On January 16, 2024 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported the first commercial use of HEPZATO KIT for the treatment of metastatic uveal melanoma (mUM) (Press release, Delcath Systems, JAN 16, 2024, https://delcathsystemsinc.gcs-web.com/news-releases/news-release-details/delcath-systems-announces-us-launch-and-first-commercial [SID1234639256]).

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The procedure took place at Moffitt Cancer Center in Tampa, Florida by Dr. Jonathan S. Zager, M.D., Chief Academic Officer; Senior Member, Department of Cutaneous, Oncology; Director of Regional Therapies, Moffitt Cancer Center. Dr. Zager was the global Lead Investigator for the FOCUS Phase 3 trial.

"The fact that patients with difficult to treat metastatic uveal melanoma with limited treatment options now have another alternative is truly remarkable and exciting. There has been a large unmet need for liver directed therapy options to treat this patient population and we intend to incorporate this as standard of care for appropriate patients," said Dr. Zager. Dr. Zager enrolled and treated the first and last patients on the FOCUS Phase 3 trial and the team at Moffitt has performed the procedure over 200 times to date.

The company is working with numerous other leading cancer centers across the U.S. which have indicated interest in HEPZATO KIT to ensure patients nationwide have access to this important treatment. In conjunction with the first commercial treatment, Delcath also launched websites relating to the HEPZATO KIT, including HEPZATO KIT, HEPZATO KIT REMS, and HEPZATO KIT Access, to support the commercial launch.

"The first commercial procedure utilizing HEPZATO KIT in the U.S. is a significant milestone for Delcath and patients suffering from metastatic uveal melanoma. We are proud to continue our relationship with Dr. Zager and the team at Moffitt Cancer Center to bring this unique treatment to appropriate patients in need. I want to thank all the collaborators and patients who participated in the long but necessary process to bring HEPZATO KIT to market," said Gerard Michel, Delcath’s Chief Executive Officer.

About HEPZATO KIT

HEPZATO KIT (melphalan for Injection/Hepatic Delivery System), approved for use in the United States by FDA, is a combination drug/device product which administers HEPZATO (melphalan) directly to the liver through the HDS, which permits higher drug exposure in target tissues while limiting systemic toxicity.

HEPZATO KIT is approved in the United States as a liver-directed treatment for adult patients with uveal melanoma with unresectable hepatic metastases affecting less than 50% of the liver and no extrahepatic disease, or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation.

HEPZATO KIT Important Safety Information
Patients eligible for HEPZATO KIT should NOT have any of the following medical conditions:

Active intracranial metastases or brain lesions with a propensity to bleed
Liver failure, portal hypertension, or known varices at risk for bleeding
Surgery or medical treatment of the liver in the previous 4 weeks
Active cardiac conditions including unstable or severe angina or myocardial infarction), worsening or new-onset congestive heart failure, significant arrhythmias, or severe valvular disease
History of allergies or known hypersensitivity to melphalan or a component or material utilized within the HEPZATO KIT including natural rubber latex, heparin, and severe hypersensitivity to iodinated contrast not controlled by antihistamines and steroids
Most common adverse reactions or laboratory abnormalities occurring with HEPZATO KIT treatment are thrombocytopenia, fatigue, anemia, nausea, musculoskeletal pain, leukopenia, abdominal pain, neutropenia, vomiting, increased alanine aminotransferase, prolonged activated partial thromboplastin time, increased alkaline phosphatase, increased aspartate aminotransferase and dyspnea.

Severe peri-procedural complications including hemorrhage, hepatocellular injury, and thromboembolic events may occur via hepatic intra-arterial administration of HEPZATO. HEPZATO KIT is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the HEPZATO KIT REMS. Myelosuppression with resulting severe infection, bleeding, or symptomatic anemia may occur with HEPZATO. Additional cycles of HEPZATO KIT therapy will be delayed until blood counts have improved.

Please see the full Prescribing Information, including BOXED WARNING for the HEPZATO KIT.

