Last year Merck & Co paid over $1bn to buy Peloton Therapeutics on the back of data that, while very impressive, came from just 55 subjects. An update from this first-in-human study on Saturday should give a better idea whether this was money well spent.
The venue for the presentation will be the Asco Genitourinary Cancers Symposium, which starts in San Francisco tomorrow and continues with presentations into Saturday. Also on the radar are clinical results with Cabometyx, which look to reverse Exelixis’s 2014 failure in prostate cancer, though investors should look for more information on a treatment-related death mentioned in the abstract.
Exelixis’s Cosmic-021 trial combines Cabometyx with Roche’s Tecentriq, and its Asco-GU abstract refers to a very early data cut in castration-resistant prostate cancer subjects who had progressed on novel hormone therapy. This showed a 32% overall remission rate for the combo.
Cosmic-021 aims to enrol 1,732 patients across various cancers, but for now only the uncontrolled combo data are available, so a comparison is tricky. Stifel analysts reckon 8-18% remission rates in Merck’s Keynote-365 study of Keytruda plus Lynparza provides a benchmark of sorts.
Investors will want to know why Cosmic-021 shows promise when in the similar setting of Cosmic-1 Cabometyx failed against prednisone (Exelixis wiped out after Comet-1 crash lands, September 2, 2014). They should also ask about the treatment-related death from dehydration of a 90-year-old Cosmic-021 subject.
Riding in the Peloton
Meanwhile, the Asco-GU abstract for Merck’s MK-6482 relate to a May 2019 cut-off, and were already known at the time of Peloton’s $1.05bn takeout: a 24% ORR in 55 subjects with second-line or later renal cell carcinoma. The presentation on Saturday should provide a more up-to-date dataset.
MK-6482 is claimed to be the first small-molecule inhibitor of HIF-2α, and another closely watched indication for it is von Hippel-Lindau disease. According to EvaluatePharma sellside consensus MK-6482 has yet to be included in most analysts’ models, so more validation of the Peloton takeover is keenly awaited.
|Selected Asco-GU 2020 abstracts|
|Thursday 13 February|
|ADXS-PSA||Advaxis/Merck & Co||Anti-PSA vaccine||Keytruda combo in mCRPC||Keynote-046 part B||126|
|Pasotuxizumab||Bayer/Amgen (ex Micromet)||Anti-PSMA BiTE||First-in-human study in mCRPC||NCT01723475||124|
|Talabostat||Bioxcel||DPP & FAP inhibitor||Keytruda combo in mCRPC||NCT03910660||140|
|SHR3680||Jiangsu Hengrui||Antiandrogen||First-in-human study in mCRPC in China||NCT02691975||90|
|Cabometyx||Exelixis||TKI||Tecentriq combo in mCRPC||Cosmic-021 cohort 6||139|
|Friday 14 February|
|Padcev||Seattle Genetics/Astellas||Anti-nectin-4 ADC||Keytruda combo in 1L urothelial cancer||EV-103||441|
|Guadecitabine||Otsuka (ex Astex)||DNMT inhibitor||Platinum-refractory germ cell tumors||NCT02429466||408|
|Infigratinib||Novartis||FGFR inhibitor||3/4 CRs in FGFR3-altered nonmuscle-invasive bladder cancer||NCT02657486||510|
|Saturday 15 February|
|MK-6482||Merck & Co (ex Peloton)||Oral HIF-2α inhibitor||First-in-human stdy in ≥2L RCC||NCT02974738||611|
|Sitravatinib||Mirati||TKI||Opdivo combo in 2L RCC||NCT03015740||612|
Other Asco-GU abstracts that have caught analysts’ eyes include an update on Seattle Genetics’ EV-103 study of Padcev, and Mirati’s sitravatinib plus Opdivo combo in advanced renal cancer.
The latter yielded a 38% ORR, which Leerink said was promising and beat the 20-22% seen with Opdivo or sitravatinib monotherapy in another study. Mirati, of course, is an all-in bet on the Kras inhibitor MRTX849, so sitravatinib could give the sellside reason to raise target prices yet further.
Padcev, Seattle/Astellas’s anti-nectin-4 antibody drug conjugate, secured accelerated US approval in December for anti-PD-(L)1-relapsed urothelial cancer on the basis of the EV-201 trial. EV-103 is a front-line study in combination with Keytruda, and had already impressed at last year’s Esmo meeting.
The Asco-GU abstract relates to a June data cut, with ORR now 73% (71% at Esmo) and a 12.3-month median progression-free survival. Since Tecentriq plus chemo yielded 8.2 months of mPFS in Imvigor-130 the updated data presentation, due on Friday, should make EV-103 one of the highlights of Asco-GU.