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Lilly Builds Upon Body of Data for Abemaciclib with Phase 3 MONARCH 2 Data Demonstrating Superior Progression-Free Survival in Advanced Breast Cancer

On June 3, 2017 Eli Lilly and Company (NYSE: LLY) reported that results from the Phase 3 MONARCH 2 study showed that abemaciclib, a cyclin-dependent kinase (CDK)4 & 6 inhibitor, in combination with fulvestrant, significantly improved progression-free survival (PFS) compared to treatment with fulvestrant alone in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer who have relapsed or progressed after endocrine therapy (median PFS, 16.4 vs. 9.3 months, respectively, HR: 0.553; 95% CI: 0.449, 0.681, P < .0000001) (Press release, Eli Lilly, JUN 3, 2017, View Source [SID1234519366]). The data were presented at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Abstract #1000) and simultaneously published online in the Journal of Clinical Oncology.

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"Metastatic HR+ breast cancer remains a dangerous disease and oncologists are always on the lookout for active new therapies to combat it," said George W. Sledge Jr., M.D., professor of medicine, Stanford University School of Medicine and principal investigator. "I am very impressed with the results from this study. For these patients who progressed on endocrine therapy, there was a significant prolongation of progression-free survival, and more than double the response rate, including an increased rate of complete response."

Patients with measureable disease treated with abemaciclib plus fulvestrant achieved an objective response rate (ORR) of 48.1 percent (3.5% complete response [CR]), compared to 21.3 percent (0% CR) in patients treated with fulvestrant alone. Additionally, abemaciclib plus fulvestrant caused a greater degree of tumor shrinkage than fulvestrant alone.

"One of our goals with the MONARCH clinical development program is not to replicate studies, but rather to further innovate in the field of CDK4 & 6 inhibition and advance potential treatment options for patients wherever they may be in the course of their disease," said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology. "From the single-agent activity seen in MONARCH 1 to the significant MONARCH 2 results shared today, and our ongoing Phase 3 studies, we are committed to working with physicians to evolve treatment expectations for people living with breast cancer."

The global Phase 3, double-blind study was designed to evaluate the efficacy and safety of abemaciclib, in combination with fulvestrant, in patients with advanced (locoregionally recurrent or metastatic) breast cancer. The intent-to-treat population of 669 patients was randomized to receive abemaciclib or placebo orally twice a day on a continuous dosing schedule, given in combination with fulvestrant at its approved dose and schedule, until disease progression. Patients enrolled in the study had experienced disease progression on or within 12 months of receiving endocrine treatment in the neoadjuvant or adjuvant setting or while receiving first-line endocrine therapy for metastatic disease. Patients who had received chemotherapy in the metastatic setting were not eligible for the study. The primary endpoint for MONARCH 2 was PFS.

The most frequent adverse events (AEs) of any grade in the abemaciclib plus fulvestrant arm were diarrhea, neutropenia, nausea, and fatigue. Of these, the reported Grade 3 AEs (abemaciclib vs. placebo arm) were diarrhea (13.4% vs. 0.4%), neutropenia (23.6% vs. 1.3%), nausea (2.7% vs. 0.9%), and fatigue (2.7% vs. 0.4%). No patients in either arm experienced Grade 4 diarrhea, nausea or fatigue, and Grade 4 neutropenia was observed in 2.9 percent versus 0.4 percent of patients in the abemaciclib versus placebo arms, respectively.

Severity and frequency of diarrhea generally decreased following one to two cycles, and was managed with loperamide or dose reduction. The majority (70.1%) of patients in the abemaciclib arm with an AE of diarrhea did not require treatment modification (dose interruption, reduction, or discontinuation), and 2.9 percent of patients discontinued the study drug due to diarrhea.

In addition to the ongoing MONARCH trials, including the newly initiated monarchE adjuvant study, which will assess abemaciclib in patients with high-risk, early breast cancer, Lilly is actively evaluating abemaciclib in lung cancer, pancreatic cancer, and patients with brain metastases.

