The promise of combining PARP inhibitors and checkpoint inhibitors in cancer is exciting oncologists, and Bristol-Myers Squibb and Clovis Oncology have joined forces to test a pairing that will go head-to-head with AstraZeneca and Merck & Co.
The wide-ranging collaboration with BMS’ PD-1 drug Opdivo (nivolumab) given alongside Clovis’ PARP inhibitor Rubraca (rucaparib) in phase II and III trials involving a range of tumour types, including the first-line maintenance treatment of advanced ovarian cancer and triple-negative breast cancer (TNBC) and metastatic, castration-resistant prostate cancer (CRPC).
The new agreement comes hard on the heels of an $8.5bn alliance between AZ and Merck that will see the latter’s PD-1 blocker Keytruda (pembrolizumab) given alongside AZ’s PARP drug Lynparza (olaparib) in a wide range of tumour types, including breast cancer. Merck previously put a combination of Opdivo and Tesaro’s new PARP inhibitor Zejula (niraparib) through its paces.
Interest in combining the two cancer drug types comes from the finding in animal studies that PARP inhibitors up-regulate the expression of PD-L1 on tumours, which in turn should make them more vulnerable to attack by PD-1/PD-L1-targeting drugs. The hope is that the approach could be synergistic, with the effects of the two classes greater than the cumulative effect of each used alone.
Delving into the detail of the new deal, BMS and Clovis will test Rubraca alone, Opdivo alone and the combination in newly-diagnosed patients with stage III/IV high-grade ovarian, fallopian tube, or primary peritoneal cancer who have completed platinum-based chemotherapy.
The TNBC study will look at the duo, Rubraca alone, Opdivo alone and chemotherapy in patients with stage IV or recurrent locally advanced inoperable tumours associated with a homologous recombination deficiency (HRD).
A phase II trial of Opdivo plus Rubraca in CRPC will be conducted as an arm of a larger BMS study, said the partners.
Credit Suisse previously predicted that Lynparza will lead the PARP inhibitor market in 2020, with sales of $1.6bn and just ahead of Rubraca, although they see rapid uptake for niraparib from a standing start with more than $1bn in sales in that year.
The picture could dramatically change if the drugs fulfil their promise in combination with PD-1/PD-L1-targeting drugs, allowing them to ride on the shirt-tails of the checkpoint inhibitor class. Opdivo and Keytruda continue to grow at breakneck speed, bringing in $2.32bn and $1.47bn respectively in the first six months of the year.