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Nykode Therapeutics Initiates Phase 2 Trial of VB10.16 in Second Line HPV16-Positive Cervical Cancer

On April 19, 2024 Nykode Therapeutics ASA (OSE: NYKD), a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel immunotherapies, reported the initiation of the Phase 2 clinical trial VB-C-04 (Press release, Nykode Therapeutics, APR 19, 2024, View Source [SID1234642175]). The trial evaluates VB10.16, the company’s off-the-shelf therapeutic cancer vaccine candidate for HPV16-positive cancers, alone or in combination with Roche’s checkpoint inhibitor atezolizumab (Tecentriq1) in patients with HPV16-positive, PD-L1-positive, recurrent, or metastatic cervical cancer.

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Step 1 of VB-C-04 is a two-arm Phase 2 trial evaluating the efficacy and safety of VB10.16 alone or in combination with atezolizumab in patients with recurrent or metastatic cervical cancer refractory to firstline treatment with pembrolizumab plus chemotherapy +/-bevacizumab.

The Phase 2 trial (GOG-3091) will be conducted in the United States (U.S.) in collaboration with The GOG Foundation, Inc. (GOG Foundation)), a U.S. based not-for-profit organization with the purpose of promoting excellence in the quality and integrity in clinical trials in gynecologic malignancies. The GOG Foundation is the only clinical trialist group in the United States that focuses its research on patients with pelvic malignancies, such as cancer of the ovary (including surface peritoneal malignancies), uterus (including endometrium, soft tissue sarcoma, and gestational trophoblastic neoplasia), cervix, and vulva.

Dr. Bradley Monk, Director of GOG, said "Today marks an important step forward in our efforts to advance cancer treatment with the initiation of the Phase 2 trial of VB10.16 in second line HPV16-positive cervical cancer. This is a collaborative effort between GOG and Nykode, introducing a novel and promising approach to address a significant unmet medical need. As we embark on this Phase 2 trial, we are optimistic about the potential impact on reshaping the landscape of cancer care and look forward to contributing to advancements that can make a meaningful difference in patients’ lives."

"Initiating the VB10.16 trial for HPV16-positive cervical cancer addressing a high unmet medical need, is a significant step in our clinical development strategy," said Klaus Edvardsen, Chief Development Officer of Nykode Therapeutics. "The encouraging clinical profile and favorable tolerability exhibited by VB10.16 in combination with atezolizumab among patients with advanced HPV16 positive cervical cancer observed in VB-C-02 supports our dedication to advancing VB10.16 as an innovative immunotherapy for HPV16 positive cancers."

Atezolizumab is supplied by Roche. Nykode retains all commercial rights to VB10.16 worldwide.

About VB10.16

VB10.16 is a potentially first-in-class off-the-shelf therapeutic DNA-based cancer vaccine candidate in development for the treatment of human papillomavirus type 16 (HPV16)-positive cancers. The cancer vaccine is designed based on Nykode’s Vaccibody technology platform of targeting antigens to antigen presenting cells. VB10.16 has reported promising data from a Phase 2 trial in advanced PD-L1 positive cervical cancer patients (NCT04405349) in combination with atezolizumab with mOS not reached, but at least 24 months at the time of analysis. The vaccine-induced significant HPV16-specific T cell responses that were correlated with clinical responses. The candidate has also demonstrated favorable clinical data in a Phase 1/2a study in pre-cancerous HPV16-induced high grade cervical intraepithelial neoplasia (HSIL; CIN 2/3) demonstrating a statistically significant correlation of immune responses and clinical responses. Nykode is currently investigating VB10.16 in VB-C-03, an open-label, dose-finding Phase 1/2a trial evaluating VB10.16 in combination with MSD’s PD-1 inhibitor KEYTRUDA (pembrolizumab) in patients with HPV16-positive, PD-L1-positive, recurrent, or metastatic head and neck squamous cell carcinoma (HNSCC) in addition to the VB-C-04 trial initiated today.

About the Phase 2 Trial

The Phase 2 VB-C-04 trial (NCT06099418) is designed to evaluate the efficacy and safety of VB10.16. Step 1 is randomized and will evaluate VB10.16 as a monotherapy, and in combination with Roche’s checkpoint inhibitor atezolizumab as a second line treatment in patients with recurrent or metastatic cervical cancer. Step 1 of the trial is expected to enroll 60 patients with disease progression after combination treatment with pembrolizumab, chemotherapy +/-bevacizumab into the trial. Step 2 is intended to enroll additional patients in one cohort after reviewing the data from Step 1.

