On June 5, 2017 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that results from its pivotal Phase III trial with fruquintinib, its novel vascular endothelial growth factor receptor ("VEGFR") kinase inhibitor, were highlighted in an oral presentation today during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting ("ASCO"), held in Chicago (Press release, Hutchison China MediTech, JUN 5, 2017, http://www.chi-med.com/highlights-fruquintinib-ph3-data-at-asco/ [SID1234519422]). Results showed that FRESCO, a randomized, double-blind, placebo-controlled, multi-centered Phase III trial assessing fruquintinib in patients with locally advanced or metastatic colorectal cancer ("CRC") in China, met all primary and secondary endpoints including significant improvements in overall and progression-free survival with a manageable safety profile and lower off-target toxicities compared to other targeted therapies.

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"Data from this 416-patient trial showed that treatment with fruquintinib resulted in statistically significant and clinically meaningful survival benefits in colorectal cancer patients who failed two previous lines of systemic therapy," said Dr. Jin Li, Director of the Department of Oncology, Tongji University affiliated Shanghai East Hospital. "Importantly, adverse events associated with fruquintinib therapy were manageable and controllable. Particularly encouraging was that fruquintinib showed relatively low frequency and less severe liver function abnormalities as compared with other targeted therapies used in this disease setting."

"The totality of safety and efficacy data suggest fruquintinib can be an important new treatment option for patients whose colorectal cancer continues to progress," he concluded.

Efficacy Results

The FRESCO trial is a randomized, double-blind, placebo-controlled, multicenter, Phase III pivotal trial in patients with locally advanced or metastatic CRC who have failed at least two prior systemic antineoplastic therapies, including fluoropyrimidine, oxaliplatin and irinotecan. No drugs have been approved in third-line CRC in China, with best supportive care ("BSC") being the general standard of care. Enrollment was completed in May 2016. 519 patients were screened. The intention-to-treat (ITT) population of 416 patients was randomized at a 2:1 ratio to receive either: 5mg of fruquintinib orally once per day, on a three-weeks-on / one-week-off cycle, plus BSC (278 patients); or placebo plus BSC (138 patients). Randomization was stratified for prior anti-VEGF therapy and K-Ras gene status. The trial was concluded on January 17, 2017.

The primary endpoint of median overall survival (OS) was 9.30 months [95% CI 8.18–10.45] in the fruquintinib group vs. 6.57 months [95% CI 5.88–8.11] in the placebo group, with a hazard ratio of 0.65 [95% CI: 0.51–0.83; two-sided p<0.001].

The secondary endpoint of median progression-free survival (PFS) was 3.71 months [95% CI 3.65–4.63] in the fruquintinib group vs. 1.84 months [95% CI 1.81–1.84] in the placebo group, with a hazard ratio of 0.26 [95% CI: 0.21–0.34; two-sided p<0.001].

Significant benefits were also seen in other secondary endpoints. The fruquintinib group disease control rate (DCR) was 62.2% vs. 12.3% for placebo (p<0.001), while the overall response rate (ORR) was 4.7% vs. 0% for placebo (p=0.012).



Safety and Tolerability Results

Results showed that fruquintinib had a manageable safety profile with lower off-target toxicities compared to other targeted therapies, and did not demonstrate the sometimes severe and fatal hepatotoxicity (liver toxicity) observed with other therapies in this disease setting. The most frequently reported fruquintinib-related grade ≥3 adverse events included hypertension (21.2%), hand-foot skin reaction (10.8%), proteinuria (3.2%) and diarrhea (2.9%), all associated with VEGFR inhibition. No other grade ≥3 adverse events exceeded 1.4% in the fruquintinib population, including hepatic function adverse events such as elevations in bilirubin (1.4%), alanine aminotransferase (ALT) (0.7%) or aspartate aminotransferase (AST) (0.4%).

Dose interruptions or reductions occurred in only 35.3% and 24.1% of patients in the fruquintinib arm, respectively, and only 15.1% of patients discontinued treatment vs. 5.8% for placebo.

The FRESCO study may be found at clinicaltrials.gov using identifier NCT02314819. The presentation will be available at chi-med.com/wp-content/uploads/2017/06/pre170605-013asco.pdf.

Chi-Med expects to complete the New Drug Application (NDA) submission for fruquintinib to the China Food and Drug Administration imminently. The Company also expects to initiate U.S. clinical studies in 2017.



