On June 26, 2017 ImmunoGen, Inc. (Nasdaq:IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported data from the ongoing Phase 1 study evaluating single agent IMGN779 in patients with relapsed or refractory adult acute myeloid leukemia (AML) whose tumors express CD33 (Press release, ImmunoGen, JUN 26, 2017, View Source [SID1234519685]). The first-in-human data demonstrate the safety and tolerability of IMGN779 across seven dose levels, with no dose limiting toxicities (DLTs), as well as evidence of dose-dependent biological and anti-leukemia activity. These results were presented in a poster presentation on Saturday, June 24, 2017, at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Madrid, Spain.

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IMGN779 combines a high-affinity, humanized anti-CD33 antibody with one of ImmunoGen’s novel indolino-benzodiazepine payloads, called IGNs, which alkylate DNA without crosslinking, resulting in potent anti-leukemia activity with relative sparing of normal hematopoietic progenitor cells.

Safety, pharmacokinetic (PK), and pharmacodynamic (PD) data, as well as initial anti-leukemia activity for IMGN779 through dose level seven were presented at EHA (Free EHA Whitepaper). Key findings included:

No DLTs have been observed through dose level seven, with reported adverse events consistent with the underlying disease.
No increase in the nature, frequency, or severity of any treatment-emergent adverse event has been reported with escalating doses and no evidence of cumulative toxicity has been observed with repeated dosing.
Favorable PK/PD reveal prolonged exposure and CD33 saturation at dose levels six and seven.
Initial anti-leukemia activity was observed at dose levels six and seven in patients who failed intensive frontline therapy.
The Phase 1 trial is designed to establish the maximum tolerated dose and determine the recommended Phase 2 dose for IMGN779 administered as monotherapy. The trial is also intended to evaluate safety and tolerability and characterize PK, PD, and preliminary anti-leukemia activity in relapsed or refractory AML. Dose escalation continues.

"We have designed our DNA-alkylating IGNs to be ultra-potent while providing the tolerability necessary for ongoing retreatment," said Richard Gregory, Ph.D., executive vice president and chief scientific officer of ImmunoGen. "We believe that by combining IGNs with our ADC technology, we may be able to treat a number of additional cancers that don’t respond to existing ADC therapies. These data suggest favorable tolerability and encouraging activity in patients with AML, and we look forward to determining the recommended dose for IMGN779 and moving quickly into later-stage development."

Preclinical data for IMGN779 were also presented at EHA (Free EHA Whitepaper) showing the agent is highly active in multiple AML xenograft models and is well-tolerated in preclinical repeat dosing regimens. Findings from the preclinical evaluation provided the foundation for the clinical evaluation of IMGN779 in AML.

Poster Details

Title: Initial results from a first-in-human study of IMGN779, a CD33-targeting antibody-drug conjugate (ADC) with novel DNA alkylating activity, in patients with relapsed or refractory AML
Abstract: P526

Title: Designing the next generation CD33-targeting ADC: IMGN779, selected for potency, novel mechanism and preclinical tolerability, with high activity in disseminated AML models and multi-dose regimens
Abstract: P562

Additional information – including the full abstracts – can be found at www.ehaweb.org.

About ImmunoGen, Inc.

ImmunoGen is a clinical-stage biotechnology company that develops targeted cancer therapeutics using its proprietary ADC technology. ImmunoGen’s lead product candidate, mirvetuximab soravtansine, is in a Phase 3 trial for FRα-positive platinum-resistant ovarian cancer, and is in Phase 1b/2 testing in combination regimens for earlier-stage disease. ImmunoGen’s ADC technology is used in Roche’s marketed product, Kadcyla, in three other clinical-stage ImmunoGen product candidates, and in programs in development by partners Amgen, Bayer, Biotest, CytomX, Debiopharm, Lilly, Novartis, Sanofi and Takeda. More information about the Company can be found at www.immunogen.com.

About Acute Myeloid Leukemia (AML)

AML is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal, immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems and anemia.

It is estimated that, in the U.S. alone, 20,000 patients will be diagnosed with AML this year and 10,000 patients will die from the disease.1 CD33 is expressed in virtually all cases of AML.

About IMGN779

IMGN779 is the first antibody drug conjugate (ADC) to utilize one of ImmunoGen’s new family of indolino-benzodiazepine cancer-killing agents known as IGNs. IMGN779 is comprised of a CD33-targeting antibody with a potent DNA-alkylating agent, the IGN DGN462, attached. The antibody serves to target the ADC to the CD33-positive AML cells which DGN462 can then kill. IMGN779 is wholly owned by ImmunoGen.

About IGNs

Indolino-benzodiazepine cancer-killing agents, or IGNs, are a new class of cancer-killing agent developed by ImmunoGen for use in ADCs. These ultra-potent, DNA-alkylating IGNs are expected to extend the types of cancers able to be effectively treated with ADC therapies beyond those addressable with ImmunoGen’s well-established tubulin-acting agents. Such cancers can include ones insensitive to tubulin-acting agents and/or with reduced antigen expression.

1American Cancer Society (2016), Leukemia – Acute Myeloid (Myelogenous) Detailed Guide.

