During the upcoming annual meeting of the European Society for Medical Oncology (ESMO), being held in Barcelona, September 13-17, 2024, expect presentations to include new data on advances in the treatment of hard-to-treat cancers using approved and investigational agents, including enfortumab vedotin (Padcev™; Astellas/Pfizer/Seagen), Zolbetuximab (previously known as IMAB362), Enzalutamide (Xtandi®; Astellas/Pfizer) and various pipeline products.
During the ESMO meeting, Astellas Pharma will present eight abstracts across a broad range of cancer types, including prostate, urothelial, gastric, and gastroesophageal junction (GEJ), and pancreatic cancers. The presented data is expected to reinforce the company’s commitment to making a meaningful difference to people living with advanced and hard-to-treat cancers. In addition, two abstracts will feature Phase 1 data presented for the first time from immuno-oncology and targeted protein degradation assets.
The data presented includes:
- Enfortumab vedotin, an Antibody-drug Conjugate (ADC) which is being evaluated in combination with pembrolizumab (Keytruda®; Merck & Co/Merck Sharp & Dohme/MSD) in patients with previously untreated metastatic urothelial cancer, a disease iwith limited treatment options for patients ineligible for cisplatin-based chemotherapy have historically been limited.[1]
- Zolbetuximab, an antibody targeting claudin-18 isoform 2 (CLDN18.2), has shown efficacy in the treatment of patients with CLDN18.2-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (mG/GEJ) and metastatic pancreatic cancer. The investigational agent is evaluated in the SPOTLIGHT trial, which investigated the efficacy and safety of first-line zolbetuximab plus mFOLFOX6 (modified folinic acid [or levofolinate], fluorouracil, and oxaliplatin regimen) versus placebo plus mFOLFOX6. The outcome of the syudy suggest that zolbetuximab in combination with mFOLFOX6 may possibly represent a new first-line treatment in patients diagnosed with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma.
- Enzalutamide, a second-generation androgen receptor inhibitor indicated for the treatment of metastatic disease as well as in the treatment of non-metastatic castration resistant prostate cancer (nmCSPC) and which is evaluated in high-risk biochemical recurrent non-metastatic hormone-sensitive prostate cancer treated with enzalutamide in the primary or salvage settings. Earlier studies suggest that ennzalutamide has considerable potential as a therapeutic strategy for nmCSPC, either used alone or in combination with androgen deprivation therapy (ADT) in the primary or in the salvage settings, concluding while additional trials will be required to further understand the efficacy and side-effect profile of enzalutamide monotherapy, the use of enzalutamide instead of ADT is an appealing strategy. [2]
“The data presented at ESMO are an exciting demonstration of the strength of our portfolio and the transformative potential of our pipeline to help deliver outcomes that matter for patients,” Tadaaki Taniguchi, MD, PhD, Chief Medical Officer of Astellas.
“We have made a long-term commitment to helping people living with hard-to-treat cancers by both investing in next-generation modalities like targeted protein degradation and immuno-oncology, and by maximizing the number of patients that could benefit from our approved medicines,” Taniguchi added.
Highlights presented at the 2024 ESMO Congress include:
- Data from the Phase 3 EV-302 study, evaluating Nectin-4 expression and response to first-line treatment of enfortumab vedotin in combination with pembrolizumab in previously untreated locally advanced or metastatic urothelial cancer (la/mUC). These results support the combination as a first-line advancement across la/mUC patient subgroups, regardless of Nectin-4 expression. Results published earlier this year suggest a survival benefit from enfortumab vedotin in combination with pembrolizumab versus chemotherapy in metastatic urothelial carcinoma, outperforming standard chemotherapy and marking a pivotal leap inn the management of the disease [3][4]
- Five-year follow-up data from the Phase 1/2b EV-103 DE/A study, analyzing durable responses and meaningful survival to enfortumab vedotin in combination with pembrolizumab in patients with first-line cis-ineligible la/mUC. These results further support the broad suitability, regardless of cis-eligibility, and long-term benefits of this regimen in la/mUC.