About Fruquintinib
Fruquintinib is a highly selective small molecule drug candidate that has been shown to inhibit VEGFR 24 hours a day via an oral dose, with lower off-target toxicities compared to other targeted therapies. Its tolerability, along with its clean drug-drug interaction profile demonstrated to date, may enable rational combination with other cancer therapies such as in our ongoing clinical trials of fruquintinib in combination with chemotherapy and targeted therapy.

At an advanced stage, tumors secrete large amounts of VEGF, a protein ligand, to stimulate formation of excessive vasculature (angiogenesis) around the tumor to provide greater blood flow, oxygen, and nutrients to the tumor. VEGF and VEGFR play pivotal roles in tumor-related angiogenesis, and fruquintinib inhibits the VEGF/VEGFR pathway. This represents an important therapeutic strategy in blocking the development of new blood vessels essential for tumors to grow and invade.

Fruquintinib is currently under joint development in China by Chi-Med and its partner Eli Lilly and Company ("Lilly"). Chi-Med and Lilly jointly announced top-line results from the FRESCO CRC trial on March 3, 2017. In addition, fruquintinib is being studied in China in a Phase III pivotal trial in non-small cell lung cancer ("NSCLC"), known as FALUCA; and a Phase II study using fruquintinib combined with Iressa (gefitinib) in the first-line setting for patients with advanced or metastatic NSCLC. Other studies currently being planned, and soon to be initiated, include a Phase III study in gastric cancer in combination with paclitaxel in China, new studies in the United States, and certain exploratory studies in combination with other oncology agents.

About Chi-Med
Chi-Med is an innovative biopharmaceutical company which researches, develops, manufactures and sells pharmaceuticals and healthcare products. Its Innovation Platform, Hutchison MediPharma Limited, focuses on discovering and developing innovative therapeutics in oncology and autoimmune diseases for the global market. Its Commercial Platform manufactures, markets, and distributes prescription drugs and consumer health products in China.

Chi-Med is majority owned by the multinational conglomerate CK Hutchison Holdings Limited (SEHK: 0001). For more information, please visit: www.chi-med.com.

On June 5, 2017 Sierra Oncology, Inc. (NASDAQ: SRRA), a clinical stage drug development company focused on advancing next generation DNA Damage Response (DDR) therapeutics for the treatment of patients with cancer, reported on the initial progress of the two ongoing Phase 1 trials of its Chk1 inhibitor, SRA737. In addition, today Sierra is presenting two posters describing the innovative clinical designs of these trials at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held in Chicago (Press release, Sierra Oncology, JUN 5, 2017, View Source [SID1234519421]).

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"The Dose Escalation Phase of our monotherapy study for SRA737 employs an accelerated titration design which has allowed us to rapidly and efficiently advance through several 100% dose escalations with single patient cohorts," said Dr. Barbara Klencke, Chief Development Officer of Sierra Oncology. "We have not yet observed any dose limiting toxicity and are achieving excellent exposure with several cohorts having surpassed the proposed minimum efficacious plasma concentration for SRA737 based on preclinical modelling. This has enabled the commencement of the parallel Cohort Expansion Phase of the study, described in detail in one of our posters presented at ASCO (Free ASCO Whitepaper) today. This innovative clinical trial design will enroll prospectively-selected genetically-defined patients into five indication-specific cohort expansions at potentially active dose levels."

The SRA737 Phase 1 monotherapy trial has advanced through six single patient dose cohorts of 20, 40, 80, 160, 300 and 600 mg/day, administered under a continuous daily oral dosing regimen in 28-day cycles. Dose escalation will continue until a maximum tolerated dose (MTD) is reached, in parallel with ongoing Cohort Expansion enrollment.
Preliminary observations from the ongoing monotherapy study are as follows:
SRA737 has been well-tolerated to date: No Grade 2 or higher SRA737-related Adverse Events have been reported.
No dose-limiting toxicities have been observed and an MTD has not been reached.

Dose-proportional exposure: Pharmacokinetic (PK) parameters for SRA737 have been generally linear across the dose range tested to date.

Plasma concentrations of SRA737 exceeding the proposed minimum efficacious threshold (Cmin) of 100 nM were maintained for 24 hours post-dose at the 160 mg/day dose level and above.

Having successfully surpassed the proposed minimum efficacious exposure threshold, the Cohort Expansion Phase of the trial has commenced and is enrolling patients with tumors identified to have genetic aberrations hypothesized to confer sensitivity to Chk1 inhibition via synthetic lethality into five indication-specific cohorts: colorectal, head and neck, non-small cell lung, ovarian, and prostate cancers.

