At a glance: The JAVELIN lung cancer trials

Author: Hannah Kitt

The PD-L1 inhibitor avelumab (formerly MSB0010718C) is being evaluated in the JAVELIN clinical trials as a single agent or in combination with an assortment of anticancer agents for the treatment of various malignancies.

Here is a quick guide to the nine JAVELIN trials investigating avelumab in patients with non-small-cell lung cancer (NSCLC), two of which also include patients with SCLC or mesothelioma. For trials that include multiple solid tumor types, only the top-line results for the NSCLC, SCLC, and mesothelioma cohorts are given.

We will update the page as new results become available.

JAVELIN Solid Tumor: Published

Phase 1
Patient population: Locally advanced or metastatic solid tumors	Treatment: Avelumab 1, 3, 10, or 20 mg/kg every 2 weeks	Sponsor: EMD Serono
https://clinicaltrials.gov/ct2/show/NCT01772004

The initial dose-escalation phase of the trial, first reported in The Lancet Oncology in 2017, showed the 10 mg/kg dose of avelumab to have a manageable safety profile and acceptable antitumor activity to be chosen for further clinical trials.

Results from one of the NSCLC expansion cohorts were also reported in The Lancet Oncology in the same year, and showed an objective response rate (ORR) with avelumab of 12% and a disease control rate (DCR) of 50% among the participants, all of whom had received one previous line of platinum-based chemotherapy for stage IIIB or IV disease.

Avelumab also showed antitumor activity and tolerable safety in the cohort of patients with treatment-naïve metastatic or recurrent NSCLC. As published in the Journal for ImmunoTherapy of Cancer in 2020, the ORR was 19.9%, median progression-free survival (PFS) was 4.0 months, and median overall survival (OS) was 14.1 months.

The agent was also active in previously treated patients with malignant mesothelioma, with an ORR of 9%, DCR of 58%, median PFS of 4.1 months, and median OS of 10.7 months. The data from this cohort were reported in JAMA Oncology in 2019.

JAVELIN Lung 200: Published

Phase 1
Patient population: Stage IIIB or IV NSCLC that progressed after platinum-based doublet therapy	Treatments: Avelumab 10 mg/kg every 2 weeks; docetaxel 75 mg/m2 every 3 weeks	Sponsor: EMD Serono Research & Development Institute, Inc
https://clinicaltrials.gov/ct2/show/NCT02395172

The primary analysis, published in The Lancet Oncology in 2018, showed that avelumab treatment did not significantly prolong the primary endpoint of OS relative to docetaxel in PD-L1 positive (≥1%) NSCLC patients. However, a prespecified exploratory analysis revealed that patients with high PD-L1 expression may derive a greater OS benefit with avelumab than docetaxel.

And indeed, results from the 2-year follow-up – reported in the Journal of Thoracic Oncology in 2021 – showed that the 2-year OS rates were nearly doubled with avelumab versus docetaxel among patients with a PD-L1 expression level of at least 50% (36.4 vs 17.7%) or at least 80% (40.2 vs 20.3%).

A post-hoc analysis published in Lung Cancer in 2021 revealed that the primary OS analysis may have been confounded by subsequent immune checkpoint inhibitor use in a larger proportion of patients in the docetaxel than avelumab arm (26 vs 4%).

JAVELIN Lung 101: Ongoing

Phase 1b/2
Patient population: Locally advanced or metastatic NSCLC	Treatments: Avelumab 5 or 10 mg/kg once every 2 weeks plus either crizotinib 200 or 250 mg once or twice a day or lorlatinib 50, 75, or 100 mg once a day	Sponsor: Pfizer
https://clinicaltrials.gov/ct2/show/NCT02584634

Initial results from the phase 1b part of the study, reported at the 2018 ASCO Annual Meeting, showed that avelumab plus lorlatinib has a manageable safety profile and promising efficacy among ALK-positive NSCLC patients previously treated with any number of ALK inhibitors.