- Final pooled overall survival data from the Phase 3 SPOTLIGHT and GLOW trials, evaluating zolbetuximab plus chemotherapy as a first-line treatment in patients with HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma whose tumors are Claudin 18.2-positive. [5]
- Updates involving a Phase 2 trial in progress assessing zolbetuximab in combination with gemcitabine and nab-paclitaxel (GN) versus GN monotherapy as first-line treatment of Claudin 18.2-positive metastatic pancreatic cancer.
- Phase 3 EMBARK post-hoc analyses, evaluating enzalutamide (Xtandi®; Astellas/Pfizer) in combination with leuprolide and as monotherapy versus leuprolide alone in patients with high-risk biochemical recurrent non-metastatic hormone-sensitive prostate cancer. These results support the benefits of enzalutamide both in combination with leuprolide and as monotherapy in patients aged <70 and ≥70 years.
Clinical data from lead pipeline assets
- Phase 1 data from ASP3082, the first protein degrader targeting KRAS G12D mutant to enter clinical trials, in patients with advanced pancreatic, colorectal, and non-small cell lung cancer; and preclinical, translational/early clinical data from ASP1570, a novel DGKζ inhibitor, in patients with advanced solid tumors. The results support continued study of these investigational therapies for the treatment of various cancer types.
Presentations at 2024 ESMO Congress include
Enfortumab vedotin
| Presentation title | Speaker | Presentation details |
| EV-302: Exploratory Analysis of Nectin-4 Expression and Response to 1L Enfortumab Vedotin (EV) + Pembrolizumab (P) in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer (la/mUC) | T. Powles | Type: Mini Oral Session Abstract Number: 1966MO Date: September 15 |
| Study EV-103 Dose Escalation/Cohort A (DE/A): 5y Follow-Up Of First-Line (1L) Enfortumab Vedotin (EV) + Pembrolizumab (P) in Cisplatin (cis)-Ineligible Locally Advanced Or Metastatic Urothelial Carcinoma (la/mUC) | J. Rosenberg | Type: Poster Abstract Number: 1968P Date: September 15 |
| Epidemiology and treatment patterns of patients with locally advanced or metastatic urothelial cancer in France: a non-interventional database study | F. Joly | Type: Poster Abstract Number: 2001P Date: September 15 |
Zolbetuximab
| Presentation title | Speaker | Presentation details |
| First-line (1L) zolbetuximab + chemotherapy in patients (pts) with claudin 18.2 (CLDN18.2) +, HER2–, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: A pooled final analysis of SPOTLIGHT + GLOW | Y-K Kang | Type: Poster Abstract Number:1438P Date:September 16 |
| Zolbetuximab With Gemcitabine + Nab-Paclitaxel (GN) in First-Line Treatment of Claudin 18.2–Positive Metastatic Pancreatic Cancer (mPC): Phase 2, Open-Label, Randomized Study | W. Park | Type: Poster Abstract Number:1532TiP Date:September 16 |
Enzalutamide
| Presentation title | Speaker | Presentation details |
| Enzalutamide (enza) with or without leuprolide in patients (pts) with high-risk biochemically recurrent (hrBCR) prostate cancer (PC): EMBARK post-hoc analysis by age. | N. D. Shore | Type: Poster Abstract Number: 1638P Date: September 15 |
Pipeline agents
| Presentation title | Speaker | Presentation details |
| Phase 1/2 Trial of ASP1570, a Novel Diacylglycerol Kinase ζ Inhibitor, in Patients With Advanced Solid Tumors. | D. Olsen | Type: Poster Abstract Number: 1004P Date: September 14 |
