AACR Annual Meeting 2015 Highlights

Pembrolizumab is better than ipilimumab as first-line therapy for patients with advanced melanoma. ORR was 33% for pembrolizumab and 12% for ipilimumab. The 6-month OS rates were 85-88% for pembrolizumab arms and 75% for ipilimumab.

Pembrolizumab showed an ORR of 24% and a disease control rate of 76% in 25 patients with pleural mesothelioma. 80% 0f patients had received standard chemotherapy (platinum plus pemetrexed). There is no approved second-line treatment.

The relationship between ORR and PDL1 expression was verified in patients with NSCLC. PFS and OS were longer in patients with membranous PDL1 expression in ≥50% of tumor cells (PS≥50%).

According to the preliminary Phase I results of CART-meso, CAR-T therapy appears safe and feasible in advanced solid tumors. Anti-tumor efficacy was observed in 2 out of 5 patients.

Immunocore’s TCR therapy, IMCgp100, showed an ORR of 25% (4/16) in patients with advanced melanoma. One partial response was observed in an ipilimumab refractory patient. Two of the partial responses have lasted more than 12 months.

Atara Biotherapeutics presents Phase II clinical data of EBV-CTLs in patients with EBV-associated lymphoproliferative disorder (EBV-LPD). EBV-LPD is one of the most concerning complications of blood stem cell transplantation. In the two trails, 50-59% of patients had a complete response. Most importantly, 81% of patients had failed prior rituximab.

Combining anti-CD40 mAb CP-870893 with anti-CTLA4 mAb tremelimumab improves response rates and overall survival in patients with metastatic melanoma. ORR was 27.3%, with mOS of 26.1 months.

Combining mTORC1/2 inhibitor AZD2014 with paclitaxel showed better outcome in ovarian and lung cancer. Of 7 patients with heavily pre-treated ovarian cancer, 3 had partial responses. Of 5 squamous NSCLC pre-treated with docetaxel, 2 had partial responses.

Chk1 inhibitor GDC-0425 may enhance gemcitabine efficacy in solid tumors with p53 mutation. The trial enrolled 40 patients with a variety of solid tumors. Three patients including one patient with p53 mutated triple-negative breast cancer (TNBC) had partial responses. The partial response in TNBC has lasted more than 10 months.

In July 2014, Roche acquired Seragon Pharmaceuticals and its selective estrogen receptor degraders for $1.725 billion. Now, Roche provides Phase I results of GDC-0810 (ARN-810) in ER+/HER- metastatic breast cancer at AACR2015. In the trial, 13 of 31 (42%) patients achieved stable disease > 6 months.

Adding a PI3K inhibitor to letrozole may restore the sensitivity of ER+ breast cancer to antiestrogen therapy. In the Phase Ib trial of BYL719, 26 patients with ER+/HER2- metastatic breast cancer refractory to previous endocrine therapy were accrued. 18 patients had prior aromatase inhibitor therapy. In the trial, 19% of patients experienced a partial response, and 43% of patients had stable disease.

Combining mTORC1/2 inhibitor AZD2014 with fulvestrant showed clinical benefit for patients with ER+ metastatic breast cancer. In the 49 patients with measureable disease, 9 confirmed and 3 unconfirmed partial responses were observed. Of the 66 patients, 31 had clinical benefit.

Merrimack Pharmaceuticals updates Phase I results of HER2-targeted liposomal doxorubicin in HER2 positive metastatic breast cancer. In patients treated with ≥30 mg/m2 MM-302 alone or in combination with trastuzumab, the response rate was 12% and median PFS was 7.6 months. Merrimack believes MM-302 plus trastuzumab is more effective than standard chemotherapy plus trastuzumab.

Olaparib have anti-tumor activity in a sub-population of metastatic castration-resistant prostate cancer patients. In the TOPARP trial, patients who had failed prior docetaxel and abiraterone were treated with olaparib. Overall, 16 of 49 patients experienced a response. Mutations in DNA repair genes were detected in 15 of 49 patients. Among these 15 patients with mutations, 13 responded to olaparib.

Genentech’s anti-PDL1 mAb MPDL3280A showed clinical activity in patients with metastatic triple-negative breast cancer. Among 21 PDL1 positive (IHC2 or 3) patients, ORR was 24%, and the 24-week PFS rate was 33%.

Adding nivolumab to ipilimumab improved clinical response compared to ipilimumab alone in patients with advanced melanoma. In BRAF wild-type patients, ORR was 60% in the combination group vs. 11% in the ipilimumab group. A higher rate of adverse events was observed in the combination group compared to ipilimumab alone, leading to more frequent discontinuation. However, patients who discontinued the combination due to toxicity had a 67% response rate.

Adaptimmune presents preliminary results of TCR therapy targeting NY-ESO-1 in patients with synovial sarcoma. Of 8 patients whose follow-up is sufficient to assess response, 4 experienced objective responses (1CR, 3PR).


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