About Cervical Cancer

Cervical cancer is the fourth leading cause of cancer death in women worldwide and is most frequently diagnosed between the ages of 35 and 44. Each year around 600,000 women are diagnosed with cervical cancer worldwide. Almost all cases are caused by human papillomavirus (HPV) infection and HPV16 accounts for more than half of all cervical cancer cases. Approximately 80% of patients with cervical cancer have squamous cell carcinoma and most other patients have adenocarcinomas. Cervical cancer is often curable when detected early and effectively managed, but treatment options are more limited in advanced disease stages or when the cancer has spread.

Iovance Biotherapeutics Reports Inducement Grants under NASDAQ Listing Rule 5635(c)(4)

On April 19, 2024 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA) ("Iovance" or the "Company"), a biotechnology company focused on innovating, developing, and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) therapies for patients with cancer, reported that on April 18, 2024 (the "Date of Grant"), the Company approved the grant of inducement stock options covering an aggregate of 79,310 shares of Iovance’s common stock to thirty-seven new, non-executive employees (Press release, Iovance Biotherapeutics, APR 19, 2024, View Source [SID1234642173]).

The awards were granted under Iovance’s 2021 Inducement Plan, which was adopted on September 22, 2021 and amended on January 12, 2022, March 13, 2023, and February 26, 2024 and provides for the granting of equity awards to new employees of Iovance by the Company’s compensation committee in accordance with Nasdaq Listing Rule 5635(c)(4). Each of the stock options granted as referenced in this press release has an exercise price of $11.72, the closing price of Iovance’s common stock on the Date of Grant. Each stock option vests over a three-year period, with one-third of the shares vesting on the first anniversary of the employee’s start date (the "First Vesting Date"), and the remaining shares vesting in eight quarterly installments over the next two years, commencing with the first quarter following the First Vesting Date, subject to continued employment with the Company through the applicable vesting dates.

Alecensa Approved by FDA as the First Adjuvant Treatment for People with ALK-Positive Early-Stage Non-Small Cell Lung Cancer

On April 19, 2024 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that the U.S. Food and Drug Administration (FDA) has approved anaplastic lymphoma kinase (ALK) inhibitor Alecensa (generic name : alectinib) for adjuvant treatment following tumor resection for patients with-ALK positive non-small cell lung cancer (NSCLC) (tumors ≥ 4 cm or node positive) as detected by an FDA-approved test (Press release, Chugai, APR 19, 2024, View Source [SID1234642172]). Alecensa is now the only ALK inhibitor approved for people with ALK-positive early-stage NSCLC who have undergone surgery to remove their tumor. Outside the U.S., the medicine is currently under review for the indication by health authorities including in Europe, Japan, and Taiwan.

"We are very pleased that Alecensa, a Chugai originated medicine, is now approved by the FDA as the first adjuvant therapy for ALK-positive early-stage NSCLC. Alecensa has shown in a clinical trial to reduce the risk of death or recurrence by 76%. Bringing patients a new treatment option with the possibility of cure, may become a turning point in the treatment of ALK-positive early-stage NSCLC. We will work closely with Roche to deliver this treatment to patients awaiting all over the world, as soon as possible," said Chugai’s President and CEO, Dr. Osamu Okuda.

The approval is based on positive results from the Phase III ALINA study that demonstrated Alecensa reduced the risk of disease recurrence or death by 76% (hazard ratio [HR]=0.24, 95% CI: 0.13-0.43, p<0.001) compared with platinum-based chemotherapy in people with completely resected IB (tumor ≥ 4 cm) to IIIA (UICC/AJCC 7th edition) ALK-positive NSCLC.1 An exploratory analysis also showed improvement of central nervous system (CNS)-disease-free survival, reducing the risk of disease recurrence or death by 78% (HR=0.22; 95% CI: 0.08-0.58) compared with platinum-based chemotherapy.1 The safety and tolerability of Alecensa in this trial were generally consistent with previous trials in the metastatic setting and no unexpected safety findings were observed.1 These data were presented as a late-breaking oral at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 Presidential Symposium in October 2023 and were also recently published in the New England Journal of Medicine in April 2024.

