How do you get a town the size of Slough into the clinic?

Data Insights

It’s no joke; few can deny the effect immuno-oncology has had on reshaping cancer treatment, and now evidence has emerged as to just how big the surge has been in patients enrolled into clinical studies of these medicines.

Currently enrolling combination trials involving anti-PD-(L)1 agents are seeking to recruit no fewer than 126,000 subjects – equivalent to the populations of Slough, UK, or Santa Clara, California – EP Vantage has found (see charts below). Cumulative totals suggest that this wave is now unstoppable, though what to make of the data generated is a different matter.

That last issue was tackled at the Sachs Forum on the sidelines of the recent Asco conference. The worrying message was that no clear-cut direction was likely from this combo effort until 2019, and many of the trial designs could confound the emerging data (Sachs Forum – Deciphering the immunology combo avalanche, June 2, 2017).

Not that this has stopped the avalanche: a report recently published by EP Vantage showed that the absolute number of anti-PD-(L)1 combo trials under way – with numerous mechanistic approaches – had surged nearly fourfold since November 2015 to reach 765 in April.

126,000 patients

A deeper dive reveals the number of subjects involved in this effort: at the April 13 cut of the dataset a grand total of 126,203 subjects were intended to be enrolled into 772 trials involving combinations of any of the industry’s MAbs against PD-1 or PD-L1.

The biggest single combo study is the monster Checkmate-227 trial of Bristol-Myers Squibb’s Opdivo combined with Yervoy and chemotherapy, aiming to enrol 2,220 lung cancer patients. 13 other combination trials in addition to Checkmate-227 have recruitment targets above 1,000, this analysis reveals.

And, while Keytruda leads the pack – just – in total combo studies initiated, it is the Bristol drug that is streets ahead in terms of patient enrolment, at over 45,000. The average recruitment target for an anti-PD-(L)1 combination trial is 163 subjects.

Anti-PD-(L)1 combination studies at April 13, 2017
Project Company Total subject enrolment No of trials
Opdivo Bristol-Myers Squibb 45,249 242
Keytruda Merck & Co 29,043 268
Tecentriq Roche 21,000 83
Imfinzi Astrazeneca 19,399 123
Others NA 11,512 56
Total 126,203 772*
Source: Clinicaltrials.gov; *includes 7 trials where PD-(L)1 agent is not specified.

Irrespective of study type Opdivo seems to be the most popular immuno-oncology drug, in terms of patient numbers, with nearly 80,000 subjects enrolled, the Moffitt Cancer Center’s Dr James Mulé told the Sachs Forum. As of March active studies of all immuno-oncology agents aimed to enrol a scarcely credible 250,363 patients, he said, up from 148,051 in December 2015.

Combo question

Of course, what the combo study data might be capable of showing is an entirely separate question given that few trials are powered specifically to show the effect of a combination head to head versus either of its components alone.

None of this seems to have bothered biopharma, which has gone on a tear in combinations since the start of 2014. Analysing the EP Vantage data by study starts shows how the number of patients in anti-PD-(L)1 combo trials under way surged from fewer than 20,000 at that point to breach the 120,000 mark in the middle of last year.

With every executive’s solution to a biotech’s failed asset seemingly lying in the answer “let’s combine it with an anti-PD-(L)1”, teasing out the precise additive benefit of combination therapies looks like becoming one of the biggest problems for investors over the coming years.

A full version of EP Vantage’s report can be downloaded here.

To contact the writers of this story email Jacob Plieth or Edwin Elmhirst in London at news@epvantage.com or follow @JacobPlieth or @EdwinElmhirst on Twitter

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