Notes to Editor

About Advanced Breast Cancer
Breast cancer is the most common cancer in women worldwide with nearly 1.7 million new cases diagnosed in 2012.[1] Advanced breast cancer includes metastatic breast cancer, cancer that has spread from the breast tissue to other parts of the body, and locally or regionally advanced breast cancer, meaning the cancer has grown outside the organ where it started but has not yet spread to other parts of the body.[2] Of all early stage breast cancer cases diagnosed in the U.S., approximately 30 percent will become metastatic and an estimated six to 10 percent of all new breast cancer cases are initially diagnosed as being metastatic.[3] Survival is lower among women with a more advanced stage at diagnosis: 5-year relative survival is 99 percent for localized disease, 85 percent for regional disease, and 26 percent for metastatic disease. Other factors, such as tumor size, also impact 5-year survival estimates.[4]

About Abemaciclib
In many cancers, uncontrolled cell growth arises from a loss of cell cycle regulation due to increased signaling from CDK4 and CDK6. Abemaciclib (LY2835219) is an investigational, oral cell cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting cyclin-dependent kinases, CDK4 and CDK6, and was most active against Cyclin D1 and CDK4 in cell-free enzymatic assays. In breast cancer, Cyclin D1/CDK4 has been shown to promote phosphorylation of the retinoblastoma protein (Rb), cell proliferation and tumor growth. In hormone receptor-positive breast cancer cell lines, sustained target inhibition by abemaciclib reduced phosphorylation of Rb, inducing cell cycle arrest.

In 2015, the U.S. Food and Drug Administration granted abemaciclib Breakthrough Therapy Designation based on data from the breast cancer cohort expansion of the company’s Phase 1 trial, JPBA, which studied the efficacy and safety of abemaciclib in women with advanced or metastatic breast cancer. In addition to its current MONARCH clinical trials evaluating abemaciclib in breast cancer, a Phase 3 trial of abemaciclib in lung cancer is also underway.

For more information on additional abemaciclib trials, a complete listing can be found on ClinicalTrials.gov (in the search box on the home page, type in "abemaciclib").

About the MONARCH Clinical Trial Program
Lilly is evaluating abemaciclib in the comprehensive MONARCH clinical program, which includes the following studies:

MONARCH 1: a global Phase 2 study evaluating the efficacy and safety of abemaciclib monotherapy in patients with HR+, HER2- advanced breast cancer who had prior endocrine therapy and chemotherapy for metastatic disease.

MONARCH 2: a global Phase 3 study evaluating the efficacy and safety of abemaciclib, in combination with fulvestrant, in patients with HR+, HER2- advanced breast cancer who progressed on endocrine therapy.

MONARCH 3: a global Phase 3 study evaluating the efficacy and safety of abemaciclib, in combination with an aromatase inhibitor, as initial endocrine-based therapy for postmenopausal women with HR+, HER2- advanced breast cancer who have had no prior systemic treatment for advanced disease.

monarcHER: a global Phase 2 study evaluating abemaciclib plus trastuzumab (with or without fulvestrant) in women with HR+, HER2+ advanced breast cancer.

MONARCH plus: a Phase 3 study evaluating the efficacy and safety of abemaciclib, in combination with endocrine therapies, to support registration in China.

neoMONARCH: a Phase 2 study evaluating abemaciclib in the neoadjuvant setting, alone or in combination with the non-steroidal aromatase-inhibitor anastrozole, in postmenopausal women with previously untreated early stage HR+, HER2- breast cancer.

monarchE: a global Phase 3 study evaluating the efficacy and safety of abemaciclib in the adjuvant setting in patients with high-risk, early breast cancer.

Amgen Presents New Phase 2 Data On IMLYGIC® (Talimogene Laherparepvec) Investigational Combination At ASCO 2017

On June 3, 2017 Amgen (NASDAQ:AMGN) reported new data from the Phase 2 ‘264 study that demonstrated IMLYGIC (talimogene laherparepvec) in combination with the immune checkpoint inhibitor YERVOY (ipilimumab)* more than doubled objective response rate (ORR), defined as the proportion of patients with tumor size reduction, compared to YERVOY alone in patients with unresectable stage IIIB-IV melanoma, meeting the primary endpoint of the study (Press release, Amgen, JUN 3, 2017, View Source [SID1234519359]).

The analysis showed that 38.8 percent of patients treated with IMLYGIC plus YERVOY achieved an objective response versus 18 percent of patients treated with YERVOY alone (odds ratio=2.9, 95 percent CI: 1.5, 5.5; p=0.002). Patients in the combination arm also experienced nearly double the complete response rate compared to YERVOY alone (13.3 percent versus 7 percent). The results were presented at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper).

"Metastatic melanoma continues to be one of the most difficult-to-treat and aggressive cancers," said Jason Chesney, M.D., ‘264 study investigator and acting director of the James Graham Brown Cancer Center, University of Louisville, Louisville, Ky. "The results from this study demonstrate the potential of combining the complementary mechanisms of action of an oncolytic viral immunotherapy and a checkpoint inhibitor to enhance anti-tumor effect in patients with advanced melanoma."

Responses were not limited to injected lesions. Among patients with visceral disease treated with IMLYGIC plus YERVOY, 35 percent had a reduction in size of visceral lesions by at least 50 percent. The rate was 14 percent in patients in the YERVOY arm. Patients in the IMLYGIC plus YERVOY arm experienced a median progression-free survival (PFS) of 8.2 months (median follow up 68 weeks) versus 6.4 months in the YERVOY arm. The effect was not statistically significant (HR=0.83, 95 percent CI; p=0.35); however, the PFS analysis was not event-driven and is still ongoing, with only approximately 50 percent of PFS events reported at this time.

"Patients with metastatic melanoma are in need of innovative, effective treatment options that can improve response rates and help prevent disease recurrence," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "These are the first randomized, controlled, Phase 2 data demonstrating clear efficacy and safety of an oncolytic virus with a checkpoint inhibitor. We are excited to be exploring IMLYGIC with PD-1 and PDL-1 checkpoint inhibitors as well."

The most common adverse events in the IMLYGIC plus YERVOY arm were fatigue (59 percent versus 42 percent, respectively), chills (53 percent versus 3 percent, respectively) and diarrhea (42 percent versus 35 percent, respectively). Evaluation of overall survival (OS) is ongoing and continues to be monitored. IMLYGIC is designed to rupture cancer cells causing the release of tumor-derived antigens, which along with granulocyte-macrophage colony-stimulating factor (GM-CSF), may help to initiate an anti-tumor immune response. However, the exact mechanism of action is unknown. This may be complementary to YERVOY’s mechanism of action, as the blockade of cytotoxic T-lymphocyte-associated antigen-4 has been shown to augment activation and proliferation of tumor infiltrating T-effector cells.

In addition, these results follow the presentation of new interim data from a Phase 2 biomarker study, which evaluated CD8+ T cell density in biopsies from patients with unresectable stage IIIB-IVM1c melanoma treated with IMLYGIC. These data were presented at the 13th Congress of the European Association of Dermato Oncology in Athens, Greece. The study demonstrated a significant four-fold mean increase in intratumoral CD8+ cell density in uninjected melanoma lesions among 32 matched biopsy pairs collected at baseline and after two doses of IMLYGIC. The response rate was consistent with other IMLYGIC monotherapy studies and the adverse events profile was consistent with the known safety profile of IMLYGIC.

About the ‘264 Study
The ‘264 study is a Phase 1b/2, multicenter, open-label trial evaluating the safety and efficacy of IMLYGIC in combination with YERVOY compared to YERVOY alone in patients with unresectable stage IIIB-IV melanoma. The primary endpoint of the Phase 2 portion of study is ORR. Secondary endpoints include duration of response, disease control rate, PFS, OS and safety. The study randomized 198 patients, 98 in the IMLYGIC plus YERVOY arm and 100 in the YERVOY arm.

About Metastatic Melanoma
Melanoma remains a significant public health concern across the globe. Unlike some other cancers, melanoma incidence rates have doubled in the past 40 years, with 132,000 cases occurring worldwide each year.1,2 Melanoma is more dangerous than other skin cancers, especially when it spreads to other parts of the body, which is referred to as metastatic disease.3 The overall five-year risk of relapse after surgery increases as disease stage advances, from 48 percent for stage IIIA to 85 percent for stage IIIC.4 Risk of recurrence is even higher for patients in stage IV undergoing surgery, with 91 percent experiencing relapse.5 Despite new options, additional treatments are needed – particularly for patients with metastatic disease.

About IMLYGIC (talimogene laherparepvec)
IMLYGIC (talimogene laherparepvec) is a genetically modified herpes simplex type 1 virus that is injected directly into tumors. IMLYGIC replicates inside tumor cells and produces GM-CSF, an immunostimulatory protein. IMLYGIC then causes the cell to rupture and die in a process called lysis. The rupture of the cancer cells causes the release of tumor-derived antigens, which together with virally derived GM-CSF may help to promote an anti-tumor immune response. However, the exact mechanism of action is unknown.

IMLYGIC is the first oncolytic viral therapy approved by the U.S. Food and Drug Administration (FDA) based on therapeutic benefit demonstrated in a pivotal study. IMLYGIC is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery. IMLYGIC has not been shown to improve OS or have an effect on visceral metastases.

Important U.S. Safety Information

Contraindications

Do not administer IMLYGIC to immunocompromised patients, including those with a history of primary or acquired immunodeficient states, leukemia, lymphoma, AIDS or other clinical manifestations of infection with human immunodeficiency viruses, and those on immunosuppressive therapy, due to the risk of life-threatening disseminated herpetic infection.
Do not administer IMLYGIC to pregnant patients.
Warnings and Precautions

Accidental exposure to IMLYGIC may lead to transmission of IMLYGIC and herpetic infection, including during preparation and administration. Health care providers, close contacts, pregnant women, and newborns should avoid direct contact with injected lesions, dressings, or body fluids of treated patients. The affected area in exposed individuals should be cleaned thoroughly with soap and water and/or a disinfectant.
Caregivers should wear protective gloves when assisting patients in applying or changing occlusive dressings and observe safety precautions for disposal of used dressings, gloves, and cleaning materials. Exposed individuals should clean the affected area thoroughly with soap and water and/or a disinfectant.
To prevent possible inadvertent transfer of IMLYGIC to other areas of the body, patients should be advised to avoid touching or scratching injection sites or occlusive dressings.
Herpetic infections: Herpetic infections (including cold sores and herpetic keratitis) have been reported in IMLYGIC-treated patients. Disseminated herpetic infection may also occur in immunocompromised patients. Patients who develop suspicious herpes-like lesions should follow standard hygienic practices to prevent viral transmission.
Patients or close contacts with suspected signs or symptoms of a herpetic infection should contact their health care provider to evaluate the lesions. Suspected herpetic lesions should be reported to Amgen at 1-855-IMLYGIC (1-855-465-9442). Patients or close contacts have the option of follow-up testing for further characterization of the infection.
IMLYGIC is sensitive to acyclovir. Acyclovir or other antiviral agents may interfere with the effectiveness of IMLYGIC. Consider the risks and benefits of IMLYGIC treatment before administering antiviral agents to manage herpetic infection.
Injection Site Complications: Necrosis or ulceration of tumor tissue may occur during IMLYGIC treatment. Cellulitis and systemic bacterial infection have been reported in clinical studies. Careful wound care and infection precautions are recommended, particularly if tissue necrosis results in open wounds.
Impaired healing at the injection site has been reported. IMLYGIC may increase the risk of impaired healing in patients with underlying risk factors (e.g., previous radiation at the injection site or lesions in poorly vascularized areas). If there is persistent infection or delayed healing of the injection site, consider the risks and benefits of continuing treatment.
Immune-Mediated events including glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis, and vitiligo have been reported in patients treated with IMLYGIC. Consider the risks and benefits of IMLYGIC before initiating treatment in patients who have underlying autoimmune disease or before continuing treatment in patients who develop immune-mediated events.
Plasmacytoma at the Injection Site: Plasmacytoma in proximity to the injection site has been reported in a patient with smoldering multiple myeloma after IMLYGIC administration in a clinical study. Consider the risks and benefits of IMLYGIC in patients with multiple myeloma or in whom plasmacytoma develops during treatment.
Obstructive Airway Disorder: Obstructive airway disorder has been reported following IMLYGIC treatment. Use caution when injecting lesions close to major airways.
Adverse Reactions

The most commonly reported adverse drug reactions (≥ 25%) in IMLYGIC-treated patients were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain. Pyrexia, chills, and influenza-like illness can occur at any time during IMLYGIC treatment, but were more frequent during the first 3 months of treatment.
The most common Grade 3 or higher adverse reaction was cellulitis.
Please see full Prescribing Information and Medication Guide for IMLYGIC.

Agios Presents Phase 1 Data from Dose-Escalation and Expansion Cohorts of AG-120 (Ivosidenib) in Patients with Previously Treated IDH1 Mutant Positive Cholangiocarcinoma

On June 3, 2017 Agios Pharmaceuticals, Inc. (Nasdaq:AGIO), a leader in the fields of cancer metabolism and rare genetic diseases,reported updated data from the dose-escalation and expansion cohorts of the Phase 1 study evaluating single agent AG-120 (ivosidenib) in isocitrate dehydrogenase-1 (IDH1) mutant positive cholangiocarcinoma at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 2-6, 2017 in Chicago (Press release, Agios Pharmaceuticals, JUN 3, 2017, View Source [SID1234519357]).

"The durable disease control signal seen with the Phase 1 data, combined with AG-120’s favorable safety profile, are encouraging for patients with advanced IDH1 mutant cholangiocarcinoma who have received multiple prior therapies," said Maeve Lowery, M.D., Memorial Sloan Kettering Cancer Center who presented the study results. "With no approved treatments and few effective options beyond the first line setting in this challenging disease, we look forward to continuing to characterize AG-120’s activity in the Phase 3 ClarIDHy study."

"Consistent with AG-120’s unique mechanism of action and in the context of this heavily pre-treated patient population, we believe durable stable disease is a meaningful measure of clinical benefit," said Chris Bowden, M.D., chief medical officer at Agios. "These data support further development of AG-120 in our ongoing Phase 3 registration-enabling ClarIDHy study, where we aim to confirm the early efficacy signal and evaluate the potential to impact tumor biology."

The ongoing Phase 1 trial is assessing the safety and tolerability of AG-120 in advanced solid tumors, including glioma, cholangiocarcinoma and chondrosarcomas with an IDH1 mutation. Enrollment is now complete for the dose-escalation and expansion cohorts. As of March 10, 2017, 73 patients with IDH1 mutant positive cholangiocarcinoma have been treated with single agent AG-120 in the dose escalation (n=24) and expansion cohorts (n=49). Thirteen patients remain on treatment. AG-120 was administered at the following dose levels and schedules in the dose-escalation cohort: 100 mg twice daily, and 300, 400, 500, 800 and 1200 mg once a day over a 28 day cycle length. In the dose expansion cohort, patients received 500 mg once a day, which was the selected dose for the ongoing Phase 3 ClarIDHy trial. Among the Phase 1 cholangiocarcinoma population, the median age is 60 (ranging from 32-81). Sixty-five patients had intrahepatic cholangiocarcinoma and eight had extrahepatic disease. The median number of prior systemic therapies was two (ranging from one to five) and 97% of patients received a prior gemcitabine-based chemotherapy regimen.

Safety Data

A safety analysis conducted for all 73 treated patients as of the data cut-off demonstrated that AG-120 was well-tolerated with a favorable safety profile in IDH1 mutant positive cholangiocarcinoma patients.

No dose limiting toxicities or treatment-related deaths have been observed.
The majority of adverse events (AEs) reported were mild to moderate, with the most common regardless of causality being fatigue, nausea, diarrhea and decreased appetite.
Four patients experienced drug-related AEs ≥ grade 3: two at the 500 mg dose level, fatigue (n=1) and blood alkaline phosphatase increases (n=1) and two at the 1200 mg dose level, fatigue (n=1) and blood phosphorous decreases (n=1).
One patient had a dose reduction for a grade 2 AE of worsening leg cramps that was considered to be possibly drug-related.
Efficacy Data

Efficacy data from all 73 treated patients as of the data cut-off showed:

Four patients (5%) experienced a confirmed partial response (one at 300 mg QD and three at 500 mg QD). A partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Forty-one patients (56%) experienced stable disease.
Landmark analyses of progression free survival at six (PFS6) and 12 months (PFS12) were 38.5% and 20.7% respectively. The median progression free survival (PFS) was 3.8 months (95% CI 3.6, 7.3).
AG-120 treatment inhibited plasma 2-hydroxyglutarate (2-HG) to within levels found in healthy volunteers, and also reduced 2-HG in tumor biopsies, with 2-HG levels in plasma and tumor biopsies showing a positive correlation.
Pathology review of on-study tumor biopsies were conducted in a patient achieving a partial response, which showed morphologic changes suggestive of cellular differentiation which is consistent with the proposed mechanism of action of AG-120.
ClarIDHy Phase 3 Trial

AG-120 (ivosidenib) is currently being evaluated in an ongoing, global, registration-enabling randomized Phase 3 trial known as ClarIDHy, enrolling 186 previously treated IDH1m positive cholangiocarcinoma patients who have documented disease progression following one or two systemic therapies in the advanced setting.

Patients will be randomized 2:1 to receive either single-agent AG-120 500 mg once daily or placebo with crossover to AG-120 permitted at the time of progression.
The primary endpoint of the trial is PFS with secondary endpoints including safety and tolerability, overall response rate, overall survival, duration of response, PK/PD and quality of life assessments.
Assuming a median PFS of 3 months for the control group, the study was designed with 96% power to detect a hazard ratio of 0.5 for PFS (AG-120 vs placebo), with a one-sided alpha of 0.025.
Thermo Fisher Scientific is providing next-generation sequencing to detect IDH1m for all tumor samples as inclusion criteria for enrollment in the study and will develop and commercialize the validated companion diagnostic.
About Cholangiocarcinoma

Cholangiocarcinoma (CC) is a rare cancer of the bile ducts within and outside of the liver. Cases that occur within the liver are known as intrahepatic cholangiocarcinoma (IHCC) and those that occur outside the liver are considered extrahepatic. Mutations in IDH1 occur in 13–15% of CC cases overall and in up to 25% of IHCC cases. Current treatment options for localized disease include surgery, radiation and/or other ablative treatments. There are no approved systemic therapies for cholangiocarcinoma and limited chemotherapy options are available in the advanced setting. Gemcitabine-based chemotherapy is often recommended for newly diagnosed metastatic disease. Progression-free survival (PFS) in patients with advanced biliary cancer receiving second-line chemotherapy is 2–3 months.

Dynavax Presents Updated Data for SD-101 in Combination with KEYTRUDA® (pembrolizumab) Highlighting an ORR in 7 out of 7 Patients Naïve to an Anti-PD-1 or Anti-PD-L1 Therapy

On June 2, 2017 Dynavax Technologies Corporation (NASDAQ: DVAX) reported the presentation of findings in patients with metastatic melanoma in the dose escalation phase of an 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 (Press release, Dynavax Technologies, JUN 2, 2017, View Source [SID1234519437]). Results evaluating 19 patients for efficacy and 22 patients for safety were presented in a poster at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago:

• In 7 anti-PD-1/L1-naïve patients, SD-101 used in combination with KEYTRUDA resulted in an overall response rate (ORR) of 100%, with a complete response (CR) rate of 29%. This is a meaningful increase over use of KEYTRUDA alone, which has already shown a 33% ORR, with a 6% CR.1

• In 12 patients with advanced (stage IIIc/IV) melanoma who had previously failed on anti-PD-1 treatment, introduction of SD-101 resulted in tumor shrinkage in 42% of patients, with 17% having a partial response (PR), indicating an anti-tumor immune response generated by SD-101.

• The combination of SD-101 and KEYTRUDA in this study, mobilized both innate and adaptive immune response in study participants.

• Tumor shrinkage was observed in non-injected visceral lesions.

"Having 7 out of 7 patients naïve to anti-PD-1/L1 treatment responding is very encouraging," said Antoni Ribas, M.D., Ph.D., of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, and lead investigator. "These results are supported by tumor shrinkage in patients who had previously progressed on anti-PD-1 treatment and by confirmatory laboratory biomarker assessments in tumor biopsies. If these clinical results are sustained in the ongoing trial, this combination, which mobilizes both innate and adaptive immune responses in patients, could represent an important advancement in immuno-oncology."

SD-101 in combination with KEYTRUDA generally was well-tolerated. No dose-limiting toxicities of the combination were observed in any dose cohort, and a maximum tolerated dose (MTD) was not identified. The most common treatment-emergent adverse events were injection site reactions and transient grade 1 to 2 flu-like symptoms, including fever, chills and myalgia. The study also includes biomarker assessments, suggesting that treatment with SD-101 and KEYTRUDA resulted in increased tumor-infiltrating lymphocytes and decreased Th2 in tumor biopsies, consistent with induction of an antitumor immune response.

Keytruda.com View Source

About MEL-01 (KEYNOTE-184)
The dose-escalation and expansion study of SD-101 in combination with KEYTRUDA includes patients with histologically or cytologically confirmed unresectable Stage IIIc/IV melanoma. The primary endpoints of the trial are MTD and evaluation of the safety of intratumoral SD-101 in combination with KEYTRUDA. In addition, the trial is investigating response as assessed by the investigator according to RECIST v1.1, biomarker assessments and duration of response. Patients previously treated with anti-PD-1 and other immunotherapies are included.

About SD-101
SD-101 is Dynavax’s proprietary, second-generation, Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. SD-101 is being studied for its multiple anti-tumor activities in innate immune cells and activation of plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. TLR9 agonists such as SD-101 enhance T and B cell responses and provide potent Type 1 interferon induction and maturation of plasmacytoid dendritic cells to antigen-presenting cells. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its safety and activity.

For information about SD-101 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.

Results from Clinical Trial of Indoximod Plus Chemotherapy for Patients with Metastatic Breast Cancer

On June 2, 2017 NewLink Genetics Corporation (NASDAQ:NLNK) reported the results from a Phase 2 trial of indoximod in combination with taxane chemotherapy for patients with metastatic breast cancer (Press release, NewLink Genetics, JUN 2, 2017, View Source [SID1234519388]).

Top line data from the study show that the trial did not meet its pre-specified endpoints of a statistically significant difference between the two treatment groups as to progression-free survival, overall survival or objective response rate.

"As demonstrated by multiple studies that have been reported since the start of this clinical trial, breast cancer unfortunately remains a challenging disease in immuno-oncology," said Primary Investigator Hatem Soliman MD, Associate Member Breast, Tumor Biology, and Immunology Departments, Chair Clinical Research Advisory Committee, H. Lee Moffitt Cancer Center and Research Institute, Associate Professor, Division of Oncologic Sciences University of South Florida.

In this study, NLG2101, 169 first line metastatic breast cancer patients were selected to receive either docetaxel or paclitaxel by their treating physicians. Once the choice of backbone chemotherapy was made, patients were then randomized to receive either indoximod or placebo.

"We would like to thank all the patients, families, investigators, and research teams who supported the completion of this trial," said Charles J. Link, Jr., M.D., Chairman and CEO of NewLink Genetics. "Independent of these results, we continue to be highly encouraged by indoximod as an IDO pathway inhibitor and look forward to future opportunities to share data from ongoing trials in multiple cancer types including melanoma, prostate cancer, acute myelogenous leukemia, and pancreatic cancer."

Full results of the trial will be presented at an upcoming academic meeting.