The results of Roche’s Impower-150 trial made Tecentriq a first-line lung cancer contender, a position reinforced by yesterday’s partial success in Impower-131. The markets will continue to quibble about the relevance of some of the data, but the company is not done yet.
Next up is readout from three more phase III lung cancer studies with which the Swiss group will hope to secure its anti-PD-L1 MAb as a cornerstone of various chemotherapy regimens. An overlooked fact might be that Tecentriq actually has a chance to threaten the Merck & Co drug, even though Keytruda looks like it has the front-line setting sewn up.
|% market cap||6%|
|Event||Readout of Impower-130, 132 and 133 studies|
|*Based on percentage of forecast 2022 sales for all NSCLC use.|
Part of this stems from the fact that Impower-150 tested Tecentriq on top of Avastin, recognised as a first-line option for non-squamous NSCLC patients, whereas Merck has only shown Keytruda to beat chemo alone. Roche could claim that Keytruda has not cleared as high a bar as Tecentriq has, though Merck argues that Avastin is by no means established as a first-line treatment.
Meanwhile, in the first-line squamous NSCLC setting of Impower-131 Tecentriq could have an unhindered path to market unless broader analysis reveals a lack of clinical relevance, or if Merck’s similarly designed but smaller Keynote-407 trial reads out positive (Tecentriq’s chance to seize a poorly served lung cancer type, March 20, 2018).
The three relevant trials of Tecentriq that have yet to read out are Impower-130, 132 and 133. The last takes aim at another lung cancer setting where checkpoint inhibition has yet to make its mark – small-cell lung cancer (SCLC). SCLC patients have virtually no treatment options beyond cycles of platinum-based chemo.
45% of the market?
If Impower-131’s benefit holds up at full readout, and if 133 yields a positive result, by Roche’s estimation this would hand Tecentriq first-mover advantage in 45% of the total lung cancer market. It should be pointed out, however, that Keytruda's first-line NSCLC label in >50% PD-L1 expressers does include squamous patients.
Impower-130 and 132 test Tecentriq on top of the chemotherapies carboplatin and either Celgene’s Abraxane or Lilly’s Alimta in non-squamous NSCLC, and could consolidate the advantage that Tecentriq has already gained via Impower-150.
Roche’s aim in non-squamous disease is to make Tecentriq acceptable to as many doctors as possible, irrespective of their particular preference for the chemo used. Options include Celgene’s Abraxane, an albumin-bound paclitaxel formulation, and Lilly’s Alimta.
All these studies are event driven, like Impower-150, having overall and progression-free survival as co-primary endpoints, so it is impossible to be precise about when they will yield data or whether the two measures will read out together or sequentially. The Clinicaltrials.gov registry lists primary completion dates for them of between May 2018 and November 2019, but Roche said last month that all should generate data in the first half of 2018.
|Selected Tecentriq lung cancer studies|
|Study||Setting||Active treatment||Control||Trial ID||Date when fully recruited|
|Impower-150||1st-line non-squamous NSCLC||Tecentriq + carbo-tax +/- Avastin||Carbo-tax + Avastin||NCT02366143||Q4 2016 (reported positive; n=1,202)|
|Impower-131||1st-line squamous NSCLC||Tecentriq + carboplatin + tax/Abraxane||Carboplatin + Abraxane||NCT02367794||Q1 2017 (PFS positive; n=1,025)|
|Impower-130||1st-line non-squamous NSCLC||Tecentriq + carboplatin + Abraxane||Carboplatin + Abraxane||NCT02367781||Q1 2017 (n=6,505)|
|Impower-132||1st-line non-squamous NSCLC||Tecentriq + carbo-tax + Alimta||Carbo-tax + Alimta||NCT02657434||Q2 2017 (n=568)|
|Impower-133||1st-line SCLC||Tecentriq + carboplatin + etoposide||Carboplatin + etoposide||NCT02763579||Q2 2017 (n=400)|
|Source: Clinicaltrials.gov & company presentations.|
Surprisingly, Roche has still not filed Tecentriq for first-line lung cancer. The drug is approved in the second-line setting – increasingly irrelevant for anti-PD-(L)1 agents – but all Roche will say is that US and EU front-line submissions will be made this year.
It is possible that the company is awaiting data from some of the remaining Impower trials before filing. Meanwhile, Impower-150 data continue being picked apart to tease out the precise relevance of Tecentriq and Avastin in this setting, and investors are keenly awaiting mature survival data this year (All to play for in first-line lung cancer, Roche insists, February 2, 2018).
Either way, Roche has the largest number of phase III chemo-combo studies in first-line lung cancer, say Bernstein analysts.
If in this way the group wants to clip Keytruda’s wings, spare a thought for Bristol-Myers Squibb’s Opdivo, whose vanishing hopes in first-line NSCLC rest on an eleventh-hour analysis of the Checkmate-227 trial, based on subjects’ tumour mutation burden. Meanwhile, an earlier use – non-metastatic, stage III NSCLC – belongs to Astrazeneca’s Imfinzi, approved based on the Pacific study.
Keytruda and Imfinzi’s places in this important cancer are thus assured, and it seems that Roche is determined not to let Tecentriq become marginalised like Opdivo.