S2200: A Worthy Successor to PAPMET

In 2016, she was facing metastatic papillary renal cell carcinoma (RCC) and enrolled to the S1500 PAPMET trial. Randomized to cabozantinib, she was one of two patients on that study whose cancer disappeared entirely during treatment – a complete response.

PAPMET, of course, went on to establish cabozantinib (a tyrosine kinase inhibitor) as the standard of care for patients with metastatic papillary RCC (read all about it here).

PAPMET’s successor, PAPMET2 (aka S2200), was launched in September of 2022 (the same week Laura Esfeller joined SWOG, I believe). It builds on the success of PAPMET and of the KEYNOTE-427 trial, which demonstrated that immune checkpoint inhibitors can also have activity against papillary RCC.

The PAPMET2 hypothesis is that giving cabozantinib in combination with a checkpoint inhibitor will, by also activating the immune system, significantly extend progression-free survival (PFS) for these patients. The study randomizes them to either cabozantinib in combination with atezolizumab or cabozantinib alone, looking for a roughly 50 percent improvement in median PFS (to 13.5 months) on the combination arm.

The study is enrolling patients with metastatic papillary RCC, both type 1 and type 2, who have not previously had therapy for metastatic disease and who have a performance status of 0 – 2.

Benjamin L. Maughan, MD, PharmD, of the Huntsman Cancer Institute at the University of Utah, is study chair. City of Hope’s Sumanta “Monty” Pal, MD, (leader of the original PAPMET) is study co-chair. We also have study champions from ECOG-ACRIN – Yasser Ged, MBBS – and the Alliance – Arpita Desai, MD.

In September, the NCI and the Cancer Trials Support Unit (CTSU) convened a webinar on the three current NCTN clinical trials in renal cell carcinoma, which include Alliance trial A031801 and NRG study NRG-GU012. 

In his webinar presentation, PAPMET2 study chair Dr. Maughan noted that several single-arm – sometimes single-institution – trials have already demonstrated impressive objective response rates to such TKI–ICI combinations.

PAPMET2, however, is the first randomized trial of such a combination. We know both of these therapies are effective individually. This study will let us know, with high confidence, whether giving them in combination actually does help patients live longer without disease progression.

The trial’s enrollment goal is 200 patients. It’s been open for just over a year and has had something of a slow start, with enrollment at nine patients as of today, but it’s picking up steam and is now open at 129 sites, with roughly 200 additional sites in the process of opening the study. Thank you to all!

But given the rarity of this cancer, we will need support from many more centers to answer this question. Keep in mind that although PAPMET-the-first enrolled 152 patients overall, most centers that accrued patients enrolled only one or two. And more than 600 sites eventually opened the trial.

If your site has not yet activated S2200, I encourage you to visit the SWOG S2200 page or the CTSU S2200 page to learn more. VA medical centers are particularly welcome.

Note that the trial provides both cabozantinib and atezolizumab at no cost, so your patients may face a lower risk of financial toxicity than they would on non-trial treatment. They can learn more from our S2200 trial education materials.

With PAPMET, we changed practice and significantly improved outcomes for patients with this disease – patients like Laura Esfeller. With PAPMET2, we may be able to do it again!