The 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO 2018) is upon us, and it’s about as close to Christmas as I get in my line of work. There’s so much data presented here, with thousands of abstracts delivered to an audience of some 30,000 healthcare professionals, that it’s tough to keep up.
Of course, I’ll be focused as you will on the big, high-profile presentations with obvious impact on investors over the next few months. But in order to make better forecasts about these companies, and in order to identify promising new leads on cancer investments, we need to pay attention to the smaller studies, as well.
This series includes 4 abstracts per day, but note that subscribers to the Total Pharma Tracker get a bonus abstract discussion. Learn more about this service here!
TPT Exclusive: PARP inhibition shows signs of life in brain cancer
Described here is a positive-outlook study on the use of PARP inhibitors in glioblastoma. However, this one is exclusive for subscribers to the Total Pharma Tracker. Learn more about a free trial of this service here.
Puma and Roche could have a winner combo with next-gen dual-HER2 combo
Abstract 1027 – NSABP FB-10: Phase Ib dose-escalation trial evaluating trastuzumab emtansine (T-DM1) with neratinib (N) in women with metastatic HER2+ breast cancer (MBC)
Roche (RHHBF) and Puma Biotechnology (PBYI)
Dual blockade of HER2 is currently an important treatment option for metastatic, HER2-positive breast cancer, thanks to the results from CLEOPATRA demonstrating significant survival benefit when adding pertuzumab to trastuzumab chemotherapy for first-line treatment. Naturally, alternative regimens need to be explored in various settings. This phase 1b study combined the HER2 antibody drug conjugate T-DM1 with PBYI’s small molecule pan-EGFR inhibitor neratinib. The 27 patients in this study had received prior trastuzumab-pertuzumab anti-HER2 therapy and grew resistant. Out of 20 patients evaluable for efficacy, the overall response rate was 64%, with 3/20 achieving a complete response. The combination was generally well tolerated and feasible.
Although very preliminary, the combination’s response rate compares favorably with that found in EMILIA, which looked at T-DM1 alone for previously treated metastatic breast cancer (it was 43.6%). Therefore, it would appear as though this trial supports the further exploration of this dual-HER2 blockade approach to salvage therapy, and I won’t be surprised if we see PBYI march in that direction in the long term.
Outlook: Neutral in the short term, but positive in the long term
Gilead finally moving forward with its MMP?
Abstract 1032 – Results from a phase I study of andecaliximab in combination with paclitaxel in patients with previously untreated metastatic breast cancer
Gilead Sciences (GILD)
GILD, in continuing to try and build any momentum it can in the oncology space, is exploring its MMP9 antibody andecaliximab in several tumor areas. Based on preclinical work, it seemed as though andecaliximab might have synergistic activity with standard chemotherapy breast cancer, which led to this phase 1 study in patients with previously untreated metastatic breast cancer to receive andecaliximab in combination with paclitaxel.
The overall response rate for this combination was 53%, with a median progression-free survival of 7.4 months. Median overall survival had not been reached as of the data pull. Although this was a small cohort of patients, the response rates observed here compare favorably with those seen historically using paclitaxel alone (31% in one study). The combination was also associated with a serious adverse event rate of 33%, with notable adverse events including kidney injury and atrial fibrillation. So the safety data here might be a little shaky, but the efficacy findings definitely warrant further exploration. As I stated in a previous article (prior to the KITE buyout), andecaliximab represents an important way forward for GILD, and this might be one more channel it can chart, although I suspect it will take some time.
Outlook: Neutral to positive
Bayer gives a headfake in direction to its kinase inhibitor program
Abstract 2047 – Updated results of REGOMA: A randomized, multicenter, controlled open-label phase II clinical trial evaluating regorafenib in relapsed glioblastoma (GBM) patients (PTS).
Bayer (BAYZF) (BAYRY)
BAYRY’s multikinase inhibitor regorafenib has achieved a measure of success in several gastrointestinal cancers, including approval in colorectal cancer and hepatocellular cancer. Expansion of the label now appears to be BAYRY’s goal in the near future, and it looks like, of all things, glioblastoma may be it. The REGOMA trial is a randomized, phase 2 study testing regorafenib in patients with relapsed disease. 119 patients were randomized to either regorafenib or lomustine following progression on surgery and the Stupp regimen (radiotherapy plus temozolomide). Regorafenib significantly improved median overall survival compared with lomustine (7.4 months versus 5.6 months), and 12-month overall survival rate was doubled with regorafenib.
Progression-free survival and disease control rates were also improved with regorafenib. Overall, regorafenib treatment led to a modest increase in toxicity, with a reported incidence of grade 3 or higher adverse events being seen in 56% and 40% of patients receiving regorafenib and lomustine, respectively. Overall, this phase 2 study provides an interesting look at the development of regorafenib in glioblastoma, and I expect that the planned phase 3 trial will yield similar results and lead to eventual approval. Therefore, I view this abstract as significantly favorable!
Pfizer’s triplet may push the field of hormone-positive metastatic breast cancer further still
Abstract 1040 – Phase Ib study of gedatolisib in combination with palbociclib and endocrine therapy (ET) in women with estrogen receptor (ER) positive (+) metastatic breast cancer (MBC)
In this abstract, PFE described in brief the rationale for combining an inhibitor of PI3K/mTOR signaling, a CDK4/6 inhibitor, and endocrine therapy in tumors that harbor PIK3CA mutation. Therefore, the company conducted a phase 1b trial assessing the triplet of its developmental PI3K inhibitor gedatolisib along with palbociclib and endocrine therapy in hormone-positive breast cancer.
A total of 35 patients received the recommended dose of 180 mg gedatolisib. Partial response rate ranged from 20% to 33%, depending on the endocrine therapy partner. The triplet was associated with a high rate of nausea and stomatitis. However, the risk of dose-limiting toxicity was relatively low, with 8 patients experiencing a dose-limiting toxicity in cycle 1 of treatment.
Overall, these findings indicate that the triplet regimen is feasible, which is good news to me since mTOR inhibition (with Novartis’ (NYSE:NVS) everolimus) is associated with potentially severe stomatitis that can set patients back. I would definitely worry that adding more to that kind of protocol would be prohibitively toxic. But it looks as though PFE has a possible inroad to getting its hands on every treatment approach to hormone-positive breast cancer.
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