This press release includes forward-looking statements. For these statements, ImmunoGen claims the protection of the safe harbor for forward-looking statements provided by the Private Securities Litigation Reform Act of 1995. It should be noted that there are risks and uncertainties related to the development of novel anticancer products, including IMGN779, including risks related to preclinical and clinical studies, their timings and results. A review of these risks can be found in ImmunoGen’s Annual Report on Form 10-K for the six-month transition period ended December 31, 2016 and other reports filed with the Securities and Exchange Commission.

On June 26, 2017 Epizyme, Inc. (NASDAQ:EPZM), a clinical-stage biopharmaceutical company creating novel epigenetic therapies, reported that it has expanded its clinical collaboration with Genentech, a member of the Roche Group (Press release, Epizyme, JUN 26, 2017, View Source [SID1234519684]). Under the new agreement, tazemetostat administered in combination with atezolizumab (TECENTRIQ) will be evaluated in a Phase 1b/2 clinical study for the treatment of patients with relapsed/refractory metastatic non-small cell lung cancer (NSCLC). The study will be part of MORPHEUS, Genentech’s open-label, multi-center, randomized umbrella study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations for metastatic NSCLC.

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"The MORPHEUS clinical platform is aimed at rapidly evaluating new cancer immunotherapy combination treatment regimens in patients with metastatic NSCLC," said Scott Clarke, global head, Roche oncology partnering. "The goal of this collaboration is to assess the role this combination therapy may play in immune-cell priming, activation and T-cell infiltration, potentially enhancing an anti-cancer response."

"A key part of Epizyme’s long-term vision is expanding the benefit that tazemetostat can bring to a broad range of patients, which includes evaluating tazemetostat in combination with a variety of anti-cancer agents, such as checkpoint inhibitors," said Robert Bazemore, president and chief executive officer of Epizyme. "NSCLC is a devastating form of lung cancer affecting nearly 200,000 people in the U.S. and major European countries. This study marks our second immuno-oncology combination with Genentech, and we look forward to working together to understand the benefit combination treatment with tazemetostat and atezolizumab may have for patients with this difficult cancer."

Genentech will sponsor the planned Phase 1b/2 clinical trial, which is expected to be initiated by the end of 2017. It is anticipated that the study will enroll up to 40 patients who have experienced disease progression during or following treatment with a platinum-containing chemotherapy regimen and a PD‑L1/PD-1 checkpoint inhibitor. Financial terms are not disclosed and Epizyme will retain global development and commercialization rights to tazemetostat.

Epizyme’s original collaboration with Genentech was announced in June 2016 to evaluate tazemetostat and atezolizumab as a combination regimen in a Phase 1b clinical trial for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma. That combination study is ongoing and continuing to enroll patients.

About the Tazemetostat Clinical Trial Program
Tazemetostat, a first-in-class EZH2 inhibitor, is currently being studied in ongoing Phase 2 programs in both follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) forms of non-Hodgkin lymphoma; certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors; and mesothelioma, as well as in combination studies in DLBCL. Tazemetostat has been granted Fast Track designation by the U.S. Food and Drug Administration for follicular lymphoma regardless of EZH2 mutation and for DLBCL with EZH2-activating mutations, as well as Orphan Drug designation for soft tissue sarcoma and malignant rhabdoid tumors.

On June 26, 2017 Sumitomo Dainippon Pharma Co., Ltd. (Head Office: Osaka, Japan; President: Masayo Tada) reported that the Company decided to unblind the BRIGHTER study, a phase 3 global study in patients with gastric and gastro-esophageal junction (GEJ) cancer of napabucasin (generic name, product code: BBI608), an investigational cancer stemness inhibitor, based on a recommendation by the study’s independent Data and Safety Monitoring Board (DSMB), following a pre-specified interim analysis (Press release, Dainippon Sumitomo Pharma, JUN 26, 2017, View Source [SID1234519683]).

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The study will be continued as an open label study to follow all endpoints as defined in the protocol.

The DSMB determined that the study was unlikely to reach its primary endpoint of superior overall survival for the napabucasin arm versus the control arm at the conclusion of the study. No safety concerns were identified by the DSMB.

Sumitomo Dainippon Pharma remains committed to other ongoing phase 3 studies (CanStem303C for colorectal cancer, CanStem111P for pancreatic cancer) with an aim to obtain marketing authorization of napabucasin as early as possible.

"Advanced gastric/GEJ cancer is a tumor type with high unmet need, and our hope was to develop a new therapeutic option for these patients. We are disappointed with the results of this interim analysis," said Patricia S. Andrews, Chief Executive Officer, Boston Biomedical, Inc. "We remain committed to our ongoing studies with napabucasin as well as our other first-in-class investigational compounds."

Sumitomo Dainippon Pharma is currently examining the effects that this matter will have on its consolidated business performance and will promptly make an announcement if it finds that there is a need to make further disclosures.

