S2302 Pragmatica-Lung: Activated!

The S2302 Pragmatica-Lung trial was activated on Monday, March 6. This is a phase III study with registrational intent, which tests a pembrolizumab plus ramucirumab combination against standard of care regimens (physician and patient choice) in patients with stage 4 or recurrent non-small cell lung cancer (NSCLC) that has previously been treated with immunotherapy and chemotherapy.

We have a bunch of eager beavers! Gundersen Lutheran Medical Center, in La Crosse, Wisconsin, and Lahey Hospital and Medical Center, in Burlington, Massachusetts, wasted no time this week, becoming the first sites to open the trial. Hats off to them for stunningly rapid activations! 

Breakneck speed isn’t required, but I do strongly encourage you to consider opening S2302 at your site soon. We know it’s an important trial, but here are 10 reasons why it’s also likely to be a remarkably easy trial to open, enroll to, and conduct.

Its data model is a masterpiece of concision
The trial has exactly two objectives (protocol p. 3), so sites collect only the data needed to 

1. answer the core question of whether patients live longer on the investigational treatment, and
2. maintain safety, in a setting where we are using drugs that have been tested before in many, many patients

Reduced AE reporting
See above! Safety profiles for these drugs are well established, so you’ll complete adverse event (AE) reports only for AEs that are serious, unexpected, and treatment-related.

EMR template
The NCI has provided an electronic medical record (EMR) template to help you quickly configure your EMR system for ordering drugs for this study (under “Protocol Related Documents” on the ctsu.org study page).

Simplified protocol and informed consent
The S2302 protocol is only 51 pages, and the simplified informed consent template is only 11. For comparison, in the two other SWOG registration studies now enrolling, the average protocol is 152 pages, and the average informed consent template is 19.

Bare-bones eligibility requirements
S2302 is enrolling adults with stage 4 or recurrent NSCLC, performance status of 0-2, and prior chemo and immunotherapy. The full set of criteria include a few other details, but they basically fit on a single page in the protocol. You can enroll the kinds of patients you see every day. Note you don’t have to say whether or not the patient was taking aspirin in 1978.

One-page treatment summary
In the master forms set, the treatment summary form is a single page: when did the patient start treatment, what did they receive, when did they stop, and why?

Zero-page baseline and follow-up tumor assessment forms
Yes, there are none.

Standard of care is physician and patient’s choice
Physicians with patients on the control arm can provide their standard treatment. There’s no list of options they have to choose among; they can treat just as they would in daily practice (in fact, that’s kind of the point).

No (fill in the blank) collection
There’s no need to collect trial-related: 

• blood draws,

• tissue specimens,

• lab values,

• imaging, 

• patient-reported outcomes, or

• concomitant medicines

Standard (not registration) audit schedule
S2302 is an FDA registration trial, but the pragmatic design means it will use the standard NCI audit schedule used for treatment trials.
 

From the ground up, this study was designed to be inclusive, across the full range of patients with this disease and sites that treat this disease. The eligibility criteria have been minimized, and participants will face very few additional demands beyond what they would face with standard treatment. By dramatically reducing the workload for sites and integrating trial processes as much as possible with standard practice, we’ve made it more feasible for small, community sites everywhere to open and enroll to the study.

The trial has garnered major attention for demonstrating that we in the NCI Clinical Trials Network (NCTN) can develop innovative, minimalist, pragmatic trials – even when there is FDA registrational intent – quickly and efficiently. We now need to demonstrate that we can follow through, opening, enrolling to, and meeting our accrual goals for the trial just as quickly and efficiently.

The sooner we reach this study’s enrollment goal of 700 patients, the greater the impact we’ll have, not just on patient care but also on how cancer trials are designed and conducted everywhere.

S1800A, this study’s phase II precursor, got off to an extraordinarily quick start, enrolling its first participant just 11 days after protocol activation. Can Pragmatica-Lung beat that time to first enrollment? If it does, I’ll let you know next week!