The year-end oncology congress season is upon us, and the first instalment for biopharma investors starts on September 8 with the IASLC World Conference on Lung Cancer, albeit still in virtual format.
The meeting’s oral sessions look to be focused on the front-line NSCLC setting for follow-on anti-PD-(L)1 MAbs, with a notable presence from Chinese companies aiming to challenge Keytruda. While a targeted NSCLC session will unveil Abbvie/Seagen’s low-key asset telisotuzumab vedotin, perhaps the biggest spotlight will fall on Astrazeneca’s separate Poseidon study, which raised tremelimumab from the dead.
Poseidon, in front-line NSCLC, was toplined in May as backing an overall survival benefit for Imfinzi plus chemo only if combined also with tremelimumab, an anti-CTLA-4 MAb Astra had largely deprioritised. Full data from the trial will be revealed for the first time at a World Lung plenary next Thursday, as well as featuring as the highlight of a press briefing on the same day.
Investors will scrutinise treme’s safety profile, and look for detail about why Poseidon succeeded when so many other treme studies failed; Poseidon did back the non-treme containing combo in PFS terms, a paradox that will need explaining. Perhaps Astra will also reveal further filing plans for Imfinzi, which does not carry a metastatic NSCLC label.
World Lung plenaries will also highlight Pharmamar/Jazz’s Atlantis, the potentially confirmatory SCLC study of Zepzelca that last December was said to have failed. The big risk here is that the FDA might now pull the drug from the market, though this seems unlikely.
China’s front line
A separate IO theme in first-line NSCLC is emerging via a trio of combo trials of Jiangsu Hengrui’s camrelizumab, Cstone’s sugemalimab and Shanghai Junshi’s toripalimab, all being presented on Monday, September 13.
The first and last are already marketed in China, as Airuika and Tuoyi respectively, but it is sugemalimab and toripalimab that might be of greatest interest to US investors. They have US licensees – EQRX and Coherus respectively – that seek to challenge Merck & Co’s Keytruda by competing on price.
The Gemstone-302 trial of sugemalimab and Choice-01 study of toripalimab are both showing PFS and, to an extent, OS benefits versus chemo alone, according to abstracts that World Lung has already made available. However, as these relate to relatively early data cuts, investors will keenly await more up-to-date results.
And the biggest question will be whether studies carried out in China might serve to support US approval even if, on a cross-trial basis, they show survival data broadly in line with Keytruda’s Keynote-407 and 189 studies. Investors should focus on baseline characteristics, benefit in PD-L1-negative patients, and choice of subsequent therapy in these Chinese front-line NSCLC trials.
|Selected World Lung 2021 oral presentations|
|PL02.01*||Imfinzi +/- tremelimumab + chemo||Astrazeneca||Poseidon||Treme combo toplined positive for OS|
|PL02.03*||Zepzelca||Pharmamar/Jazz||Atlantis||Failed trial; risk of FDA withdrawal?|
|PL02.05*||Tecentriq in adjuvant NSCLC||Roche||Impower-010||Already presented at Asco21; any more detail on PD-L1-negatives?|
|PL05.01||Mesothelin-targeted Car-T therapy||NA||NA||MSKCC overview|
|EGFR exon 20 insertion/cMet mutated NSCLC|
|OA15.01||Mobocertinib||Takeda||NCT02716116||Filed with FDA, 16 Oct 2021 Pdufa date|
|OA15.02||DZD9008||Dizal||Wu-Kong1||Important dataset at Asco 2021|
|OA15.03||Rybrevant||J&J||Chrysalis||cMet-mut NSCLC cohort; launched for EGFR exon 20 ins|
|OA15.04||Telisotuzumab vedotin||Abbvie/Seagen||NCT03539536||Study in cMet-mut NSCLC, EGFR w/t & mutant cohorts|
|OA07.03||Rubraca + Opdivo in 1L SCLC maintenance||Clovis||NCT03958045||Investigator-initiated uncontrolled ph2|
|OA09.02*||Tecentriq + chemo in NSCLC brain mets||Roche||Atezo-brain||Spanish Lung Cancer Group study|
|OA13.01*||Tecentriq + chemo neoadjuvant, then Tecentriq maintenance, mesothelioma||Roche||S1619||NCI study (uncontrolled ph1); note Checkmate-743|
|MA13.01||Camrelizumab + apatinib in 1L NSCLC||Jiangsu Hengrui||NCT03083041||Has 1L NSCLC chemo combo label in China|
|MA13.07||Sugemalimab + chemo 1L NSCLC||EQRX/Cstone||Gemstone-302||Possible low-cost competitor in US|
|MA13.08||Toripalimab + chemo 1L NSCLC||Coherus/Shanghai Junshi||Choice-01||Toplined positive, but questions over US approvability & benefit in PD-L1 negatives|
|MA02.06||Pelcitoclax (APG-1252) + Tagrisso||Ascentage Pharma||NCT04001777||Low-key Chinese asset in EGFR TKI-resistant NSCLC|
|MA03.02||Datopotamab deruxtecan||Daiichi/Astrazeneca||TROPION-PanTumor01||NSCLC cohort; breast cancer dataset revealed earlier|
|Note: *also features at press briefings. Source: IASLC/World Conference on Lung Cancer.|
Finally, a mini oral session devoted to EGFR exon 20 insertion and cMet mutated NSCLC on Sunday will be of interest to those focused on this burgeoning targeted therapy niche.
Dazal’s DZD9008 already made a big splash at Asco, thanks to which the group will surely be fielding calls from interested partners. J&J’s bispecific Rybrevant is approved, while Takeda’s small-molecule contender mobocertinib has an October 26 US FDA action date. Updates for all three feature at World Lung, Rybrevant’s concerning the Met exon 14 skipping cohort of its registrational Chrysalis trial.
However, a fourth asset, Abbvie/Seagen’s antibody-drug conjugate telisotuzumab vedotin, might get the most attention, given that very little clinical data on it have been published so far. The World Lung abstract in cMet-positive second-line NSCLC cites remission rates of 25-54% in EGFR wild type patients, and 0-18% in EGFR mutants.
September will also see two AACR special conferences, devoted to ovarian and pancreatic cancers, not to mention Esmo. After that the Triple Meeting, SITC, Ash and San Antonio Breast Cancer round out 2021. World Lung should provide a decent warm-up.
The World Conference on Lung Cancer takes place in virtual format on September 8-14.