1stOncology™: Cancer Intelligence Service – Page 5755 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Update on US regulatory priority review of Lynparza in combination with abiraterone in metastatic castration-resistant prostate cancer

On December 15, 2022 AstraZeneca and MSD reported that the US Food and Drug Administration (FDA) has informed AstraZeneca that it will extend the Prescription Drug User Fee Act (PDUFA) date by three months to provide further time for a full review of the supplementary new drug application (sNDA) for Lynparza (olaparib) in combination with abiraterone and prednisone or prednisolone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) (Press release, AstraZeneca, DEC 15, 2022, View Source [SID1234625278]). The companies will continue to work with the FDA to facilitate the completion of the agency’s review.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

The sNDA is based on results from the pivotal PROpel Phase III trial, which were published in June 2022 in NEJM Evidence. In August 2022, the sNDA was granted Priority Review and AstraZeneca and MSD are committed to working with the FDA to bring this treatment option to patients with mCRPC.

In November, the European Medicines Agency’s Committee for Medicinal Products for Human Use adopted a positive opinion recommending approval of Lynparza in combination with abiraterone and prednisone or prednisolone in the EU for the treatment of adult patients with mCRPC for whom chemotherapy is not clinically indicated. This combination is also undergoing regulatory reviews in other countries.

Lynparza is approved in the US based on results from the PROfound Phase III trial as monotherapy for patients with homologous recombination repair (HRR) gene-mutated mCRPC (BRCA-mutated and other HRR gene mutations) who have progressed following prior treatment with enzalutamide or abiraterone; and in the EU, Japan, and China for patients with BRCA-mutated mCRPC who have progressed following prior therapy that included a new hormonal agent.

Notes

Metastatic castration-resistant prostate cancer
Metastatic prostate cancer is associated with a significant mortality rate.11 Development of prostate cancer is often driven by male sex hormones called androgens, including testosterone.12

In patients with mCRPC, their prostate cancer grows and spreads to other parts of the body despite the use of androgen-deprivation therapy to block the action of male sex hormones.6 Approximately 10-20% of men with advanced prostate cancer will develop castration-resistant prostate cancer (CRPC) within five years, and at least 84% of these men will have metastases at the time of CRPC diagnosis.6 Of patients with no metastases at CRPC diagnosis, 33% are likely to develop metastases within two years.5

Despite the advances in mCRPC treatment in the past decade with taxane and new hormonal agent (NHA) treatment, there is high unmet need in this population.6,8,9,13

PROpel
PROpel is a randomised, double-blind, multi-centre Phase III trial testing the efficacy, safety, and tolerability of Lynparza versus placebo when given in addition to abiraterone in men with mCRPC who had not received prior chemotherapy or NHAs in the mCRPC setting.

Men in both treatment groups also received either prednisone or prednisolone twice daily. The primary endpoint is investigator-assessed rPFS, with sensitivity analyses by BICR, and secondary endpoints include overall survival, time to secondary progression or death, time to first subsequent therapy, and quality of life measures.

In the PROpel Phase III trial, Lynparza is combined with abiraterone, an NHA which targets the androgen receptor (AR) pathway.

AR signalling engages a transcriptional programme that is critical for tumour cell growth and survival in prostate cancer.14,15 Preclinical models have identified interactions between PARP signalling and the AR pathway which support the observation of a combined anti-tumour effect of Lynparza and NHAs, like abiraterone, in both HRR deficient and HRR proficient prostate cancer.16-18

The PARP1 protein has been reported to be required for the transcriptional activity of androgen receptors; therefore, inhibiting PARP with Lynparza may impair the expression of androgen receptor target genes and enhance the activity of NHAs.14,17,19 Additionally, it is thought that abiraterone may alter/inhibit the transcription of some HRR genes which may induce HRR deficiency and increase sensitivity to PARP inhibition.16,18,20,21

For more information about the trial please visit ClinicalTrials.gov.

Lynparza
Lynparza (olaparib) is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumours harbouring a deficiency in HRR, such as those with mutations in BRCA1 and/or BRCA2, or those where deficiency is induced by other agents (such as NHAs).

Inhibition of PARP with Lynparza leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death.

Lynparza is currently approved in a number of countries across multiple tumour types including maintenance treatment of platinum-sensitive relapsed ovarian cancer and as both monotherapy and in combination with bevacizumab for the 1st-line maintenance treatment of BRCA-mutated (BRCAm) and homologous recombination repair deficient (HRD)-positive advanced ovarian cancer, respectively; for gBRCAm, HER2-negative metastatic breast cancer (in the EU and Japan this includes locally advanced breast cancer); for gBRCAm, HER2-negative high-risk early breast cancer (in Japan this includes all BRCAm HER2-negative high-risk early breast cancer); for gBRCAm metastatic pancreatic cancer; and HRR gene-mutated metastatic castration-resistant prostate cancer (BRCAm only in the EU and Japan). In China, Lynparza is approved for the treatment of BRCA-mutated metastatic castration-resistant prostate cancer as well as a 1st-line maintenance therapy in BRCA-mutated advanced ovarian cancer.

