Avid Bioservices Inc (CDMO)

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The first look-in was scheduled at 33% eventing to guard the safety and integrity of the trial, and with good reason. We know there have been previous issues like unusually high control arm results, problematic randomizing, right up to clear sabotage: the outright dose switching interference in the preceding Phase2 trial.

At 33% the IDMC advised that the Doce control arm had outperformed to such an extent that it came to within the two months of the planned separation with the Bavi arm. That was a RED FLAG for Peregrine, as it should be! It sounds like the Doce arm which should have been around 9.9 months went beyond 12 months.

Without unblinding the trial, the company would have been taking too big of a risk in terms of time and money. PPHM needed to investigate. A “dramatic” record setting Doce arm in this ECOG group in advanced 2nd line NSCLC is a major RED FLAG.

The company reported that the Bavi arm performed as was expected. That’s good, but they needed to know why the control arm was super high, and impinging on the minimum separation margin. You don’t responsibly let that ride.

A Doce comparator arm with standard deviation plus a margin applied should have allowed at least a two month separation between the two arms, per design, at 33% eventing.

Again the designed minimum separation margin was violated. RED FLAGS!

My contention was that further data from the trial should normalize and bring the Doce arm data back within its historical standard deviation. A larger data base should always give a more naturalistic (falling within standard deviation) account and smoother data. That is why Phase3 trials are generally so large.

But, if whatever factor was driving the Doce anomaly continued, even with further data, and Peregrine ignored it, that would be a real problem. Peregrine acted responsibly.

Peregrine needs to learn what is, or was, driving the the early control arm to perform beyond any historical records.

Something abnormal was happening with the control arm. Peregrine needed to investigate.

Bavi performed as per trial design. BAVI WORKS!

The Doce arm was way out of line. RED FLAG!

Bavi works, and PPHM will continue developing and expanding I-O combination trials with our AZN, MSK and NCCN collaborators.

IMO

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