On January 16, 2024 Halozyme Therapeutics, Inc. (NASDAQ: HALO) ("Halozyme") reported that Roche received European Commission (EC) marketing authorization of Tecentriq SC (atezolizumab) co-formulated with ENHANZE, Halozyme’s proprietary recombinant human hyaluronidase enzyme, rHuPH20 (Press release, Halozyme, JAN 16, 2024, View Source [SID1234639276]). The approval applies to all approved indications of Tecentriq IV and represents the European Union (EU)’s first PD-(L)1 cancer immunotherapy for subcutaneous injection.

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Tecentriq SC reduces treatment time to approximately 7 minutes, compared to an IV infusion which can take approximately 30 to 60 minutes. In addition, it may be administered by a healthcare professional outside of the hospital, in a community care setting or at home, depending on national regulations and health systems.

"As the first subcutaneous PD-(L)1 cancer immunotherapy in Europe, Tecentriq SC can provide a new treatment option that can enhance the treatment experience for patients and caregivers while freeing up resources in constrained healthcare systems," said Dr. Helen Torley, president and chief executive officer of Halozyme.

The EC approval follows pivotal data from the Phase IB/III IMscin001 study, which showed comparable levels of Tecentriq in the blood, when administered subcutaneously, and a safety and efficacy profile consistent with the IV formulation. The study found 90% of healthcare professionals agreed that the SC formulation is easy to administer and 75% said it could save time for healthcare teams compared with the IV formulation.

On January 16, 2024 Presage Biosciences, a biotechnology company whose mission is to enable precision drug response evaluation in the human tumor microenvironment (TME), reported that the U.S. Food and Drug Administration (FDA) has issued a Study May Proceed notification for testing a pre-GMP drug candidate with the CIVO platform (Press release, Presage Biosciences, JAN 16, 2024, View Source [SID1234639277]). The drug candidate, PBA-0405, is owned by Poland-based biopharmaceutical company, Pure Biologics, and represents the earliest stage material to date that will be evaluated in patients in a CIVO Phase 0 clinical trial. PBA-0405 is a ROR1-targeting compound that has been engineered to induce tumor cell killing by cytotoxic immune cells.

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"We are very excited by this first opportunity to evaluate pre-GMP material in partnership with Pure Biologics," said Patrick Gray, PhD, Presage CEO. "This is a tremendous step forward for both Presage and overall drug development. We continue to push the bounds on finding alternatives to using preclinical models that fail to capture the effects of novel agents in the intact TME."

"The Pure Biologics team is incredibly proud of this momentous achievement," said Dr. Filip Jelen, Pure Biologics Co-Founder and President of the Management Board." "Our partnership with Presage was key in achieving this milestone and we eagerly await the first insights into drug efficacy and impact on the tumor microenvironment."

About CIVO
Comparative In Vivo Oncology (CIVO) is Presage’s patented platform that enables multiplexed intratumoral microdosing and generation of detailed tumor profiling. The CIVO device can deliver up to eight different drugs or drug combinations simultaneously into trackable drug columns. Presage’s CIVO technology and analysis capabilities are unparalleled at providing insight into drug-exposed areas of the intact tumor microenvironment. Presage is pairing the use of CIVO with molecular profiling technologies in both preclinical and Phase 0 trials in order to inform and de-risk oncology drug development.

On January 16, 2024 Ferring Pharmaceuticals reported that ADSTILADRIN (nadofaragene firadenovec-vncg) is now fully available across the U.S. for healthcare providers to prescribe for their adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors (Press release, Ferring, JAN 16, 2024, View Source [SID1234639258]). Approved by the U.S. Food & Drug Administration (FDA) in December 2022, ADSTILADRIN is the first and only FDA-approved intravesical gene therapy for adults with NMIBC who no longer respond to standard therapy.

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"From the day we received FDA approval, Ferring has been committed to making
ADSTILADRIN available to every appropriate high-risk NMIBC patient quickly and responsibly, working collaboratively with the bladder cancer community to inform our approach," said Bipin Dalmia, Senior Vice President, Global Head, Uro-Oncology Franchise at Ferring Pharmaceuticals. "With our significant manufacturing investments, we have achieved full product supply ahead of schedule. We are therefore ending our ADSTILADRIN Early Experience Program and look forward to bringing this novel therapy to every patient who needs it"

In September 2023, Ferring initiated the ADSTILADRIN Early Experience Program to a mix of clinical trial sites that participated in the ADSTILADRIN Phase 3 study and community clinics with the highest number of appropriate patients with NMIBC. This temporary program represented Ferring’s commitment to treat as many patients as possible in the short term while ensuring every patient who started on ADSTILADRIN had the ability to continue therapy for the duration of their treatment. Now that full product supply is available ahead of schedule, Ferring can end the temporary ADSTILADRIN Early Experience Program and dramatically increase patient access.

