Researchers identified a new biomarker called mismatch repair (MMR) deficiency, which predicts superior response to anti-PD1 therapy. The ORR was 62% in MMR-deficient patients compared with 0% in MMR-proficient patients. Tumors with MMR deficiency harbor many more mutations than tumors without such repair defects. Tumors with more mutations are more likely to be recognized as foreign by the immune system.
Nivolumab showed promising activity in advanced liver cancer in a Phase I/II trial. The ORR in 42 evaluable patients was 19%, including two with complete responses. 68% of patients had previously received sorafenib. The overall survival rate at 12 months was 62% with nivolumab. Sorafenib is currently the only FDA-approved systemic treatment for advanced liver cancer. The response rate with sorafenib in this setting is only 2%.
About one year ago, Puma Biotechnology (NASDAQ: PBYI) skyrocketed 295% after reporting the top-line results from the Phase III trial (ExteNET) of neratinib in HER2+ early breast cancer. At the ASCO2015, the company provides a primary analysis at 2 years of ExteNET trial. IDFS in the neratinib arm was 93.9% compared to 91.6% for placebo. The absolute difference of only 2.3% was lower than the market expected. Moreover, the drug caused high rates of Grade ≥ 3 diarrhea (40%).
Oncothyreon’s (NASDAQ: ONTY) ONT-380, in combination with capecitabine/trastuzumab, showed promising results in HER2+ metastatic breast cancer patients previously treated with trastuzumab and T-DM1. The ORR in 27 evaluable patients was 52%. In another Phase Ib trial, 22 breast cancer patients with CNS metastases were treated with ONT-380 plus T-DM1 or ONT-380 plus capecitabine/trastuzumab. One patient had a complete response; four had a partial response and nine has a stable disease. ONT-380 selectively inhibits HER2 without significant inhibition of EGFR, avoiding EGFR-like side effects. No Grade ≥ 3 diarrhea has been seen.
In April 2015, Clovis Oncology (NASDAQ: CLVS) received Breakthrough Therapy designation for PARP inhibitor rucaparib for the treatment of BRCA-mutated ovarian cancer. At the ASCO2015, the company posted positive data from a Phase II trial. The ORR in 32 patients was 82%. The median PFS was 9.4 months. Rucaparib appears superior to AstraZeneca’s olaparib. The accelerated approval of olaparib is based on an ORR of 34% and a median DOR of 7.9 months.
ImmunoGen’s (NASDAQ: IMGN) IMGN853 demonstrated encouraging clinical activity in heavily pretreated patients with FRα positive platinum-resistant ovarian cancer. The ORR was 53% (n=9/17) which included one complete response and eight partial responses. IMGN853 is antibody-drug conjugate that comprises an anti-FRα antibody conjugated with DM4.