Alecensa is a kinase inhibitor currently approved as first- and second -line treatment for ALK-positive metastatic NSCLC. It has demonstrated efficacy in patients, including those with CNS metastases, and now with this approval, these benefits could extend to people with early-stage NSCLC. Routine testing of resected surgical tissue or biopsy for ALK, EGFR and PD-L1 biomarkers in patients with stage IB to IIIA and select IIIB (UICC/AJCC 8th edition) NSCLC, in addition to in the advanced setting, is recommended by international guidelines, including the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines), to support clinicians’ decision-making. Approximately5% of people with NSCLC are ALK-positive, equating to approximately 90,000 people worldwide diagnosed each year.2,3,4

About the ALINA study
The ALINA study [NCT03456076] is a Phase III, randomized, active-controlled, multicenter, open-label study evaluating the efficacy and safety of adjuvant Alecensa (alectinib) compared with platinum-based chemotherapy in people with completely resected stage IB (tumor ≥4cm) to IIIA (UICC/AJCC 7th edition) anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). The study includes 257 patients who were randomly assigned to either the investigational or control treatment arm. The primary endpoint is disease-free survival (DFS). Secondary outcome measures include overall survival, central nervous system-DFS and percentage of patients with adverse events.

About Alecensa
Alecensa is a highly selective, central nervous system-active, oral medicine created at Chugai, a member of the Roche Group, Kamakura Research Laboratories for people with non-small cell lung cancer (NSCLC) whose tumors are identified as anaplastic lymphoma kinase (ALK) positive. Alecensa is already approved in over 100 countries as an initial (first-line) and second-line treatment for ALK-positive, metastatic NSCLC, including in the United States, Europe, Japan and China. In Japan, Alecensa has also been approved for the treatment of recurrent or refractory ALK fusion gene-positive anaplastic large cell lymphoma.

About lung cancer
Lung cancer is one of the leading causes of cancer death globally.5 Each year 1.8 million people die as a result of the disease; this translates into more than 4,900 deaths worldwide every day.5 In Japan, 127 thousand people are affected by this disease (2019).6 Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). NSCLC is the most prevalent type, accounting for around 85% of all cases.7 Today, about half of all people with early lung cancer (45-76%, depending on disease stage) still experience a cancer recurrence following surgery, despite adjuvant chemotherapy.8 Treating lung cancer early, before it has spread, may help prevent the disease from returning and provide people with the best opportunity for a cure.9

Trademarks used or mentioned in this release are protected by law.

Source:

Wu Y-L et al. Alectinib in Resected ALK-Positive Non–Small-Cell Lung Cancer. N Engl J Med 2024;390:1265-1276
Barlesi, et al. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT). Lancet 2016. 387(10026):1415-1426.
Tian, et al. Clinical characteristics and sequence complexity of anaplastic lymphoma kinase gene fusions in Chinese lung cancer patients. Lung Cancer 2017. 114:90-95.
Cancer.Net. Lung Cancer – Non-Small Cell: Statistics. [Internet; cited April 2024]. Available from: View Source
Thandra KC, et al. Epidemiology of lung cancer. Contemp Oncol. 2021;21(1):45-52.
Cancer Statistics, Cancer Information Service, National Cancer Center, Japan (National Cancer Registry) [Internet; cited 2024 April] Available from: View Source (Japanese Only)
American Cancer Society: What Is Lung Cancer? [Internet; cited 2024 April] Available from: View Source
Pignon JP et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26:3552-3559.
Hendricks LE et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO (Free ESMO Whitepaper) Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023;34(4): 339-357.

Pacylex Pharmaceuticals Announces First Patient Dosed in a Phase 2a Study of zelenirstat in Patients with Refractory Metastatic Colorectal Cancer

On April 18, 2024 Pacylex Pharmaceuticals Inc. (Pacylex) is a clinical-stage pharmaceutical company focused on the development of a new class of targeted therapies, N-myristoyltransferase inhibitors (NMTi) for the treatment of hematologic and solid tumor cancers, reported that the first patient has been dosed in a Phase 2a expansion study in patients with refractory metastatic colorectal cancer (Press release, Pacylex Pharmaceuticals, APR 18, 2024, View Source [SID1234645052]).

