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 ScaleReady and Bio-Techne Corporation (NASDAQ: TECH) reported the launch of the G-Rex optimized ProPakTM GMP Cytokines, ideally tailored to high efficiency closed system cell and gene-modified cell therapy (CGT) manufacturing (Press release, Bio-Techne, SEP 16, 2024, View Source [SID1234646664]).

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The ProPakTM GMP Cytokine product consists of a weldable bag filled with liquid formulated GMP-grade cytokines, specifically interleukin-7 (IL-7) or interleukin-15 (IL-15), commonly used in the ex vivo manufacturing of CAR-T and TCR-T cells. The quantity of IL-7 and IL-15 contained in each ProPakTM is sufficient to dose a one (1) liter G-Rex bioreactor at the recommended 10ng/mL concentration. The use of ProPak GMP cytokines will enable manufacturers of CAR-T and TCR-T cell therapies to reduce operating costs and complexity by dramatically simplifying the process of acquiring, storing, preparing, and administering these critical reagents for use in cGMP manufacturing.

"Bio-Techne is deeply committed to highly efficient manufacture of lifesaving cell and gene-modified cell therapies," said Will Geist, President (Protein Sciences) at Bio-Techne Corporation. "ProPakTM GMP Cytokines were optimized for use with the leading G-Rex platform by providing the precise quantity of cytokines needed for highly simplified closed system expansion of CAR-T and TCR-T cell drug products with excellent cell characteristics."

"The G-Rex optimized ProPakTM GMP Cytokine is a differentiated product as it is uniquely designed to enable users of G-Rex to manufacture CAR-T and TCR-T drug products with far more simplicity than is possible with any other cytokine vendor," said Josh Ludwig, Global Commercial Director at ScaleReady. "It eliminates the need for cytokine reconstitution and all of the related headaches in favor of a hands-off ballroom style G-Rex manufacturing approach.

"With the incredible response to our G-Rex Grant Program moving G-Rex into the majority of CGT clinical trials, the G-Rex optimized ProPak is the perfect next step in G-Rex manufacturing simplicity. Grant applicant or not, we will help every G-Rex user cost effectively perform comparability studies to integrate the ProPak GMP Cytokines," concluded Josh Ludwig.

Parties interested in learning more and/or evaluating the ProPakTM GMP Cytokines can reach out to [email protected].

On September 16, 2024 Johnson & Johnson (NYSE: JNJ) reported interim data from the ongoing Phase 2 SunRISe-4 study showing neoadjuvant treatment with investigational TAR-200 plus cetrelimab (CET) achieved nearly double the pathological complete response (pCR) rate compared to CET alone in patients with muscle-invasive bladder cancer (MIBC) who are ineligible or refuse neoadjuvant platinum-based chemotherapy and scheduled for radical cystectomy (RC) (Press release, Johnson & Johnson, SEP 16, 2024, View Source [SID1234646680]). These data were featured as a late-breaking oral presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2024 Congress (Abstract #LBA84).

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"These findings from the SunRISe-4 study show for the first time that an intravesical treatment with TAR-200, combined with a systemic PD-1 inhibitor, could potentially result in a complete pathological response in a high proportion of patients, as well as allowing a tolerable approach," said Andrea Necchi, M.D., of Italy’s Vita-Salute San Raffaele University and the IRCCS San Raffaele Hospital and Scientific Institute and a presenting author of the study. "These preliminary findings show a potential for a future change in the local treatment of muscle-invasive bladder carcinoma using TAR-200."

In the interim analysis of the SunRISe-4 study, neoadjuvant TAR-200 plus CET (n=53) showed overall efficacy with a centrally confirmed pathologic complete response (pCR, [T0]) rate of 42 percent compared to 23 percent (95 percent CI, 28-56; 10-41, respectively) with CET alone (n=31) in patients with histologically proven, non-metastatic MIBC. The pathological overall response (pOR) rate (defined as the proportion of patients ≤ pT1) was 60 percent compared to 36 percent, respectively (CI 95 percent, 46-74; 19-55).1

In a subgroup analysis of patients with organ-confined disease (cT2), those treated with TAR-200 plus CET (n=40) showed a 48 percent pCR rate compared to 23 percent pCR with CET alone (n=26, 95 percent CI, 32-64; 9-44, respectively) and 68 percent were downstaged (≤ pT1) at the time of radical cystectomy, potentially improving surgical outcomes and reducing risk of recurrence.1

"With these promising results, TAR-200 plus cetrelimab as a neoadjuvant therapy before radical cystectomy could potentially alter how bladder cancer is treated," said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Innovative Medicine, Johnson & Johnson. "This investigational innovative approach may offer a possible alternative for many patients who are not eligible for the current standard of pre-operative treatments."

Treatment-related adverse events (TRAEs) occurred in 72 percent of patients treated with TAR-200 combined with CET and 44 percent of patients treated with CET alone, with the majority being Grade 1-2. Nine percent of patients discontinued treatment with TAR-200 and eight percent discontinued treatment with CET in the combined treatment cohort due to TRAEs; no patients discontinued treatment due to TRAEs when treated with CET alone.1

Bladder cancer is the ninth most common cancer in the world.2 Although BCG immunotherapy has been accepted as the standard of care for nearly five decades, 30-40 percent of patients do not respond to BCG and experience disease recurrence or progression.3 In such scenarios, radical cystectomy (removal of the bladder and neighboring structures and organs) emerges as the primary treatment option. This major abdominal procedure requires a urinary diversion to be created to collect and store urine.4

TAR-200 is an investigational targeted releasing system designed to provide extended local release of gemcitabine into the bladder. It is installed in a physician’s office setting during a 2-3 minute procedure with no anesthesia. In December 2023, the FDA granted TAR-200 Breakthrough Therapy Designation (BTD) for the potential future treatment of patients with BCG-unresponsive HR-NMIBC, who are ineligible for or elected not to undergo radical cystectomy (surgical removal of the bladder).

About SunRISe-4
SunRISe-4 (NCT04919512) is an open-label, multicenter, randomized Phase 2 study assessing the efficacy and safety of neoadjuvant TAR-200 + cetrelimab (CET) (anti-programmed death-1 antibody) or neoadjuvant CET alone in patients with MIBC scheduled for RC who are ineligible for or refuse neoadjuvant platinum-based chemotherapy.

About TAR-200
TAR-200 is an investigational targeted releasing system, enabling extended release of gemcitabine into the bladder, increasing the amount of time the drug delivery system spends in the bladder and sustaining local drug exposure. The safety and efficacy of TAR-200 are being evaluated in Phase 2 and Phase 3 studies in patients with MIBC in SunRISe-2 and SunRISe-4, and NMIBC in SunRISe-1, SunRISe-3 and SunRISe-5.

About Cetrelimab
Cetrelimab is an investigational programmed cell death receptor-1 (PD-1) monoclonal antibody being studied for the treatment of bladder cancer, prostate cancer, melanoma, and multiple myeloma as part of a combination treatment. Cetrelimab is also being evaluated in multiple other combination regimens.

About Muscle-Invasive Bladder Cancer
Muscle-invasive bladder cancer (MIBC) is a severe form of bladder cancer where the tumor penetrates the muscular layer of the bladder wall, significantly increasing the risk of metastasis.5 Approximately 25 percent of bladder cancer cases are diagnosed as MIBC at the time of initial presentation.6 Early detection and timely intervention are crucial for managing MIBC, as delayed treatment can lead to poor prognosis.

On September 15, 2024 Genmab A/S reported new data from the Phase 1/2 study of rinatabart sesutecan (Rina-S), an investigational folate receptor-alpha (FRα)-targeted, Topo1 antibody-drug conjugate (ADC), demonstrated a confirmed objective response rate (ORR) of 50.0% (95% CI) in ovarian cancer patients treated with Rina-S 120 mg/m2 once every 3 weeks (Q3W), regardless of FRα expression levels (Press release, Genmab, SEP 15, 2024, View Source [SID1234646610]). These data were from the dose expansion part of a multi-part study evaluating the safety and efficacy of single-agent Rina-S in ovarian cancer (OC) and endometrial cancer (EC). These results, and additional findings from the study, were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 (ESMO) (Free ESMO Whitepaper) in Barcelona, Spain.

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Part B of the study randomized 42 previously-treated patients with histologically or cytologically confirmed advanced OC (epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer) to Rina-S 100 mg/m2 (n=22) or Rina-S 120 mg/m2 (n=20). Ninety-five percent of patients in the 120 mg/m2 group were identified as platinum-resistant ovarian cancer (PROC) as were 90.9% of patients in the 100 mg/m2 group. In patients receiving Rina-S 100 mg/m2, results showed a confirmed ORR of 18.2% compared with 50.0% among patients receiving 120 mg/m2. Results for 100 mg/m2 and 120 mg/m2 respectively also included: complete response: 0 (0%) and 1 (5.6%); partial response in 4 (18.2%) and 8 patients (44.4%); stable disease in 15 (68.2%) and 7 patients (38.9%); disease progression in 3 patients (13.6%) and 1 patient (5.6%). Only one patient in the 120 mg/m2 treatment arm was not evaluable. With a median on study follow-up of 24 weeks, all confirmed responses with the 120 mg/m2 dose were ongoing at the time of data cutoff. The disease control rate (DCR) was 86.4% and 88.9% (95% CI: 65.3-98.6), respectively. Based on these results, Rina-S 120 mg/m2 has been selected for further evaluation in a Phase 3 trial for patients with advanced ovarian cancer, which is expected to start in 2024.