| Preliminary safety and clinical activity of ASP3082, a first-in-class, KRAS G12D selective protein degrader in adults with advanced pancreatic (PC), colorectal (CRC), and non-small cell lung cancer (NSCLC) | W. Park | Type: Proffered Paper Session Abstract Number: 608O Date: September 15 |
Clinical trials
A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer (EV-103) – ClinicalTrials.gov ID NCT03288545
Safety and Efficacy Study of Enzalutamide Plus Leuprolide in Patients With Nonmetastatic Prostate Cancer (EMBARK) – ClinicalTrials.gov ID NCT02319837
A Study of Zolbetuximab (IMAB362) Plus CAPOX Compared With Placebo Plus CAPOX as First-line Treatment of Subjects With Claudin (CLDN) 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (GLOW) – ClinicalTrials.gov ID NCT03653507
A Study of Zolbetuximab (IMAB362) in Adults With Pancreatic Cancer – ClinicalTrials.gov ID NCT03816163
A Phase 3 Efficacy, Safety and Tolerability Study of Zolbetuximab (Experimental Drug) Plus mFOLFOX6 Chemotherapy Compared to Placebo Plus mFOLFOX6 as Treatment for Gastric and Gastroesophageal Junction (GEJ) Cancer (Spotlight) – ClinicalTrials.gov ID NCT03504397
Highlights of prescribing information
Enfortumab vedotin (Padcev™; Astellas/Pfizer/Seagen) [Prescribing Information]
Enzalutamide (Xtandi®; Astellas/Pfizer) [Prescribing Information]
References
[1] Zhu X, Koshkin VS. Enfortumab vedotin and pembrolizumab as new first-line standard for metastatic urothelial cancer. Med. 2024 Feb 9;5(2):106-108. doi: 10.1016/j.medj.2023.11.010. Epub 2023 Dec 20. PMID: 38128535.
[2] Shelan M, Achard V, Appiagyei F, Mose L, Zilli T, Fankhauser CD, Zamboglou C, Mohamad O, Aebersold DM, Cathomas R. Role of enzalutamide in primary and recurrent non-metastatic hormone sensitive prostate cancer: a systematic review of prospective clinical trials. Prostate Cancer Prostatic Dis. 2024 Sep;27(3):422-431. doi: 10.1038/s41391-024-00829-9. Epub 2024 Apr 8. PMID: 38589645; PMCID: PMC11319196.
[3] Benjamin DJ, Rezazadeh Kalebasty A, Prasad V. The Overall Survival Benefit in EV-302: Is Enfortumab Vedotin plus Pembrolizumab the New Frontline Standard of Care for Metastatic Urothelial Carcinoma? Eur Urol Oncol. 2024 Jun;7(3):313-315. doi: 10.1016/j.euo.2024.02.010. Epub 2024 Mar 13. PMID: 38485615.
[4] Bellmunt J, Nadal R. Enfortumab vedotin and pembrolizumab combination as a relevant game changer in urothelial carcinoma: What is left behind? Med. 2024 Jun 14;5(6):490-492. doi: 10.1016/j.medj.2024.04.006. PMID: 38878766.
[5] Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, Van Cutsem E, Xu RH, Aprile G, Xu J, Chao J, Pazo-Cid R, Kang YK, Yang J, Moran D, Bhattacharya P, Arozullah A, Park JW, Oh M, Ajani JA. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023 May 20;401(10389):1655-1668. doi: 10.1016/S0140-6736(23)00620-7. Epub 2023 Apr 15.
Featured image: © 2016 – 2024 Sunvalley Communication. Used with permission. This Article was first published on September 11, 2024 in ADC Review | Journal of Antibody-drug Conjugates.
DOI 10.14229/jadc.2024.09.12.001
, being held in Barcelona, September 13-17, 2024, expect presentations to include new data on advances in the treatment of hard-to-treat cancers using approved and investigational agents, including enfortumab vedotin (Padcev™; Astellas/Pfizer/Seagen), Zolbetuximab (previously known as IMAB362), Enzalutamide (Xtandi®; Astellas/Pfizer) and various pipeline products.){kind=link}