The Phase 1 dose escalation safety and tolerability study was conducted in 29 heavily pre-treated solid tumor and lymphoma patients who averaged 4 lines of prior drug therapy on which they relapsed or were refractory. Eight colorectal cancer patients were among those included in the study. The most common treatment related adverse events identified in the trial were mild to moderate gastrointestinal side effects which were self-limiting and occurred in a minority of patients. A recommended Phase 2 dose (RP2D) for expansion studies was established. Zelenirstat prolonged progression free and overall survival in Phase 1 solid tumor patients receiving the RP2D, compared to those receiving lower doses. Prolonged Stable Disease of 6 months or longer was observed in 57% (4/7) of the patients receiving RP2D, including a patient with metastatic colorectal cancer continuing on treatment for more than 1 year with reductions of approximately 50% in CEA (carcinoembryonic antigen) and tumor volumes.

"Given the patient benefits and excellent tolerability seen in our Phase 1 study, and particularly in our sentinel colorectal cancer patient, we are eager to see if other colorectal cancer patients receiving our Phase 2 dose will also benefit," said Dr. John Mackey, CMO of Pacylex. "People with refractory colorectal cancer desperately need new treatment options, and we are investigating whether zelenirstat can provide that."

"Adding colorectal cancer as our first solid tumor indication explores the broad potential for zelenirstat, a first-in-class oral cancer therapy, in both hematologic cancers and solid tumors," said Pacylex CEO Dr. Michael Weickert. "The importance of myristoylation to many cancer processes is underappreciated, and Pacylex is way ahead in developing this novel therapeutic class, NMT inhibitors, to treat cancer refractory to available treatments."

The Company has an ongoing Phase 2a study of patients with B-cell non-Hodgkin lymphoma. This colorectal cancer Phase 2a expansion study will enroll up to 20 subjects to assess the preliminary clinical activity and confirm the safety of zelenirstat in refractory colorectal cancer.

EditCo Bio, Inc. Unveils Novel Knockout CD4+ T-cell Pools to Transform Cancer and Autoimmune Research

On April 18, 2024 EditCo Bio, Inc., a pioneer at the forefront of genome engineering innovation, reported the launch of its Knockout CD4+ T-cell Pools (Press release, EditCo Bio, APR 18, 2024, View Source [SID1234642167]). This latest addition to EditCo Bio’s product lineup marks a significant leap forward in CRISPR-mediated gene editing, providing the scientific community with an advanced tool for primary T-cell editing that surpasses the capabilities of traditional methodologies.

With the advent of CRISPR-Cas9 technology, genetic engineering has entered a new era of precision, particularly in the realm of primary immune cell editing. T-cells, pivotal in the immune response, hold immense promise for elucidating the pathways of various diseases, including cancer and autoimmune conditions. Yet, conventional T-cell editing techniques have often fallen short, plagued by scalability issues and inconsistent outcomes.

Leveraging the power of EditCo Bio’s cutting-edge, automated platform, researchers can now bypass the challenging optimization steps and access highly functional edited T-cells ready for immediate use. This innovation not only accelerates the journey from research discovery to clinical application but also delivers several key benefits:

Rapid Results: A novel 7-day protocol harnesses EditCo Bio’s unique multi-guide technology to achieve knockout efficiencies beyond 90% in primary human CD4+ T-cells.
Dependable Performance: Post-editing, CD4+ cell pools maintain over 80% viability before cryopreservation and can expand 40-fold over 14 days, regardless of TCR stimulation.
Optimal Functionality: After cryo-recovery, these CD4+ T-cell pools exhibit remarkable functional integrity, matching control cells in IL2, IFNG, and TNFA protein production post-PMA/ionomycin stimulation. Further, cultured cells retain over 90% viability and maintain editing efficiency for at least 14 days.
"For too long, the potential of primary T-cell editing has been constrained by the technical limitations of existing methods," said Travis Maures, CSO of EditCo Bio. "With the launch of our Knockout CD4+ T-cell Pools, EditCo Bio is breaking down these barriers, offering researchers the precision, efficiency, and scalability needed to advance the frontiers of immunotherapy and cellular research while allowing them the benefit of bypassing tedious protocol optimization. This innovation is a testament to our commitment to empowering scientists worldwide, driving forward the possibilities of gene editing to address some of the most pressing challenges in research today."

The introduction of Knockout CD4+ T-cell Pools is a strategic extension of EditCo Bio’s comprehensive Engineered Cell portfolio. It further solidifies the company’s position as a leader in cell engineering solutions that includes knockout and knock-in technologies for immortalized cells and iPSCs. EditCo Bio plans to expand the range of its edited primary cells products beyond CD4+ T-cells into other primary cell subsets that will be commercially available to researchers worldwide later this year.

For more information regarding EditCo Bio’s CD4+ T-cell Pools, visit www.EditCo.bio/contact.