By contrast, the avelumab–crizotinib combination was not well tolerated by patients with ALK-negative NSCLC who had received at least one prior systemic therapy, with dose-limiting toxicities occurring in 41.7%.

JAVELIN Lung 100: Ongoing

Phase 3
Patient population: Treatment-naïve recurrent or metastatic PD-L1-positive NSCLC	Treatments: Avelumab 10 mg/kg every 2 weeks or weekly for 12 weeks and then every 2 weeks; investigators choice of five platinum-based doublet therapies	Sponsor: EMD Serono Research & Development Institute, Inc
https://clinicaltrials.gov/ct2/show/NCT02576574

This multicenter study is comparing the efficacy and safety of avelumab monotherapy with platinum-based doublet chemotherapies for the first-line treatment of advanced NSCLC. The co-primary endpoints of the study are PFS and OS in patients with high tumoral levels of PD-L1.

JAVELIN Medley VEGF: Ongoing

Phase 2
Patient population: Locally advanced or metastatic NSCLC or urothelial cancer	Treatment: Avelumab 800 mg every 2 weeks plus axitinib 5 mg twice a day	Sponsor: Pfizer
https://clinicaltrials.gov/ct2/show/NCT03472560

Results presented in a poster at The Society for Immunotherapy of Cancer’s 2020 annual meeting showed a confirmed ORR of 31.7% in the NSCLC cohort, which comprised individuals with no activating EGFR, ALK, or ROS1 alterations who had received at least one prior platinum-containing therapy but no more than two prior lines of systemic therapy. The median PFS was 5.5 months and the combination had a manageable safety profile, which was consistent with the individual drug profiles.

JAVELIN PARP Medley: Ongoing

Phase 1b/2
Patient population: Locally advanced or metastatic solid tumors	Treatment: Avelumab plus talazoparib at various dose levels	Sponsor: Pfizer
https://clinicaltrials.gov/ct2/show/NCT03330405

This trial is investigating the antitumor activity and safety of avelumab in combination with the PARP inhibitor talazoparib in patients with locally advanced or metastatic solid tumors, including NSCLC.

JAVELIN Chemotherapy Medley: Ongoing

Phase 1b/2
Patient population: Treatment-naïve locally advanced or metastatic solid tumors	Treatments: Avelumab 800 or 1200 mg every 3 weeks in combination with chemotherapy doublets	Sponsor: Pfizer
https://clinicaltrials.gov/ct2/show/NCT03317496

This study, investigating avelumab in combination with chemotherapy as a first-line treatment in patients with locally advanced or metastatic solid tumors, includes patients with nonsquamous NSCLC and those with cisplatin-eligible urothelial cancer. The PD-L1 inhibitor may be combined with other anticancer agents in these and other tumor types as the trial progresses.

JAVELIN Medley: Recruiting

Phase 1b/2
Patient population: Locally advanced or metastatic solid tumors	Treatments: Avelumab plus utomilumab, PF-04518600, PD-0360324, or CMP-001; avelumab plus utomilumab and PF-04518600 or CMP-001; avelumab plus CMP-001 and PF-04518600	Sponsor: Pfizer
https://clinicaltrials.gov/ct2/show/NCT02554812

The investigators are assessing the efficacy and safety of the PD-L1 inhibitor in combination with other cancer immunotherapies in patients with locally advanced or metastatic solid tumors including NSCLC and SCLC.

JAVELIN IL-12: Discontinued

Phase 1b
Patient population: Locally advanced, unresectable, or metastatic solid tumors	Treatment: Avelumab plus M9241 at various doses	Sponsor: EMD Serono Research & Development Institute, Inc
https://clinicaltrials.gov/ct2/show/NCT02994953

This study was discontinued in October 2020 due to a lack of efficacy in the urothelial cancer dose-expansion cohort, despite prolonged clinical responses in the dose-escalation phase presented at the ESMO Congress 2019 in a poster session.

This independent article was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany