On June 4, 2018 Dynavax Technologies Corporation (NASDAQ:DVAX) reported data from its ongoing Phase 1b/2 study investigating SD-101, Dynavax’s intratumoral TLR9 agonist, in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy developed by Merck (known as MSD outside the United States and Canada) in patients with advanced melanoma (Press release, Dynavax Technologies, JUN 4, 2018, View Source [SID1234527166]).

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The company reported results on a total of 69 patients comparing two doses of SD-101, £ 2mg (n=30) versus 8mg (n=39) administered by intratumoral injection. These data are being presented in poster and discussion session today at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, in Chicago, IL. The primary endpoints of this dose-expansion/dose-finding study are safety and preliminary efficacy. The results of this study showed a 70% overall response rate (ORR) in advanced melanoma patients who received the £ 2 mg dose of SD-101 in up to four lesions versus a 38% ORR in the group receiving the 8 mg dose of SD-101 in one lesion. The combination of SD-101 and KEYTRUDA was well tolerated with adverse events related to SD-101 being transient, mild to moderate flu-like symptoms.

"These data provide further evidence of the potential for SD-101 to improve responses in first-line advanced melanoma patients in combination with an anti-PD-1 therapy," commented Eddie Gray, Chief Executive Officer. "Our studies continue to demonstrate the potential value of SD-101 across multiple tumor types. We plan to build upon this momentum and update our progress with additional data planned for a medical conference later in the year."

Highlights from Poster Presentation (Abstract #9513)

Overall response rate (ORR) of 70% (21 of 30), with a complete response (CR) rate of 17%, for advanced melanoma patients who received the £ 2 mg dose of SD-101 in up to four lesions

ORR of 38% (15 of 39) in patients who received the 8 mg dose of SD-101 in one lesion

Durable response in patients who received £ 2 mg dose of SD-101 with 74% 6-month progression free survival (PFS) rate

Observed responses in injected lesion(s) and distant lesions, including visceral metastases in the liver

Responders included 8 of 10 PD-L1 negative patients in the £ 2 mg dose cohort
AEs related to SD-101 treatment were transient, mild to moderate flu-like symptoms at both the £ 2mg and the 8 mg dosing levels

No increase in the frequency of immune-related adverse events over individual monotherapies reported in other studies1,2 nor evidence of any new safety signals
Additional details on response rates based on patient characteristics including stage of disease, ECOG score, and PD-L1 status are also included in the poster presentation which can be accessed here.

"We are moving forward with the 2mg dose of SD-101 for our Phase 3 trial which we believe is the optimal dose based on these efficacy, safety and biomarker data showing increased immune activation consistent with the biology of TLR9 activation. We continue to collect and analyze data from this trial to finalize details of the Phase 3 study design," stated Rob Janssen, Chief Medical Officer.

The details of the poster presentation and discussion session are as follows:

Phase 1b/2, open label, multicenter, study of the combination of SD-101 and pembrolizumab in patients with advanced melanoma who are naïve to anti-PD-1 therapy

Session Title: Melanoma/Skin Cancers

Abstract: 9513

Poster Board: 340

Poster Session Date/Time: Monday, June 4, 2018, 1:15 PM – 4:45 PM CDT

Poster Session Location: McCormick Place South, Hall A, Advanced Disease Poster Section

Discussion Session Date/Time: Monday, June 4, 2018, 4:45 PM – 6:00 PM CDT

Discussion Session Location: McCormick Place Lakeside Center, Level 4 – E451

Analyst/Investor Presentation

Today at 6:30pm CDT, Dynavax will host a presentation for analysts and investors. The presentation will be available via live webcast only and can be accessed in the "Investors and Media" section of the company’s website at www.dynavax.com.

About SYNERGY-001 (KEYNOTE-184)

SYNERGY-001, previously referred to as MEL-01, is the dose-escalation and expansion study of SD-101 in combination with KEYTRUDA which includes patients with histologically or cytologically confirmed unresectable Stage IIIC/IV melanoma. The primary endpoints of the trial are safety and preliminary efficacy of intratumoral SD-101 in combination with KEYTRUDA.

About SD-101

SD-101, the Company’s lead clinical candidate, is a proprietary, second-generation, Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. Dynavax is evaluating this intratumoral TLR9 agonist in several clinical studies to assess its safety and activity, including a Phase 2 study in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy, in patients with advanced melanoma and in patients with head and neck squamous cell cancer, in a clinical collaboration with Merck. Dynavax maintains all commercial rights to SD-101.

On June 4, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that encouraging new data from a Phase 1 study evaluating ivosidenib (AG-120) or enasidenib (IDHIFA; AG-221) in combination with azacitidine in newly diagnosed isocitrate dehydrogenase (IDH) mutant acute myeloid leukemia (AML) patients (Press release, Agios Pharmaceuticals, JUN 4, 2018, View Source [SID1234527119]). The data were featured at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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"Patients with newly diagnosed AML who are ineligible for intensive "7+3" chemotherapy typically have poor outcomes and few available treatment options," said Courtney DiNardo, M.D., lead investigator and assistant professor, department of leukemia at the University of Texas MD Anderson Cancer Center. "With additional patients now treated in the ivosidenib arm of this Phase 1 study, the updated combination data demonstrate a favorable safety profile and impressive response rates vs. those expected with azacitidine alone. I look forward to further demonstrating the clinical benefit of utilizing an IDH inhibitor in combination with traditional frontline AML treatment as part of the ongoing Phase 1 and randomized trials."

About the Ongoing Phase 1/2 Study
The ongoing Phase 1/2 study is evaluating an investigational use of enasidenib or ivosidenib in combination with azacitidine in patients with newly diagnosed IDH mutant AML unable to receive intensive chemotherapy. In the Phase 1b portion of the study, 23 patients received 500 mg of ivosidenib daily plus azacitidine and 6 patients received enasidenib (n=3 at 100 mg and n=3 at 200mg) daily plus azacitidine.

As of the March 15, 2018 data cutoff, 19 patients remained on study (17 ivosidenib, 2 enasidenib).
Enrollment is complete for the ivosidenib Phase 1b portion. Enasidenib and azacitidine continue to be assessed in the randomized Phase 2 portion of the study.
Ivosidenib Results
Safety

The most common adverse events (AEs) regardless of causality were nausea (61%, n=14), anemia (52%, n=12) and thrombocytopenia (48%, n=11).
The most common Grade 3-4 AEs were anemia and thrombocytopenia (44%, n=10 each), and febrile neutropenia (39%, n=9).
IDH differentiation syndrome was reported in three patients.
Efficacy

Overall, 78% of patients (18/23) had a response
The combined CR/CRi/CRp rate was 65% (15/23).

44% (10 of 23 patients) had a complete response (CR)
22% (5 of 23 patients) had a complete response with incomplete hematologic or platelet recovery (CRi/CRp)
All patients with a CR, CRi or CRp response remain on treatment as of the data cutoff with patients on study up to 19 months. The median duration of response has not been reach .
The median time to first response was 1.8 months (range 0.7-3.8 months) and the median time to best response was 3.6 months (range 0.8-6.7 months).
IDH1 mutation clearance was observed in 7 of 21 patients with available longitudinal VAF profiling

Enasidenib Results
Updated data from the six patients in the enasidenib and azacitidine combination presented in December 2017 were also shown.

Safety

The most common AEs regardless of causality were hyperbilirubinemia (n=5) and abdominal pain, nausea, vomiting and pyrexia (n=4 each).
The most common Grade 3-4 AEs were anemia and thrombocytopenia (n=3 each) followed by hyperbilirubinemia, neutropenia, lung infection and pneumonia (n=2 each).
Efficacy

Overall, four out of six patients achieved a response, including 3 CRs and one MLFS.
IDH2 mutation clearance was observed in 3 of 6 patients with available longitudinal VAF profiling
Neither enasidenib nor ivosidenib are approved in any country for the treatment of patients with newly diagnosed AML or approved in combination with azacitidine.

About Acute Myelogenous Leukemia (AML)
AML, a cancer of blood and bone marrow characterized by rapid disease progression, is the most common acute leukemia affecting adults. Undifferentiated blast cells proliferate in the bone marrow rather than mature into normal blood cells. AML incidence significantly increases with age, and the median age of diagnosis is 68. The vast majority of patients do not respond to chemotherapy and progress to relapsed/refractory AML. The five-year survival rate for AML is approximately 27 percent. IDH1 mutations are present in about 6 to 10 percent of AML cases.

On June 4, 2018 Castle Biosciences, Inc., the skin cancer diagnostics company providing molecular diagnostics to improve cancer treatment decisions, reported the presentation of data highlighting the accuracy and performance of the DecisionDx-Melanoma gene expression profile (GEP) test at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago, IL from June 1-5 (Press release, Castle Biosciences, JUN 4, 2018, View Source [SID1234527135]).

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The study titled, "Performance of a 31-gene expression profile melanoma test in clinically relevant clinicopathologic subgroups" (Abstract #9583), will be presented as a poster at the meeting. Results from the 690-patient study show that the DecisionDx-Melanoma test improved clinical risk prediction independent of traditional factors and consistent with findings from previous retrospective and prospective studies.

Key Study Findings:

Results from this multicenter study in 690 patients confirm that the DecisionDx-Melanoma test is an independent predictor of risk for recurrence, metastasis and melanoma-specific death, including clinically relevant subgroups.
The subgroup of American Joint Committee on Cancer (AJCC) Stage I-IIA patients who had a Class 2B result (highest risk) had significantly worse recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and melanoma-specific survival (MSS) rates compared to patients with a Class 1A result (lowest risk), important considerations that could impact surveillance and follow-up decisions.
For Stage IIIA patients, the DecisionDx-Melanoma test identified groups of patients with significantly different outcomes, which is increasingly important to inform decisions on adjuvant therapy and surveillance plans.
"Results from this multicenter study demonstrate that the GEP test can complement traditional AJCC staging factors by providing independent information that improves risk prediction for patients with melanoma," commented Brian Gastman, M.D., Cleveland Clinic Lerner Research Institute, Cleveland, Ohio. "With new options for patients increasing at a rapid pace, many clinical decisions are being made based on extrapolating data from different studies. Having additional, objective information is important to help patients and their treating physicians make definitive decisions, especially when there isn’t a clearly defined management plan."

Study Details:

Data from three previous DecisionDx-Melanoma validation studies were combined to enable analysis of clinically relevant subgroups. In this cumulative population of 690 Stage I-III patients, median age was 59 years, median time of follow-up was 6.5 years and median Breslow thickness was 1.3 mm. Seventy percent of patients had Stage I or II melanoma. The DecisionDx-Melanoma test was performed to determine molecular class for each patient, with a Class 1A result indicating the lowest 5-year risk of metastasis and a Class 2B result indicating the highest risk. Study endpoints included RFS (time to regional or distant metastatic event), DMFS (time to any metastatic event beyond the regional nodal basis) and MSS (time from diagnosis to death from melanoma).

Results confirm the prognostic accuracy of the DecisionDx-Melanoma test showing a significant difference among 5-year RFS rates for all groups. Patients with a Class 1A (lowest risk) result had an average RFS of 90% compared to 37% for Class 2B (highest risk) patients (p<0.0001). DMFS 5-year rates were 94% for Class 1A and 50% for Class 2B (p<0.0001). MSS 5-year rates were 99% for Class 1A and 75% for Class 2B (p<0.0001).

Based on Cox multivariate analysis in the Stage I-IIA subgroup, DecisionDx-Melanoma test class was found to be the only significant predictor of all three endpoints (RFS, DMFS and MSS; p<0.05 for all).

Additional Castle Biosciences Data at ASCO (Free ASCO Whitepaper) 2018

Preliminary data from the cutaneous squamous cell carcinoma (cSCC) development program will also be presented as a poster at the ASCO (Free ASCO Whitepaper) 2018 meeting (Abstract #9577). The study reports that preliminary gene expression based predictive models may offer important information about patient risk that builds on current staging methods. Results support the feasibility of the program to develop a clinically valuable test to predict which cSCC patients are at higher risk for local recurrence or regional/distant metastasis.