Lynparza, which is being jointly developed and commercialised by AstraZeneca and MSD, has been used to treat over 75,000 patients worldwide. Lynparza has a broad clinical trial development programme, and AstraZeneca and MSD are working together to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types. Lynparza is the foundation of AstraZeneca’s industry-leading portfolio of potential new medicines targeting DDR mechanisms in cancer cells.

Carina Biotech submits an Investigational New Drug (IND) application to the US FDA for LGR5-Targeted CAR-T Cell Therapy Candidate

On December 14, 2022 Carina Biotech files its first IND application for a CAR-T cell therapy targeting a solid cancer (Press release, Carina Biotech, DEC 15, 2022, View Source [SID1234625251]). The IND application is directed at a first-in-human Phase 1/2a clinical trial in advanced colorectal cancer patients.

has submitted an Investigational New Drug (IND) application to the US Food and Drug Administration (FDA) for first-in-human Phase 1/2a clinical trial of CNA3103, its LGR5-targeted chimeric antigen receptor T cell (CAR-T) therapy candidate, in patients with advanced colorectal cancer.

"We are delighted to achieve the major milestone of submitting this first IND to the FDA for our lead LGR5 CAR-T cell therapy candidate as our team continues to advance Carina’s vision to create a future that defeats cancer," said Deborah Rathjen, PhD, Carina’s Chief Executive Officer.

"Colorectal cancer is a lethal cancer, and a clear need exists for more effective treatment options. CAR-T cell therapy is a revolutionary and targeted cancer treatment option that harnesses a patient’s own immune system to fight their cancer. We are targeting the recruitment of the first patients in the Phase 1/2a trial in early 2023."

"Carina’s CAR-T cell therapy candidate, CNA3103, is targeted at LGR5, a cancer stem cell marker that is highly expressed on advanced colorectal cancer and some other cancers," stated José Iglesias, MD, Carina’s Chief Medical Officer. "In colorectal cancer patients, LGR5 expression has been correlated with a particularly poor prognosis and by targeting cancer stem
cells, this therapy may potentially reduce the tumor’s ability to generate new cancer cells, resulting in enhanced tumor suppression and preventing the relapses that are very common in patients with this disease."

Dr Iglesias added, "Colorectal cancer is the third most common cancer worldwide and the third most common cancer diagnosed in the United States, excluding skin cancers. Colorectal cancer is the deadliest cancer for young Australians and the second deadliest cancer for all Australians with its incidence rising in people under 50. Many younger people, who are often
diagnosed when their cancer is in its later stages, are given a very poor prognosis with very limited treatment options."

GC Wellbeing licenses out cancer cachexia treatment candidate to MThera Pharma

On December 14, 2022 GC Wellbeing reported the company has signed a technology transfer and joint development agreement for GCWB204, its cancer cachexia treatment candidate, with MThera Pharma.

In a European phase 2a clinical trial last year, GC Wellbeing confirmed the potential of GCWB204 as a treatment for cancer cachexia in multiple evaluation indicators related to the overall physical function of non-small cell lung cancer patients at eight weeks.

Although the company failed to secure statistical significance between groups regarding the stair climb power, the primary endpoint, it confirmed that the GCWB204-administered group had a statistically significant improvement in the quality of life (QoL) at eight weeks compared to the placebo group through a "Functional Assessment of Anorexia/Cachexia Treatment Trial Outcome Index" (FAACT-TOI) evaluation.

FAACT-TOI is a QoL questionnaire for non-small cell lung cancer patients.

Under the accord, GC Wellbeing will transfer the core technology of the fermentation method that can strengthen the special ginsenoside and research techniques such as the material of GCWB204, manufacturing method, and quality control.

MThera Pharma plans to devise a follow-up clinical trial with a new strategy by supplementing GCWB204’s material, manufacturing, and quality data.

However, the two companies did not disclose the investment amount, citing contractual reasons, but added they would jointly distribute royalties generated from the development of GCWB204.

"Through a strategic business agreement with MThera Pharma, which has extensive experience in manufacturing, quality control, and clinical development of natural medicines, the company will lay the groundwork for GCWB204 to enter the global market," a GC Wellbeing official said.

An MThera Pharma official also said, "The company concluded the contract after highly evaluating the marketability of GCWB204 for cancer patients and the possibility of a successful clinical trial."

The company plans to successfully conduct clinical trials in the U.S. and accelerate global expansion in the future, the MThera Pharma official added.