【About napabucasin】
Napabucasin is an investigational first-in-class anti-cancer agent created by Boston Biomedical, Inc., wholly-owned subsidiary of Sumitomo Dainippon Pharma. Napabucasin is an orally administered small molecule agent with a novel mechanism of action designed to inhibit cancer stemness pathways by targeting STAT3. Besides the gastric and GEJ cancer, napabucasin is currently being investigated in phase 3 studies for advanced colorectal and pancreatic cancer.


【About the BRIGHTER study】
The BRIGHTER study is a randomized, double blind global clinical phase 3 study to evaluate the efficacy and safety of administration of napabucasin plus weekly paclitaxel in comparison with weekly paclitaxel alone in the U.S., Japan and etc. A total of 714 patients with advanced gastric and GEJ cancer were previously treated with one prior line of platinum/fluoropyrimidine-containing regimen, randomized in a 1:1 ratio to receive napabucasin plus weekly paclitaxel or weekly paclitaxel alone. The primary endpoint is overall survival (OS) in the general study population; secondary endpoints include progression free survival (PFS), OS and PFS in a predefined biomarker-positive sub-population, objective response rate, disease control rate, and safety. The interim analysis of the BRIGHTER study was performed when the cumulative number of events reached 380.

On June 26, 2017 Bayer reported that the Ministry of Health, Labour and Welfare (MHLW) in Japan has granted marketing authorization for Stivarga (regorafenib) tablets for the second-line treatment of patients with unresectable hepatocellular carcinoma (HCC) who have progressed after treatment with cancer chemotherapy (Press release, Bayer, JUN 26, 2017, View Source [SID1234519682]). Stivarga, an oral inhibitor of multiple kinases involved in normal cellular functioning and in pathological processes such as oncogenesis, tumor angiogenesis, metastasis and tumor immunity, is the first and only treatment to demonstrate significant improvement in overall survival in second-line HCC patients who previously had no other options.

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"The number of patients suffering from liver cancer continues to increase in Japan and for years Nexavar was the first and only approved systemic treament option with proven overall survival benefit to help address this unmet need", said Robert LaCaze, Executive Vice President and Head of the Oncology Strategic Business Unit at Bayer. "The approval of Stivarga in Japan for second-line HCC is a significant step forward for patients and their treating doctors. For the first time, patients have a proven treatment plan involving Stivarga directly after Nexavar which could establish a new standard of care."

Since 1990, the annual mortality rate of liver cancer in Japan has increased by over 50%. Globally it is the second leading cause of cancer-related deaths.

The approval of Stivarga in HCC in Japan marks the third time that this therapy has been granted MHLW approval based on priority review, which is an expedited program given to medicines on the basis of their clinical usefulness and severity of the disease. The product is already approved in more than 90 countries worldwide for metastatic colorectal cancer (CRC), including Japan, and in more than 80 countries globally for the treatment of metastatic gastrointestinal stromal tumors (GIST), including Japan. Additional regulatory filings for Stivarga in HCC are under review in countries around the world and Stivarga in HCC has been approved by the FDA in the U.S.

The HCC approval is based on data from the international, multicenter, placebo-controlled Phase III RESORCE trial, which investigated patients with unresectable HCC whose disease had progressed during treatment with sorafenib. In the trial, regorafenib plus best supportive care (BSC) was shown to provide a statistically significant and clinically meaningful improvement in overall survival (OS) versus placebo plus BSC (HR 0.63; 95% CI 0.5-0.79; p<0.0001), which translates to a 37% reduction in the risk of death over the trial period.

The most common treatment-emergent adverse events (regorafenib vs. placebo group) were palmar-plantar erythrodysesthesia syndrome (53% vs. 8%), diarrhea (41% vs. 15%), fatigue (40% vs. 32%) and hypertension (31% vs. 6%).

About Hepatocellular Carcinoma
Hepatocellular carcinoma, or HCC, is the most common form of liver cancer and represents approximately 70-85 percent of liver cancer worldwide. Liver cancer is the sixth most common cancer in the world and the second leading cause of cancer-related deaths globally. More than 780,000 cases of liver cancer are diagnosed worldwide each year (52,000 in the European Union, 501,000 in the Western Pacific region and 30,000 in the United States) and the incidence rate is increasing. In 2012, approximately 746,000 people died of liver cancer including approximately 48,000 in the European Union, 477,000 in the Western Pacific region and 24,000 in the United States.

About Regorafenib (Stivarga)
Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R).

Regorafenib is approved under the brand name Stivarga in more than 90 countries worldwide, including the U.S., countries of the EU, China and Japan for the treatment of metastatic colorectal cancer (mCRC). The product is also approved in over 80 countries, including the U.S., countries of the EU, China and Japan, for the treatment of metastatic gastrointestinal stromal tumors (GIST). It was recently approved in the U.S. for second-line treatment of HCC and is now approved in Japan in this indication as well. Additional regulatory filings for Stivarga in HCC are under review in countries around the world, including the EU and China.

In the EU, Stivarga is indicated for the treatment of adult patients with mCRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy, as well as for the treatment of adult patients with unresectable or metastatic GIST who progressed on or are intolerant to prior treatment with imatinib and sunitinib.

Regorafenib is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx, now an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of regorafenib in oncology.