"Ovarian cancer presents a significant challenge, especially for those with advanced or recurrent cases, where treatment options and prognosis are often limited," said Elizabeth Lee, MD, a medical oncologist in the gynecologic oncology program at Dana-Farber. "The encouraging Phase 1/2 data for Rina-S demonstrates the potential for future treatment options for patients. We are looking forward to additional data from tumor-specific dose expansion cohorts."

In this Phase 1/2 study, common treatment-emergent adverse events (TEAEs) included anemia, neutropenia, nausea, thrombocytopenia, leukopenia, fatigue, vomiting, alopecia, and diarrhea. Dose reductions and treatment discontinuations were infrequent. No signals of ocular toxicities, neuropathy or interstitial lung disease (ILD) were observed.

"We are encouraged by the data from this ongoing Phase 1/2 trial evaluating Rina-S in a patient population that is in need of new therapeutic options and believe the data support the potential for Rina-S to demonstrate anti-tumor activity beyond first-generation folate receptor-alpha based therapies," said Jan van de Winkel, Ph.D., President and Chief Executive Officer of Genmab. "Genmab is pioneering technologies that aim to transform the treatment of cancer and other serious diseases. We are committed to evaluating the full potential utility of Rina-S in patients with ovarian, endometrial and other solid tumor cancers."

About Rina-S Phase 1/2 Clinical Trial (NCT05579366)
This open-label, multicenter Phase 1/2 study is designed to evaluate the safety and efficacy of rinatabart sesutecan (Rina-S) as a single agent Q3W at various doses in solid tumors that are known to express FRα. The study consists of multiple parts including Part A dose-escalation cohorts; Part B tumor-specific monotherapy dose-expansion cohorts; Part C platinum-resistant ovarian cancer (PROC) cohort; and Part D combination therapy cohorts.

Part A looked at dose escalation in patients with locally advanced and/or metastatic solid tumors, including epithelial ovarian cancer, endometrial cancer, breast cancer, non-small cell lung cancer, and mesothelioma. In patients with OC (n=32) and EC (n=11), treatment with Rina-S 100-120 mg/m2 (n=23 and n=5, respectively) demonstrated a confirmed Objective Response Rate (ORR) of 30.8% (95% CI: 14.3-51.8) with Partial Responses (PR) in 8 patients (30.8%), Stable Disease (SD) in 15 patients (57.7%), and Progressive Disease (PD) in 3 patients (11.5%). The Disease Control Rate (DCR) was 88.5% (95% CI: 69.8-97.6), and the median Duration of Response (DOR) was 35.3 weeks (95% CI: 20.14-NE).

Part B includes the B1 cohort, which is a dose expansion study in patients with histologically or cytologically confirmed advanced OC (epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer). Patients were randomized 1:1 to 100 mg/m2 and 120 mg/m2 dose groups with a median age ranging from 62.5 to 64.5 years across both groups. Ninety-point nine percent of patients in the 100 mg/m2 group were identified as platinum-resistant ovarian cancer (PROC) as were 95% of patients in the 120 mg/m2 group. Study participants were previously treated with a median of 3 prior lines of therapy (range 1-4) including bevacizumab (90.9% in the 100 mg/m2 group and 90.0% in the 120 mg/m2 group respectively), PARP inhibitors (68.2%; 65%) and mirvetuximab soravtansin (18.2%; 19%). Responses in patients with OC were observed across FRα expression levels.

About Ovarian Cancer
Ovarian cancer is a major global health issue, with over 320,000 new cases diagnosed annually worldwide.i It ranks as the eighth most common cancer and the eighth leading cause of cancer-related deaths among women globally.ii The disease is often diagnosed at an advanced stage due to its subtle and non-specific symptoms, such as abdominal bloating, pelvic pain and difficulty eating.iii Platinum-based chemotherapy, often in combination with targeted therapies and surgery, has been the standard treatment in ovarian cancer across all stages.iv,v Approximately 70-90% of women with advanced-stage ovarian cancer worldwide experience a recurrence after initial treatment.vi Ovarian cancer has a low five-year survival rate, which varies significantly by region, but generally hovers around 30-50%.vii,viii

About Rinatabart Sesutecan (Rina-S; GEN1184)
Rinatabart Sesutecan (Rina-S; GEN1184) is a clinical-stage, FRα-targeted, Topo1 ADC, currently in Phase 2 development for the treatment of ovarian cancer and other FRα-expressing solid tumors. Based on the data from the ongoing clinical trials, Genmab intends to broaden the development plans for Rina-S within ovarian cancer and other FRα-expressing solid tumors. In January 2024, the U.S. Food and Drug Administration granted Fast Track designation to Rina-S for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer.