(Press release, GC Wellbeing, DEC 14, 2022, View Source [SID1234662182])

ImmuneOnco’s IMM2520 obtained approval of clinical research from the US FDA

On December 14, 2022, ImmuneOnco Biopharmaceuticals (Shanghai) Inc. (hereinafter referred to as "ImmuneOnco") reported that the newly-developed bispecific antibody-receptor recombinant protein drug (project number: IMM2520), targeting CD47 and PD-L1, obtained clinical research approval from the US FDA (Press release, ImmuneOnco Biopharma, DEC 14, 2022, View Source [SID1234655674]). This is the fourth IND approval for the company to date (others include IMM0306, IMM2902 and IMM40H), and it is another important milestone in the company’s development. Previously, IMM2520 was granted a Japanese patent and orther patents in China, the European union and the United States has been submitted. In November 2022, the IMM2520 has been approved by NMPA to carry out clinical trials. The approval by FDA for clincal trials strenthens the development of IMM2520 globally and consolidates the company’s leading position in the field of drug development for targeting CD47 and bispecific antibody research.

Dr. Tian, Wenzhi, Founder and Chairman of ImmuneOnco, said:

"We are very pleased that our IMM2520 program has received clinical trial research approval from the US FDA. IMM2520 is an antibody-receptor recombinant protein (mAb-Trap) that targets both CD47 and PD-L1. We believe that IMM2520 has great clinical development value, and we will actively promote clinical research and strive to bring it to market as soon as possible, so as to benefit the cancer patients."

IND Application of Biosyngen’s Cell Therapy (BRG01) for Nasopharyngeal Cancer Approved by China NMPA

On December 14, 2022, Guangzhou Biosyngen Co., Ltd. (hereinafter as "Biosyngen") reported on the approval granted by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for the company’s IND application for BRG01 Therapy (Press release, BioSyngen, DEC 14, 2022, View Source;c=View&a=index&aid=91 [SID1234631943]). BRG01 Therapy is an autologous T cell therapy for relapsed/metastatic nasopharyngeal cancer (NPC) treatment. The principle of autologous T cell therapy is to genetically modify patients’ own T cells to express additional receptors for Epstein-Barr virus (EBV) antigen recognition and T cell activation upon EBV+ tumor cell engagement.

"The IND approval of BRG01 Therapy marks a significant milestone for the company and in nasopharyngeal cancer treatment." said Joan Zhang, Chairman of Biosyngen. "As a biopharmaceutical company in immunotherapy, Biosyngen is committed to deliver more effective cancer therapy to address unmet needs for the benefit of cancer patients. Following this milestone, based on the company’s pipeline, Biosyngen has begun planning for multiple sponsor-initiated clinical trials which will lead to IND applications in China, the US and Singapore in the course of 2023. The indications targeted are hepatocellular cancer, colorectal cancer, gastric cancer, esophageal cancer and pancreatic cancer. Looking ahead, Biosyngen is assessing the marco environment in preparation for IPO within the next 18 months."

About BRG01

EBV is a human herpesvirus and has infected ~95% of population worldwide. It has been listed as Group 1 carcinogen ("Carcinogenic to humans") by World Health Organization (WHO) and proved to be associated with a range of diseases including nasopharyngeal cancer, EBV-positive gastric cancers, lymphoma and lymphoproliferative diseases. As one of the most common head and neck tumors, nasopharyngeal cancer, an epithelial carcinoma arising from the nasopharyngeal mucosal lining, is closely related to EBV infection. According to WHO, an estimated number of 133,000 new cases of nasopharyngeal cancer worldwide was reported in 2020; 50% of which was diagnosed in China. South China provinces such as Guangdong and Guangxi provinces make up for more than 60% of nasopharyngeal cancer patient population.

Though, existing practice such as immune checkpoint inhibitor has been applied in second-line and beyond treatment of nasopharyngeal cancer, overall response rates were mostly below 30%. In another words, more than 70% patients did not benefit from the existing therapy. Therefore, it is imperative to explore new approaches to improve efficacy and satisfy unmet medical needs.

BRG01 Therapy developed by Biosyngen is an engineered T cell therapy, also known as a type of adoptive immune cell therapy for nasopharyngeal cancer treatment. Patients’ T cells were isolated and genetically modified in a GMP-compliant facility to enhance their ability to recognize and attack specific antigens on cancer cells. The modified T cells are expanded ex vivo and infused back into the patient. The infused T cells would bind to the specific antigen on the cancer cells to mediate tumor killing. The preliminary safety and efficacy of BRG01 Therapy have been demonstrated in data from exploratory clinical trials.

The scientific direction of Biosyngen is focused on targeting multiple solid tumors and hematological tumors. The company has independently developed a number of exclusive technical platforms specifically for cancer immunotherapy, including IDENTIFIER, SUPER-T and MSE-T. These platforms greatly improved the company’s capability to overcome challenges in antigen identification, antibody TCR screening and identification of immune cell function.