"ADSTILADRIN represents an effective alternative therapy for patients with NMIBC who, historically, had very few options once they no longer responded to standard BCG therapy," said Andrea Maddox-Smith, CEO of the Bladder Cancer Advocacy Network, BCAN. "Increasing access to this innovative therapy offers the potential of what patients need most – safe, effective treatment options that bring hope."

Ferring also initiated a non-interventional study, known as the "ADSTILADRIN in BLadder
CancEr" (ABLE-41) U.S. Real World Evidence (RWE) Study (NCT06026332). This ongoing
study is exploring early utilization, experiences, and outcomes of ADSTILADRIN in the routine care setting.

About ADSTILADRIN
ADSTILADRIN (nadofaragene firadenovec-vncg) is the first and only FDA-approved
intravesical gene-therapy for the treatment of adult patients with high-risk Bacillus CalmetteGuérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors. It is a non-replicating adenovirus vector-based therapy containing the gene interferon alfa-2b, administered by catheter directly into the bladder once every three months. The vector enters the cells of the bladder wall, releasing the active gene and causing the bladder’s cell walls to secrete high quantities of interferon alfa-2b protein, a naturally-occurring protein the body uses to fight cancer. This approach essentially turns the bladder wall cells into interferon microfactories, enhancing the body’s own natural defenses against the cancer.

ADSTILADRIN has been studied in a clinical trial program that includes 157 patients with highgrade, BCG-unresponsive NMIBC who had been treated with adequate BCG previously and did not see benefit from additional BCG treatment (full inclusion criteria published on
clinicaltrials.gov: NCT02773849).1

About Non-Muscle Invasive Bladder Cancer (NMIBC)
NMIBC is a form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.2
Bladder cancer is the sixth most common cancer in the U.S., and it is estimated that there were approximately 81,180 new cases of bladder cancer in the U.S. in 2022,3
75% of which present as NMIBC.4 In patients with high-risk NMIBC, intravesical BCG remains the first-line standard of care. However, more than 50% of patients who receive initial treatment with BCG will experience disease recurrence and progression within one year, with many developing BCG-unresponsive disease.3 Current treatment options for BCG-unresponsive patients are very limited, and National Comprehensive Cancer Network (NCCN) guidelines recommend cystectomy (partial or complete removal of the bladder).5

INDICATION
ADSTILADRIN is a non-replicating adenoviral vector-based gene therapy indicated for the
treatment of adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS: ADSTILADRIN is contraindicated in patients with prior hypersensitivity reactions to interferon alfa or to any component of the product.

WARNINGS AND PRECAUTIONS:

Risk with delayed cystectomy: Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. If patients with CIS do not have a complete response to treatment after 3 months or if CIS recurs, consider cystectomy.
Risk of disseminated adenovirus infection: Persons who are immunocompromised or immunodeficient may be at risk for disseminated infection from ADSTILADRIN due to low levels of replication-competent adenovirus. Avoid ADSTILADRIN exposure to immunocompromised or immunodeficient individuals.
DOSAGE AND ADMINISTRATION: Administer ADSTILADRIN by intravesical instillation only. ADSTILADRIN is not for intravenous use, topical use, or oral administration.

USE IN SPECIFIC POPULATIONS: Advise females of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during ADSTILADRIN treatment and for 3 months after the last dose.

ADVERSE REACTIONS: The most common (>10%) adverse reactions, including laboratory abnormalities (>15%), were glucose increased, instillation site discharge, triglycerides increased, fatigue, bladder spasm, micturition (urination urgency), creatinine increased, hematuria (blood in urine), phosphate decreased, chills, pyrexia (fever), and dysuria (painful urination).

You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-332-1088. You may also contact Ferring Pharmaceuticals at 1-888-FERRING.

Please click to see the full Prescribing Information.

