The American Society of Clinical Oncology (ASCO) annual meeting, which closed last week, had fewer standout presentations than in previous years but the many hundreds of studies that were described did serve to demonstrate the sheer volume of clinical cancer research that is currently underway.

The price-weighted BioWorld Cancer Index, which comprises 21 biotech companies developing cancer therapies, increased in value a modest 4% during the conference period showing that investors are still bullish about the space. The second part of this feature reports on how the equities of public biopharmaceutical companies that are developing cancer therapies performed during the week of the event.

The BioWorld Cancer Index does not include big pharmaceutical companies such as Bristol-Myers Squibb Co., Pfizer Inc. and Merck & Co. Inc.; rather, the main selection criterion is that a firm’s pipeline must consist mainly of candidate cancer therapies that are under development.

By market close Thursday, the index was trading up 12% year-to-date in line with the general markets where the Nasdaq Composite index is up almost 15% and the Dow Jones Industrial Average up over 10% in the same period. (See BioWorld Cancer Index, below.)

Leading gainers

Cambridge, Mass.-based Blueprint Medicines Corp. was the leading gainer in the group with its shares (NASDAQ:BPMC) jumping 19% thanks to a strong showing at ASCO. The precision therapy company focused on genomically-defined cancers, rare diseases and cancer immunotherapy, reported updated data from an ongoing registration-enabling ARROW trial of BLU-667 in patients with RET (rearranged during transfection)-altered cancers. The data show durable clinical activity in patients with RET-altered non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and other cancers. BLU-667 is a potent and highly selective oral inhibitor of RET fusions and mutations, including predicted resistance mutations.

The new results, the company said, support its plans to submit an initial new drug application (NDA) to the FDA for BLU-667 for the treatment of patients with RET-fusion NSCLC previously treated with platinum-based chemotherapy in the first quarter of 2020, and an NDA for the treatment of patients with RET-mutant MTC previously treated with an approved multi-kinase inhibitor (MKI) in the first half of next year.

“Importantly, the company indicated that BLU-667 is active in patients failing LOXO-292, with a 50% response rate (2/4 partial responses),” noted SVB Leerink analyst Andrew Berens. “This finding is important because it expands the overall opportunity for both drugs, and also lessens the urgency that BLU-667 needs to be superior to LOXO-292 to have a meaningful market presence.”

The presented data included 120 patients with RET-fusion NSCLC, 64 patients with RET-mutant MTC and 12 patients with other RET-altered cancers (nine papillary thyroid cancer (PTC), two pancreatic cancer and one intrahepatic bile duct carcinoma) enrolled in the ARROW trial as of a data cutoff date of April 28, 2019. The patients with RET-fusion NSCLC and RET-mutant MTC received a starting dose of 400 mg once daily (QD), which is the recommended phase 2 dose (RP2D). Patients with other RET-altered cancers were included regardless of starting dose.

At the meeting, the company also reported data demonstrating clinical activity and favorable tolerability from the registration-enabling NAVIGATOR trial of avapritinib in patients with PDGFRA Exon 18 mutant gastrointestinal stromal tumors (GIST) and fourth-line GIST. Data from the program showed that patients with PDGFRA Exon 18 mutant GIST achieved an objective response rate (ORR) of 86% while the median duration of response (DOR) was not reached. Meanwhile, patients with fourth-line GIST had an ORR of 22% while the median DOR was 10.2 months.

The company said it plans to submit an NDA for avapritinib later this month and subsequently, file a regulatory application in Europe during third-quarter.

TG Therapeutics Inc. also saw it shares climb (NASDAQ:TGTX) 12%. It presented positive interim data from an ongoing single-arm marginal zone lymphoma (MZL) cohort of its phase IIb UNITY-NHL trial currently evaluating umbralisib as a single agent in patients with relapsed/refractory MZL. Umbralisib is an oral, once-daily PI3K delta inhibitor currently under development for the treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia.

The MZL cohort of UNITY-NHL enrolled patients with relapsed or refractory MZL who had received prior treatment with one or more lines of therapy including at least one anti-CD20 regimen. In August 2018, the trial completed enrollment with 69 treated patients. The interim data included safety and tolerability data on all 69 treated patients (safety population) and efficacy data on 42 patients who were enrolled at least 9 cycles (28-days) prior to the data cut-off date. It was found that the ORR was 52% (N=42), with complete response (CR) rate of 19%, by central independent review committee (IRC).

Disappointing results

Rockville, Md.-based Macrogenics Inc. saw its shares (NASDAQ:MGNX) swoon 20%. At ASCO the company reported the results from the phase III SOPHIA study of margetuximab in patients with HER2-positive metastatic breast cancer who had previously been treated with anti-HER2-targeted therapies.

The study met its first sequential primary endpoint of progression-free survival (PFS). The median PFS of patients treated with margetuximab and chemotherapy was 5.8 months compared to 4.9 months in patients treated with trastuzumab and chemotherapy (hazard ratio [HR]=0.76; 95% CI: 0.59-0.98; p=0.033). Among the approximately 85% of patients carrying the CD16A 158F allele, a pre-specified exploratory subpopulation in the study, PFS was prolonged by 1.8 months in the margetuximab arm compared to the trastuzumab arm (6.9 months versus 5.1 months; HR=0.68; 95% CI: 0.52-0.90; p=0.005). The ORR, a secondary outcome measure in the SOPHIA study, was 22% in the margetuximab arm (95% CI: 17.3-27.7%) compared to 16% in the trastuzumab arm (95% CI: 11.8-21.0%).

Jonathan Chang, an analyst at SVB Leerink said that, “We believe the stock reaction reflected disappointment in the OS data although the data are not yet mature. Management expressed confidence in achieving a survival benefit as the data mature despite the modest PFS benefit based on the immune-based mechanism of margetuximab.”

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