulin dynamics or antagonize tubulin stabilizing agents, such as docetaxel, which contributes to its differentiated activity and tolerability compared to other tubulin binders. In addition, plinabulin significantly reduces chemotherapy induced neutropenia and could thereby increase docetaxel tolerability. Over 700 patients have been treated with plinabulin with good tolerability.

About KeyPelms-004 or 303 Study

303 Study is an open-label, single-arm Phase 2 Study of Plinabulin plus docetaxel and pembrolizumab for previously treated patients with metastatic NSCLC and progressive disease after anti-PD-(L)1 inhibitor alone or in combination with platinum-doublet chemotherapy. This study evaluates the efficacy and safety of this triple combination and is being conducted at Peking Union Medical College Hospital, Beijing, China. The regimen includes Pembrolizumab 200 mg IV every 3 weeks (Q3W) on Day 1, Docetaxel 75 mg/m2 IV Q3W on Day 1 and Plinabulin 30mg/m2 IV Q3W on Day 1 in a 21-day cycle. The primary endpoint is investigator-based ORR (RECIST 1.1). The secondary endpoints include PFS, OS, DoR, and safety. The study intends to enroll 47 patients with a formal interim analysis of 19 patients enrolled. The study is funded by Merck’s Investigator Studies Program with provision of study drug and financial support.