Welcome to your weekly digest of approaching regulatory and clinical readouts. Phase III results are expected by mid-year of Celgene’s Revlimid in relapsed/refractory follicular lymphoma, a disease where the drug has already failed first line. With generic competition looming as soon as 2020, the pressure is on to expand into new indications.
Meanwhile, topline pivotal data are due for Roche’s Tecentriq in combination with Cotellic in metastatic colorectal cancer. Merck has first-mover advantage with Keytruda in a subgroup of patients, but Roche’s approach could target a larger market.
With generic competition looming Celgene’s cash cow Revlimid needs to expand into new indications, but at the end of last year it stumbled in the phase III Relevance trial in first-line follicular lymphoma, a setting that Leerink analysts noted could have been worth $1.3-1.4bn in peak sales (Pharma news over the Christmas period, January 2, 2018).
The next test will be in relapsed/refractory follicular lymphona, with data due by mid-year from the phase III Augment study pitting Revlimid plus Rituxan versus Rituxan alone. Knocking out chemotherapy in the comparator arm could give the study a greater chance of success, but the relapsed setting is a small commercial opportunity, with Leerink estimating $600-700m in peak sales.
The double-blind, randomised trial has enrolled 358 patients, and aims to demonstrate superiority in progression-free survival as primary endpoint, with overall survival, response rates and duration of response as secondary measures.
Celgene's other recent setbacks include cutting 2020 guidance last October and failure of its Crohn’s disease candidate mongersen in phase III, while its multiple sclerosis hope ozanimod, seen as one of the biggest potential launches of 2018, recently received a refusal-to-file letter. Acquisitions of Impact Biomedicines and Juno show that Celgene is serious about filling the Revlimid void.
Colorectal cancer test
A phase III trial known as Cotezo or Imblaze-370 should report topline data in the first half of the year. This tests Roche’s Tecentriq with or without the MEK inhibitor Cotellic versus Stivarga in patients with second or third-line metastatic colorectal cancer.
The hypothesis behind the combination is that Cotellic might sensitise tumours to Tecentriq by increasing MHC I expression on tumour cells, promoting cytotoxic T cell accumulation. This could improve efficacy in microsatellite-stable subjects, who make up some 80-85% of colorectal cancer patients and have minimal response to PD-(L)1 inhibitor monotherapy.
Imblaze-370 enrolled 360 subjects, specifying that only up to 5% can be microsatellite instability (MSI)-high; the remainder were microsatellite-stable. The primary endpoint is overall survival, with secondaries including PFS, complete response, partial response and duration of response.
At the Asco-GI conference in January a phase Ib trial yielded an ORR of 8% from 84 evaluable patients, while the median PFS was 1.9 months and median OS was 10 months. 38 of the patients had known MSI status at baseline: 29 were stable, eight were MSI-low and one was MSI-high.
Leerink analysts noted that this OS compared favourably with the 6.4 months seen in Stivarga’s phase III trial, Correct, in third-line patients. The analysts give a 40% probability of success for Imblaze-370.
Merck’s Keytruda was the first checkpoint inhibitor to gain US approval in a subgroup of second-line colorectal cancer patients, and also in any solid tumour patients who are either second line or have no alternative treatment – both as long as they are MSI-high or have mismatch repair deficiency (Keytruda’s next advance encroaches on Opdivo and Tecentriq territory, May 24, 2017).
Three months later Bristol-Myers Squibb’s Opdivo also gained approval in this biomarker setting, but limited to colorectal tumours.
Most patients in Roche’s Imblaze-370 trial are microsatellite-stable, so if the combination works it could ultimately target a bigger market.
American College of Cardiology conference