Additionally, an abstract highlighting the use of the DecisionDx-Melanoma test to identify a population of melanoma patients to assess risk of sentinel lymph node biopsy positivity (Abstract #e21611) will be included in the online ASCO (Free ASCO Whitepaper) 2018 proceedings.

About DecisionDx-Melanoma

The DecisionDx-Melanoma test uses tumor biology to predict individual risk of melanoma recurrence and sentinel lymph node positivity independent of traditional factors. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in three multi-center studies that have included 690 patients and have demonstrated consistent results. Performance has also been confirmed in four prospective studies including 702 patients. The consistent high performance and accuracy demonstrated in these studies, which combined have included over 1,300 patients, provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included over 1,400 patients. Clinical impact has been demonstrated in multi-center and single-center studies showing that test results impact clinical management decisions for one of every two patients tested. More information about the test and disease can be found at www.SkinMelanoma.com.

On June 4, 2018 Pfizer Inc. (NYSE:PFE) reported overall survival (OS) data from the ARCHER 1050 trial evaluating dacomitinib as a first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-activating mutations compared to gefitinib (Press release, Pfizer, JUN 4, 2018, View Source [SID1234527151]). The trial showed a median OS of 34.1 months for patients receiving dacomitinib (95% CI: 29.5, 37.7), representing a more than seven-month improvement compared to 26.8 months with gefitinib (95% CI: 23.7, 32.1). The OS data from ARCHER 1050 were presented today as an oral presentation [Abstract #9004] at the 54th Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago and have been published simultaneously in the Journal of Clinical Oncology.

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"Overall survival is an important measure to assess efficacy of investigational compounds. These data presented today are particularly significant as dacomitinib is the first EGFR tyrosine kinase inhibitor in a Phase 3 head-to-head study comparing two tyrosine kinase inhibitors to show an improvement in overall survival," said Professor Tony Mok, Chair of Department of Clinical Oncology, The Chinese University of Hong Kong. "I look forward to having dacomitinib as a potential first-line treatment option for non-small cell lung cancer patients with EGFR-activating mutations."

Overall survival was a secondary endpoint of ARCHER 1050, a randomized, open label Phase 3 study comparing the efficacy and safety of dacomitinib to gefitinib for the first-line treatment of locally advanced or metastatic NSCLC in subjects with EGFR-activating mutations. At the OS data cutoff, median OS was 34.1 months with dacomitinib (95% CI: 29.5, 37.7) compared to 26.8 months with gefitinib (95% CI: 23.7, 32.1). Patients receiving dacomitinib had a 56.2 percent survival rate at 30 months compared with 46.3 percent for patients who received gefitinib. Subgroup analyses were consistent with the primary OS analysis across most baseline characteristics, including patients with common sub-mutations exon 19 and 21.

The adverse events (AEs) observed with dacomitinib in the study were consistent with findings from previous dacomitinib trials. The most common AEs were diarrhea (87%), nail changes (62%), rash/dermatitis acneiform (49%) and mouth sores (44%). The most common Grade 3 AEs with dacomitinib were rash (14%) and diarrhea (8%). Grade 4 AEs occurred in two percent of dacomitinib-treated patients. There was one case of Grade 5 diarrhea and one case of Grade 5 liver disease. The discontinuation rate due to treatment-related AEs for dacomitinib was 10 percent compared to seven percent for gefitinib.

"What is most encouraging about these results is that patients with non-small cell lung cancer harboring EGFR-activating mutations who received dacomitinib achieved a median overall survival of nearly three years, a marked improvement compared to an established treatment in this setting," said Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global Product Development. "With today’s podium presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting and the U.S. Food and Drug Administration Priority Review granted earlier this year, we are encouraged by these data and committed to deliver this promising investigational medicine to patients as quickly as possible."

