After a torrid time at recent conferences, Nektar Therapeutics looks like it will emerge from this year's Asco relatively unscathed. But updated results from the melanoma cohort of the company’s Pivot-02 trial of bempegaldesleukin are not much different from the results that fell flat at last year’s SITC congress.
True, 12-month follow-up from the phase II study, which tested bempegaldesleukin plus Bristol-Myers Squibb’s Opdivo in first-line disease, did find that four partial responders converted to complete remissions, which was hailed by Nektar and analysts alike as evidence of deepening response.
The data, presented on Saturday, were enough to send Nektar’s stock up 8% this morning. But, with no new remissions reported, the objective response rate remained at 53%, the same level seen at SITC 2018 after a median 7.2 months of follow-up (SITC 2018 – Nektar’s big reveal falls flat, November 11, 2018).
|Deepening response? Pivot-02 in 1st-line melanoma (NCT02983045)|
|Presentation||Data cut||Patients||Objective response rate||Complete response rate||ORR in PD-L1-neg|
|SITC 2017||Nov 2, 2017||11||7 (64%)||2 (18%)||3/5 (60%)|
|Asco 2018||May 29, 2018||28||14 (50%)||3 (11%)||5/11 (45%)|
|SITC 2018||Oct 1, 2018||38||20 (53%)||9 (24%)||6/14 (43%)|
|Asco 2019||Mar 29, 2019||38||20 (53%)||13 (34%)||6/14 (43%)|
|Source: Company presentations, Asco 2019 poster.|
Furthermore, only two of the complete responses came in PD-L1 negative patients, the same number as at the SITC update.
A better response in these patients might be needed to convince sceptics that bempegaldesleukin, previously known as NKTR-214, turns cold tumours hot – one of the key principles behind the project.
Indeed, in a cross-trial comparison, bempegaldesleukin does not look much better than checkpoint inhibitors alone on ORR, and fares worse when stacked up against Opdivo plus Yervoy.
The latest CR data with the Nektar project look favourable versus both PD-1 monotherapy and the Opdivo/Yervoy combo, suggesting that bempegaldesleukin/Opdivo is capable of putting patients into deeper remission. This, it might be surmised, could later translate into a survival benefit.
And the bempegaldesleukin/Opdivo combo looks less toxic than Opdivo/Yervoy, with around 10% of patients in Pivot-02 discontinuing owing to a treatment-related adverse event at 12 months; the discontinuation rate with Opdivo plus Yervoy is around 40%.
|Cross-trial comparison in 1st-line melanoma|
|Product||Follow-up (years)||Objective response rate||Complete response rate|
|Opdivo + Yervoy||4||58%||21%|
|Bempegaldesleukin + Opdivo||1||53%||34%|
|Source: Leerink note, May 30, 2019.|
Obviously these figures should be treated with the usual caution reserved for cross-trial analyses, and Nektar itself conceded that Pivot-02 was a single-arm trial; another factor making it difficult to interpret is the small number of patients involved.
The final judgement on bempegaldesleukin will not be possible until Nektar reports data from the pivotal programme, which comprises eight registrational studies in melanoma and renal, bladder and lung cancers, seeking to enrol over 3,500 patients in total. A phase III trial in melanoma is already recruiting, with progression-free survival data set to report in the second half of 2020, according to clinicaltrials.gov.
Disappointing updates at recent conferences mean that Nektar is well off the dizzy heights it hit in early 2018, when it signed a $1.8bn licensing deal with Bristol on the back of early data with bempegaldesleukin. Investors will be relieved that the picture has not worsened once again.
This story has been updated to clarify the timelines of the phase III trial.