This year the premier oncology event – the annual meeting of the American Society of Clinical Oncology (ASCO), is just around the corner. The 53rd annual ASCO meeting will be held from June 2 to June 6 at the McCormick Place in Chicago, Ill.
Historically, the goal of ASCO was to foster communication among oncology-related subspecialties, as well as the exchange of a wide range of ideas related to cancer. This year expect even more coverage and exchange of ideas designed to benefit cancer patients. This year expect more information about targeted, personalized medicine, including antibody-drug conjugates, PD-1s and small-molecule drug conjugates as well as companion imaging agents for focused, personalized, diagnostics.
DS-8201 and U3-1402
Daiichi Sankyo will present research new data on its lead antibody-drug conjugates DS-8201 and U3-1402. In particular, clinical results from a phase I study of DS-8201 will be discussed during a Clinical Science Symposium on June 5 at 9:45 a.m. CT. DS-8201 and U3-1402 use Daiichi Sankyo’s proprietary linker-payload technology.
DS-8201 is an investigational ADC in phase I clinical development for HER2-positive advanced or metastatic breast cancer or gastric cancer, HER2-low-expressing breast cancer and other HER2-expressing solid cancers. The U.S. Food and Drug Administration (FDA) granted Fast Track designation to DS-8201 for the treatment of HER2-positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2-targeted therapies including ado-trastuzumab emtansine (T-DM1).
U3-1402 is an investigational and potential first-in-class ADC currently in phase I clinical development for HER3-positive metastatic or unresectable breast cancer.
Overexpression of epidermal growth factor receptors (EGFR), such as HER2 and HER3, can play a role in cancer cell development, including breast cancer.  Statistics show that one in five breast cancers overexpress HER2, which is associated with more aggressive disease. Additionally, studies show that approximately 50 to 70% of breast cancer tumors have detectable levels of HER3.  Patients living with invasive breast cancer with high levels of HER3 may face a significantly worse prognosis and decreased survival.
Depending on several factors, including the biomarker classification (HR+, HER2+ or triple negative), breast cancer is typically treated with various combinations of surgery, radiation, chemotherapy, hormone therapy or targeted therapy.  But many HER2-positive tumors progress to the point where no currently approved HER2-targeting treatments can continue to control the disease.  Furthermore, there is no HER2-targeting therapies approved for HER2-weak positive tumors (IHC2+/ISH negative or IHC+) and no approved HER3-targeting therapy options. Hence, a better understanding of HER3 regulation should improve the strategies to therapeutically target HER3 for cancer therapy.
Promising safety and efficacy data from monotherapy and combination studies with mirvetuximab soravtansine in patients with folate receptor alpha (FRα)-positive epithelial ovarian cancer (EOC) will be presented during the 2017 ASCO meeting.
These data include results from pooled analyses of three Phase I expansion cohorts and from a Phase Ib/II study, FORWARD II, evaluating mirvetuximab soravtansine in combination with Avastin® (bevacizumab), carboplatin, Doxil® (pegylated liposomal doxorubicin), or Keytruda® (pembrolizumab).
Data from the pooled analyses demonstrate the safety and efficacy profile of mirvetuximab soravtansine in the patient population eligible for the ongoing Phase III registration trial, FORWARD I. These data include 113 EOC patients treated with mirvetuximab soravtansine in three expansion cohorts in the Phase 1 trial. In the subset of 36 patients meeting the key eligibility criteria for FORWARD I, which includes patients with platinum-resistant disease and medium or high levels of FRα and who have received up to three prior lines of therapy, the confirmed overall response rate (ORR) was 47% (95% CI 30, 65) and median progression-free survival (mPFS) was 6.7 months (95% CI 4.1, 8.3).
“The data observed with mirvetuximab compare favorably with outcomes typically achieved with currently available single-agent therapies for platinum resistant ovarian cancer. Current single-agent therapies for platinum-resistant ovarian cancer have low response rates of 15 to 20% and short median progression-free survival of three to four months,” noted Kathleen Moore, M.D., Associate Professor, Department of Obstetrics and Gynecology at the Stephenson Cancer Center at the University of Oklahoma.
“Based on the consistent safety and efficacy seen with mirvetuximab soravtansine reflected in these pooled analyses, particularly in those patients meeting the eligibility criteria for the pivotal study, I am very encouraged about the potential of this compound in patients with platinum-resistant ovarian cancer and look forward to continued progress with the ongoing Phase III FORWARD I trial,” Moore added.
For all 113 patients, the median number of prior regimens was 3, 85% had platinum-resistant disease, 67% had prior bevacizumab, and 22% had a prior poly (ADP-ribose) polymerase (PARP) inhibitor. The safety profile of the pooled population was consistent with data previously reported during the 2016 ASCO Annual Meeting, which consisted primarily of low grade, manageable adverse events. In this heavily pretreated group of patients, the confirmed ORR was 30% (95% CI 22, 39) and mPFS was 4.3 months (95% CI 3.9, 5.4).
Small molecule drug conjugates
Scientists at Endocyte will present two posters on the company’s lead, clinical-stage agents, EC1456 and EC1169.
The updated data on EC1456-01 comes from a two part phase I dose escalation (Part A) and expansion (Part B) study. The presentation includes data for 87 Part A treated patients with advanced solid tumors and 6 Part B treated patients with FR-positive non-small cell lung cancer (NSCLC) as of the data cutoff on May 18, 2017. In this trial, all patients were imaged to assess folate receptor expression with 99mTc-etarfolatide (FR expression not an eligibility criteria for Part A). Preliminary data from our first patient enrolled in the EC1456 ovarian surgical study, EC1456-02, will also be presented.
An update also will be provided for EC1169-01, a two-part phase I dose escalation (Part A) and expansion (Part B) study in patients with metastatic castration-resistant prostate cancer (mCRPC). The presentation includes data for the expansion phase (Part B) for 24 taxane-exposed mCRPC patients and 16 taxane-naïve mCRPC patients as of the data cutoff on May 15, 2017. All patients were imaged to assess PSMA expression with 99mTc-EC0652 (PSMA expression not an eligibility criteria).
This year, the objectives by the ASCO meeting’s organizers are to advance the education of physicians and other healthcare professionals caring for patients with cancer, to support the development of clinical cancer researchers and novel anti-cancer medications, and to facilitate the delivery of high-quality health care to patients with cancer. To meet this goal, the 2017 annual meeting is designed to serve the respective interests all – healthcare professionals and patients – with education focused on medical, surgical, and radiation oncology.
The abstracts for the 2017 annual meeting have been released earlier this month. While we’ve discussed some of the exciting updates, we believe that there is a lot more exciting information to be release during the upcoming meeting.