Two-year JAVELIN Solid Tumor Data Phase 1 Final Results - Andrea Apolo

November 17, 2020

The anti-PD-L1 avelumab in urothelial carcinoma—A discussion with investigator Dr Andrea Apolo.

The JAVELIN Solid Tumor phase 1, open-label, dose-escalation trial investigated avelumab, a human monoclonal anti-PD-L1 antibody (anti-PD-L1), in patients with selected tumor indications (eg, NSCLC, breast cancer, colorectal cancer).  Pooled analysis of two JAVELIN cohorts that included patients with advanced or metastatic urothelial carcinoma (UC) who had progressed despite ≥1 course of platinum chemotherapy, or who were platinum ineligible (N=249) demonstrated—in those with  ≥6 months of follow-up (n=161)—an ORR of 17%. [Patel 2018; NCT01772004] These data led to the accelerated Federal Drug Administration (FDA) approval of avelumab in this setting. [Avelumab PI]

Now, 2-year data have been released, as well as results of exploratory posthoc analyses. In addition to still-impressive response rates and duration of response, a favorable association was found between early response and overall survival. [Apolo 2020; transcript] Other posthoc analyses involved subgroups defined by characteristics associated with a poor prognosis or high-risk disease, such as renal function (creatinine clearance <60 or ≥60 mL/min), ECOG PS, and the presence or absence of liver or visceral metastases. While exploratory results are not practice-changing, these data are exciting and likely to be of great value in validating prognostic factors in UC.

Other PD-L1 inhibitors approved in UC include pembrolizumab, atezolizumab, durvalumab, and nivolumab. The first targeted therapy for patients with advanced or metastatic UC that has progressed despite platinum chemotherapy, erdafitinib (for those with an FGFR3 or FGFR2 genetic alteration), received FDA approval in April 2019. Another targeted therapy, enfortumab vedotin-ejfv (a nectin-4–directed antibody and microtubule inhibitor conjugate), was approved in December 2019 for patients with advanced or metastatic UC after PD-1 or anti-PD-L1 immunotherapy and platinum chemotherapy.

Join Dr. Alicia Morgans, Associate Professor of Medicine and GU Medical Oncologist at Northwestern University, Chicago, Illinois, the USA in her conversation with Dr. Andrea Apolo, Investigator, National Cancer Institute Genitourinary Malignancies Branch; NIH Lasker Clinical Research Scholar; and Head, Bladder Cancer Section, Bethesda, Maryland, USA to find out more. Official study title: A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of Avelumab (MSB0010718C) in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications [NCT01772004]


Andrea B. Apolo, MD, Investigator Genitourinary Malignancies Branch NIH Lasker Clinical Research Scholar Head, Bladder Cancer Section, Center for Cancer Research National Cancer Institute, Bethesda, MD

Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.