On September 15, 2024 Ipsen reported detailed final overall survival (OS) data from the Phase III CONTACT-02 trial investigating the combination of Cabometyx (cabozantinib) and atezolizumab in metastatic castration-resistant prostate cancer (mCRPC) (Press release, Ipsen, SEP 15, 2024, View Source [SID1234646611]). The trial investigated the combination regimen versus a second novel hormonal therapy (NHT) in men previously treated with one NHT and measurable soft-tissue disease. At a median follow-up of 24.0 months, these data demonstrated a numerical but not statistically significant improvement in OS for the combination versus a second NHT (hazard ratio: 0.89; 95% confidence interval: 0.72-1.10; P=0.296). As previously announced, the trial met the other primary endpoint of progression-free survival (PFS), demonstrating a statistically significant benefit in PFS.1 Safety for the combination appeared to be consistent with the known safety profiles of the individual medicines, and no new safety signals were identified.

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Based on the results of the final OS analysis and anticipated challenging regulatory environment in the countries in which Ipsen has commercialization rights (outside the US and Japan), Ipsen will not pursue regulatory submissions for this combination regimen in mCRPC.

We remain confident, in the proven profile of Cabometyx as a monotherapy and in combination with immunotherapy across approved indications, as well as its ongoing future potential.

Ipsen wishes to thank the patients, their families and healthcare teams for their participation in this clinical trial.

ENDS

About Cabometyx

Cabometyx (cabozantinib) is a small molecule that inhibits multiple receptor tyrosine kinases, including VEGFRs, MET, RET and the TAM family (TYRO3, MER, AXL).2 These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis (the growth of new blood vessels that tumors need to grow), drug resistance, modulation of immune activities and maintenance of the tumor microenvironment.2,3,4,5

Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of Cabometyx outside of the U.S. and Japan. Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited (Takeda) for the commercialization and further clinical development of Cabometyx for all future indications in Japan. Exelixis holds the exclusive rights to develop and commercialize Cabometyx in the U.S.

In over 65 countries outside of the United States and Japan, including in the European Union, Cabometyx is currently indicated as a:3

Monotherapy for advanced renal cell carcinoma (aRCC).
as first-line treatment of adults with intermediate- or poor-risk disease.
in adults following prior VEGFR-targeted therapy.
A combination with nivolumab for the first-line treatment of aRCC in adults.
Monotherapy for the treatment of adults living with locally advanced or metastatic differentiated thyroid carcinoma, refractory or not eligible to radioactive iodine who have progressed during or after prior systemic therapy.
Monotherapy for the treatment of hepatocellular carcinoma in adults who have previously been treated with sorafenib.
The detailed recommendations for the use of Cabometyx are described in the Summary of Product Characteristics (EU SmPC).

About mCRPC

Prostate cancer is the second most common cancer in men and the fourth most common cancer overall globally.6 In 2020, there were more than 1.4 million new cases of prostate cancer and about 375,300 deaths worldwide.6 Prostate cancer is considered mCRPC when it has spread beyond the prostate and does not respond to androgen-suppression therapies, a common treatment for prostate cancer.7 Men diagnosed with mCRPC often have a poor prognosis, with an estimated survival of 1-2 years.8

About CONTACT-02

CONTACT-02 is a global, multicenter, randomized, Phase III, open-label study that enrolled 575 patients who were randomized 1:1 to the experimental arm of Cabometyx in combination with atezolizumab and the control arm of a second NHT (either abiraterone and prednisone or enzalutamide). The study included patients with mCRPC who have measurable extra-pelvic soft tissue metastasis and who have progressed on one prior NHT. The two primary endpoints of the trial are progression-free survival (PFS) and OS. The PFS analysis was conducted in the first 400 randomized patients (PFS in the intent-to-treat [ITT] population) and assessed by a blinded independent radiology committee (BIRC) per RECIST 1.1. The OS analysis was conducted in the ITT population (n=507). The secondary endpoint is objective response rate (ORR) per BIRC. The trial is sponsored by Exelixis and co-funded by Ipsen, Roche and Takeda. Takeda is conducting the trial in Japan. More information about CONTACT-02 is available at ClinicalTrials.gov.