ASCO 2018

Breast cancer has been one area where checkpoint inhibitors have not yet gained traction – but that might be about to change following results announced by Tesaro at the American Society of Clinical Oncology’s conference in Chicago.

Tesaro has developed its own PD-1 checkpoint inhibitor and wants to combine it with its approved PARP inhibitor, Zejula, and is looking to take the combination into later stage clinical trials.

Trials of the PARP/PD-1 combination have so far taken place with Merck’s Keytruda, but Tesaro wants to avoid striking an expensive licence deal with one of the big pharma's that already market checkpoint drugs.

Data released at ASCO 2018 is from TOPACIO, a phase 1/2 trial in ovarian cancer or triple negative breast cancer (TNBC).

Following dose finding in phase 1, a Zejula (niraparib) pill was administered daily at a dose of 200 milligrams in combination with 200mg of Merck’s Keytruda on day one of each 21-day treatment cycle, in the two patient cohorts of ovarian or breast cancer.

Investigators on the TOPACIO trial were measuring objective response rate (ORR), duration of response (DOR) and disease control rate (DCR).

In 55 breast cancer patients ORR was 28%, and DCR was 50%. In patients with the BRCA mutation, ORR was 60% and DCR was 80%, with a median progression-free survival of 8.3 months.

In the combined BRCAmut plus HRRmut population, ORR was 55% and DCR was 80%, with median PFS of 6.4 months. Median DOR has not been reached with 62% (8/13) of responders remaining on treatment, including five patients with long-term, ongoing clinical benefit for approximately one year.

The PFS figure compares favourably with standard chemotherapy, which usually stops the disease from spreading for three to five months.

The 60 evaluable patients with ovarian cancer were heavily pre-treated, with one to five lines of prior therapy – but data indicated an overall response rate of 25%, and disease control rate of 67%.

In a cohort with BRCA mutations, ORR was 25%, with DCR of 63%, and the story was similar in those with BRCA wild-type mutations with ORR and DCR at 24% and 65% respectively.

Response rates were not dependent on biomarker status or platinum status. ORR was 23% (7/30) in platinum-resistant ovarian cancer patients, 24% (4/17) in platinum-refractory patients and 31% (4/13) in patients who were platinum ineligible per investigator’s assessment. Median DOR was 9.3 months, with nine patients remaining on treatment.

With anaemia and low platelet count the most common adverse events, Tesaro has had a successful discussion with FDA and is planning a registration study for the Zejula and TSR-042 combination.

Tesaro also published data from the QUADRA trial which it hopes will support a label expansion for Zejula in pre-treated patients with ovarian cancer without BRCA mutations.

Tesaro said it plans pivotal trials for the combination of Zejula and TSR-04 in the ovarian and breast cancer indications, and label expansion filing for Zejula monotherapy with the FDA in the fourth quarter.

Loxo

The biotech Loxo has also made waves at ASCO 2018, after its experimental cancer drug LOXO-292, targeting RET mutations, improved on previously-announced data.

Loxo last month released data showing LOXO-292 shrank tumours in 69% of advanced cancer patients, regardless of whether their disease began in the lung, pancreas, or thyroid.

The new results from the same study released at ASCO 2018 showed an overall response in 77% of those with RET fusion mutations.

However as these are only phase 1 results, there is a long way to go before the drug can reach the market.