In April 2018, the U.S. Food and Drug Administration (FDA) granted priority review for dacomitinib for the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR-activating mutations. The FDA Prescription Drug User Fee Act (PDUFA) target action date is in September 2018. The European Medicines Agency also accepted the Marketing Authorization Application for dacomitinib for the same indication.

About Dacomitinib

Dacomitinib is an investigational, oral, once-daily, irreversible pan-human epidermal growth factor receptor tyrosine kinase inhibitor (TKI). It has not received regulatory approval in any country.

In 2012, Pfizer and SFJ Pharmaceuticals entered into a collaborative development agreement to conduct ARCHER 1050 across multiple sites.

About Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer deaths worldwide.1 Non-small cell lung cancer (NSCLC) accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.2 Biomarker therapies dramatically changed the care of patients with metastatic NSCLC. Approximately 75 percent of NSCLC patients are diagnosed late with metastatic or advanced disease where the five-year survival rate is only five percent.2,3,4

EGFR is a protein that helps cells grow and divide. When the EGFR protein is mutated it can cause cancer cells to form. EGFR mutations occur in 10 to 35 percent of NSCLC tumors globally, yet the disease is associated with low survival rates and disease progression remains a challenge.5,6

On June 4, 2018 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company") reported to confirm that it is involved in three poster presentations at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)‘s (ASCO) (Free ASCO Whitepaper) Annual Meeting, in Chicago, Illinois taking place from 1 – 5 June (Press release, Immutep, JUN 4, 2018, View Source [SID1234527167]). All three posters relate to Immutep’s lead product candidate eftilagimod alpha ("efti" or "IMP321").

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Two of the posters (TPS1050 and TPS1109), were presented on June 2, and focused on the Company’s Phase IIb AIPAC (Active Immunotherapy PAClitaxel) double blind placebo trial evaluating the efficacy of efti in patients with metastatic breast cancer.

The first poster discussed the results from the safety run-in phase of the AIPAC trial, which have been previously announced to the market. This poster was presented by Prof. Duhoux, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain. Specifically, it reiterated that the overall response rate ("ORR") in patients to the combination of paclitaxel and efti was 47%, and that the disease control rate ("DCR") was 87%. It also noted that two of the responses to the combination therapy occurred relatively late in the treatment (after ~6 months) and that the safety run-in phase reported a very encouraging safety profile.

The second poster, presented by Dr. Dirix of GZA Hospitals Sint-Augustinus, Antwerp, Belgium, outlined the ongoing AIPAC trial, its design and primary end points.

The third poster (TPS3129) outlines the clinical trial design of the ongoing INSIGHT clinical trial, an open-labeled Phase I study to evaluate the feasibility and safety of intra-tumoral, intra-peritoneal, and subcutaneous injections with efti for advanced stage solid tumors. This is an investigator sponsored trial by Immutep’s partner, IKF in Frankfurt, Germany, which will be presented by the investigator on June 5 in Chicago.

The ASCO (Free ASCO Whitepaper) posters regarding the Company’s AIPAC trial can be accessed via the Immutep website under the Presentations tab at:

View Source

About the AIPAC clinical trial

The ongoing AIPAC (Active Immunotherapy PAClitaxel) Phase IIb clinical trial is a European multi-centre study evaluating eftilagimod alpha ("efti" or "IMP321") in combination with paclitaxel in metastatic breast cancer (clinicaltrials.gov identifier NCT 02614833). To date, 33 out of a planned 34 clinical sites across Belgium, the Netherlands, Poland, Hungary, United Kingdom, France and Germany are now actively recruiting and treating patients. The AIPAC study is currently expected to be fully recruited with 226 patients by the end of calendar 2018, with first Progression Free Survival data expected in calendar 2019.

About the INSIGHT clinical trial

The on-going INSIGHT Phase I clinical trial is an investigator initiated, explorative, single centre, open-label, study evaluating the feasibility and safety of intra-tumoural, intra-peritoneal, and subcutaneous injections of efti for advanced stage solid tumour entities (clinicaltrials.gov identifier NCT03252938). The Lead Investigator of this clinical trial is Professor Doctor Salah-Eddin Al-Batran, the Medical Director of the IKF.