On January 16, 2024 MEI Pharma, Inc. (Nasdaq: MEIP), a clinical-stage pharmaceutical company evaluating novel drug candidates to address known resistance mechanisms to standard-of-care cancer therapies, reported the design of the ongoing Phase 1b study of the mitochondrial oxidative phosphorylation (OXPHOS) inhibitor ME-344 in combination with bevacizumab (Avastin) in refractory metastatic colorectal cancer patients will be presented during a poster session at the 2024 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium to be held January 18 – 20, 2024 (Press release, MEI Pharma, JAN 16, 2024, View Source [SID1234639278]).

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Presentation Title: A Phase 1b Study of the OXPHOS Inhibitor ME-344 in Combination with Bevacizumab in Refractory Metastatic Colorectal Cancer
Session Title: Trials in Progress Poster Session C: Cancers of the Colon, Rectum, and Anus
Presenter: Patrick M. Boland
Date: Saturday, January 20, 2024, 6:30-7:45 AM (Pacific Time)
Abstract Number: TPS222

The poster can be viewed on the MEI Pharma website here:
View Source

About the Phase 1b Study

The ongoing Phase 1b study is evaluating ME-344 plus bevacizumab across two cohorts in patients with metastatic colorectal cancer after failure of standard therapies. The combination of ME-344 and bevacizumab is intended to create metabolic synthetic lethality by leveraging the ability of antiangiogenics like bevacizumab to reduce glycolysis, forcing tumors to switch to mitochondrial respiration via OXPHOS, which is inhibited by ME-344.

In the first cohort of approximately 20 patients ME-344 is administered at 10 mg/kg once weekly for 3 weeks in combination with bevacizumab every two weeks, with cycles repeated every 4 weeks. If the rate of non-progression in Cohort 1 reaches a predetermined progression free survival threshold, Cohort 2 will enroll an additional 20 patients. Patients will be treated until disease progression or intolerability. The primary endpoint of the study is progression free survival. Secondary endpoints include overall response rate, duration of response, overall survival and safety.

The study is being conducted at member centers of the Academic GI Cancer Consortium (AGICC), an oncology consortium dedicated to identifying new drugs to treat gastrointestinal (GI) cancers.

About ME-344

ME-344 is a novel drug candidate that inhibits mitochondrial oxidative phosphorylation (OXPHOS), a fundamental metabolic pathway involved in the production of adenosine triphosphate (ATP) in the mitochondria. ATP provides energy to drive many metabolic cell processes, including division, proliferation, and growth. By disrupting the production of ATP, ME-344 has been shown to induce cancer cell death in nonclinical models and was associated with antitumor activity in clinical studies.

The two main sources of ATP production in cells are OXPHOS and glycolysis; the latter is highly active in most tumors. Anti-angiogenics, like the vascular endothelial growth factor (VEGF) inhibitor bevacizumab (AVASTIN), have the potential to normalize vasculature and decrease reliance on glycolysis. The resulting reduction in glycolysis may trigger an increased dependence on mitochondrial ATP production for energy to support continued tumor proliferation.

In such cases of tumor plasticity, the combination of ME-344 and bevacizumab may induce metabolic synthetic lethality, providing a novel therapeutic strategy. Specifically, leveraging the ability of antiangiogenics like bevacizumab to reduce glycolysis and force tumor cells to switch to mitochondrial respiration via OXPHOS, which is inhibited by ME-344, may reduce access to ATP needed for cell division and growth in tumors.

This approach was first clinically evaluated in a multicenter, investigator-initiated, randomized, open-label, window of opportunity clinical study, evaluating ME-344 (3 doses) plus bevacizumab (1 dose) in 42 women with early HER2-negative breast cancer. Study results demonstrated significant biological antitumor activity as measured by a reduction in the proliferative biomarker Ki-67 compared to placebo. The combination appeared to be generally well tolerated. The data from this study were consistent with preclinical data suggesting that combining ME-344 can augment anti-angiogenic therapy and provided validation for continued evaluation of the combination of ME-344 with bevacizumab and other VEGF inhibitors.

An earlier Phase 1 clinical study evaluating ME-344 as a single-agent in patients with refractory solid tumors also demonstrated anti-tumor activity, further validating the potential of mitochondrial inhibition as a promising therapeutic modality.