Astellas at ASCO 2024: Ahsan Arozullah in an Illuminating Dialogue Exchange with PharmaShots

Shots:

At ASCO 2024, Astellas Pharma presented 16 abstracts across several types of cancers with unmet medical needs

Today at PharmaShots, we have Ahsan Arozullah Sr. VP, Head of Oncology Development, shedding light on the advancement Astellas’ oncology portfolio for urothelial carcinoma, gastric cancer, and prostate cancer

Ahsan talks about the presented results from studies assessing combination of enfortumab vedotin with pembrolizumab, zolbetuximab and enzalutamide across indications

Saurabh: Astellas presented data on several oncology therapies at ASCO 2024. Can you tell us about the overall significance of these advancements for the treatment landscape of the specific cancers you addressed, such as urothelial carcinoma, gastric cancer, and prostate cancer? 

Ahsan: At this year’s ASCO, Astellas featured new data and post-hoc analyses of pivotal trials with 16 abstracts across several types of hard-to-treat cancers including prostate, urothelial, and gastric/gastroesophageal junction (GEJ) cancers.

The data at ASCO demonstrates the strength and breadth of Astellas’ growing oncology portfolio and provides new insights into our therapies for patients living with some of the most devastating cancers. The insights add to the growing body of evidence across Astellas’ clinical development programs and support our efforts to identify ways we can impact the course of the disease and redefine what is possible for patients who need it most.

People living with cancer, particularly those with advanced disease, have urgent unmet needs. This means that patients may have little to no treatment options for their cancer.

Our goal is to ensure people living with cancer can enjoy a longer and higher quality of life. We are dedicated to providing additional treatment options to physicians to help achieve this goal, to benefit as many people as possible as early as possible in the patient journey.

Saurabh: The data on enfortumab vedotin with pembrolizumab for advanced bladder cancer is very impressive. Can you elaborate on the significance of these findings and what differentiates this approach from existing therapies? 

Ahsan: The combination of enfortumab vedotin and pembrolizumab provides hope for patients with an urgent need for treatment options. These data further support the treatment combination as a new standard of care for locally advanced or metastatic urothelial cancer (la/mUC) patients, regardless of cisplatin eligibility.

Both enfortumab vedotin and pembrolizumab have independently shown a survival benefit in patients with la/mUC. The aim of combining these treatments is to enhance treatment and tumor response in eligible patients.

Non-clinical research has suggested that combining a vedotin antibody-drug conjugate (ADC) with a checkpoint inhibitor can result in a unique type of cell death and lead to a more augmented anti-tumor response than what is seen with each class of drug independently.

Phase 3 EV-302 clinical trial results showed enfortumab vedotin in combination with pembrolizumab nearly doubled median overall survival (OS) and significantly extended to progression-free survival (PFS) compared to platinum-containing chemotherapy in patients with previously untreated la/mUC.

Saurabh: With positive EV-302 results, what is the status of ongoing regulatory reviews by EMA, MHLW, and NMPA for enfortumab vedotin with pembrolizumab? 

Ahsan: Enfortumab vedotin is under review in several countries, including European Union countries, Japan and China. On July 26, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the approval of enfortumab vedotin with pembrolizumab in the European Union (EU). Data from the Phase 3 EV-302 trial evaluating enfortumab vedotin in combination with pembrolizumab versus chemotherapy in previously untreated la/mUC serve as the basis of ongoing regulatory reviews by the European Medicines Agency (EMA) and Japan’s Ministry of Health, Labour and Welfare (MHLW).

Saurabh: Can you discuss the final overall survival data from the SPOTLIGHT study on zolbetuximab for CLDN18.2 positive gastric/GEJ cancer? How do these findings strengthen the case for worldwide regulatory approvals? 

Ahsan: The final overall survival (OS) results from the SPOTLIGHT study found that zolbetuximab, a first-in-class claudin (CLDN) 18.2-targeted monoclonal antibody, continued to demonstrate statistically significant and clinically meaningful improvements in PFS and OS compared to placebo plus mFOLFOX6, with no new safety signals, in patients with HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma whose tumors are CLDN18.2 positive.

Specifically, median OS and PFS were significantly longer in zolbetuximab vs. placebo arms, consistent with the primary analysis. Separation of PFS and OS curves occurred earlier in the per-protocol population (PPS) analysis (excluding the majority of early withdrawals) compared with the intent-to-treat (ITT) population. Overall response rate (ORR) was similar between treatment arms in the ITT population and in patients with measurable lesions - despite this, time to progression (TTP) for patients with best overall response (BOR) of complete and partial responses (CR/PR) was numerically longer in the zolbetuximab vs. placebo arms.

Safety and tolerability were maintained from the primary analysis, with no new safety findings.

For patients with gastric cancer whose disease is locally advanced but inoperable or metastatic, to see a positive overall survival response in SPOTLIGHT is very encouraging given the limited treatment options available.

These data underpin the strength of the zolbetuximab clinical profile supporting the recent MHLW approval for zolbetuximab in Japan as well as other regulatory applications worldwide and reinforce its potential as a new first-line treatment option for this subset of patients with gastric and GEJ cancers.

Notably, on May 30, 2024, Astellas announced that the FDA has acknowledged the company's resubmission of the Biologics License Application (BLA) for zolbetuximab for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma whose tumors are CLDN18.2 positive. If approved, zolbetuximab would be the first CLDN18.2-targeted therapy approved in the U.S. for these patients.

On July 29, the CHMP of the EMA adopted a positive opinion recommending the approval of zolbetuximab in the EU. Additionally, EMA is expected to confirm publicly whether zolbetuximab's orphan designation will be maintained, upon receipt of EU marketing authorisation. CLDN18.2 testing helps define a population of patients with CLDN18.2-positive tumors who may benefit from targeted therapy with zolbetuximab in combination with chemotherapy.

An IHC assay—which is a standard diagnostic test used for cancer diagnosis and biomarker assessment—identifies CLDN18.2 positivity. IHC testing for CLDN18.2 positivity can be run alongside HER2 and other biomarker tests for patients with gastric cancer.

Saurabh: The EMBARK trial explored enzalutamide for nmHSPC/CSPC. Can you delve deeper into these post-hoc analyses on treatment suspension's impact on patient's quality of life and sexual health? 

Ahsan: In the EMBARK post hoc analysis presented at ASCO, the impact of treatment suspension on health-related quality of life (HRQoL) was explored and found that treatment suspension leads to clinically meaningful improvements in HRQoL.

In a separate patient-reported outcomes analysis of EMBARK, XTANDI (single agent) better preserved sexual activity in patients who were interested in sex or sexually active at baseline versus leuprolide alone. The addition of XTANDI to leuprolide had no impact on interest, activity, or satisfaction but may adversely affect erectile function, though differences were clinically non-significant.

These EMBARK analyses presented at ASCO help to improve understanding of the impact of prostate cancer treatment on HRQoL and provide insights that may help inform clinician treatment decision-making.

Saurabh: Does Astellas have any specific initiatives to address both affordability and patient access to these treatments, while also promoting diverse participation in your clinical trials?

Ahsan: Listening, Learning, and Collaborating are at the heart of how we partner with patient communities. By listening and learning from each other, we can drive better outcomes for patients. To this end, Astellas has programs in the U.S. to support access to our treatments through Astellas Pharma Support SolutionsSM including access and reimbursement support to help patients overcome challenges to accessing Astellas products, information regarding patient healthcare coverage options and financial assistance options that may be available to help patients with financial needs.

We are also committed to bringing underrepresented communities and demographics into more clinical trials. Consistent with commitment – and recognizing that increasing diversity in clinical trials is critical to improving health equity – Astellas supports the Pharmaceutical Research and Manufacturers of America’s (PhRMA) principles on enhancing diversity in clinical trial participation, part of the industry’s overarching Principles on Conduct of Clinical Trials and Communications of Clinical Trial Results. Our underlying goal is for our clinical trials to reflect the unique patient populations who may benefit from the medicines we develop. You can learn more about our clinical trials here: https://www.clinicaltrials.astellas.com/

Image Source: Canva

About the Author:

Ahsan Arozullah

Ahsan M. Arozullah, MD, MPH is a pharmaceutical executive with over 20 years of clinical research experience in pharmaceutical industry and academic settings. My passion to deliver lifesaving and life-changing therapies for patients is founded in my personal loss of loved ones to cancer. Cancer challenges all of us directly through the impact on people’s lives and their families and challenges us scientifically through the molecular and genetic modifications that hide cancers from our own immune systems. In my current position as Vice President of Medical Sciences-Oncology, I lead a global team of medical directors who provide world-class medical leadership to clinical development teams dedicated to creating the next generation of targeted oncology therapies. We collaborate with top scientists, clinicians, and caretakers from around the world to develop novel therapies and to study these therapies in patient-centric ways that facilitate our collective aim to bring the highest life changing value to patients.