For the Phase 1 Chemotherapy Combination study, Stage 1, which is evaluating SRA737 in combination with gemcitabine and cisplatin, has concluded enrolment and the study has transitioned to Stage 2. This stage is seeking to establish the safety profile, determine the MTD and to propose a recommended dose for further development of SRA737 in combination with low-dose gemcitabine. Once an MTD and dosing schedule have been determined, the study will also evaluate the preliminary efficacy of SRA737 in combination with low-dose gemcitabine in indication-specific cohorts of prospectively-selected, genetically-defined subjects with bladder or pancreatic cancer.

"In addition to advancing our novel synthetic lethality-oriented monotherapy study, we are also excited by the potential for SRA737 to combine synergistically with other agents. Gemcitabine is a potent inducer of replication stress and DNA damage via multiple mechanisms, and represents a rational drug combination for SRA737, given Chk1’s fundamental biological role in responding to such stressors. Our preclinical modeling demonstrates robust synergistic anti-tumor activity of SRA737 in combination with low-dose gemcitabine," added Dr. Nick Glover, President and CEO of Sierra Oncology. "We expect to accrue a solid understanding of dose, schedule, pharmacodynamic and pharmacokinetic parameters for SRA737 from these two studies, and the data observed to date are encouraging and consistent with our preclinical research. Our SRA737 development program remains on track and we expect to provide an update from these studies, including potential preliminary activity data, in early 2018."

About SRA737
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of important cell cycle checkpoints and a central mediator of the DDR network. In cancer cells, replication stress induced by oncogenes (e.g., MYC or RAS) or genetic mutations in DNA repair machinery (e.g., BRCA1 or FA) combined with loss of function in tumor suppressors (e.g., TP53 or ATM) results in persistent DNA damage and genomic instability leading to an increased dependency on Chk1 for survival. Targeted inhibition by SRA737 may therefore be synthetically lethal to these cancer cells and have utility as a monotherapy in a range of tumor indications.

Profound mechanistic potentiation has also been reported when Chk1 inhibition is combined with DNA damaging cytotoxic agents or radiation. The widely-used chemotherapy gemcitabine is a strong exogenous inducer of replication stress and preclinical modeling demonstrates robust synergistic anti-tumor activity for SRA737 potentiated by gemcitabine.

SRA737 was discovered and initially developed at the Cancer Research UK (CRUK) Cancer Therapeutics Unit at the Institute of Cancer Research (ICR).

About the SRA737 Monotherapy Trial Design
This first-in-human, multicenter, Phase 1 Monotherapy study consists of two phases, a Dose Escalation Phase and a Cohort Expansion Phase, being run concurrently.

The Dose Escalation Phase of the SRA737 Phase 1 monotherapy trial is investigating the safety and tolerability of SRA737 and seeking to identify its optimal dose, schedule, and maximum tolerated dose (MTD). Single patient cohorts will receive escalating doses of SRA737, starting at 20 mg, administered orally on a continuous daily dosing schedule in 28-day cycles until SRA737-related Grade 2 toxicity is observed in a dose escalation subject during Cycle 1. At that point, that dose level and all subsequent dose level cohorts will be expanded to three to six subjects, following a rolling six design. Intensive PK and pharmacodynamic assessments will be obtained on all subjects.
In the Cohort Expansion Phase, enrollment into five indication-specific cohort expansions was initiated once the minimum efficacious dose level was reached. Subjects with colorectal, head and neck, non-small cell lung, ovarian, and prostate cancer will be selected based on prospective, tumor tissue genetic profiling using Next Generation Screening (NGS) and must have tumors that harbor a minimum of two genomic alterations hypothesized to confer sensitivity to Chk1 inhibition. The Dose Escalation Phase will continue concurrently until the MTD and Recommended Phase 2 Dose are identified.

About the SRA737 Chemotherapy Combination Trial Design
This first-in-human Phase 1, multicenter study consists of two stages:
In Stage 1, a triplet combination (SRA737 with gemcitabine and cisplatin) is being evaluated in subjects with solid tumors. Cohorts consisting of three to six subjects will receive escalating doses of SRA737. Intensive PK and pharmacodynamic assessments will be obtained on all subjects. Enrolment for this stage has concluded and the study has transitioned to Stage 2.

In the Dose Escalation Phase of Stage 2, cohorts of three to six subjects will be given escalating doses of SRA737 on an intermittent schedule in addition to low-dose gemcitabine until the combination MTD is reached. The starting dose of SRA737 for the first cohort was 40 mg. SRA737 will be administered orally on days 2, 3, 9, 10, 16 & 17 of a 28-day cycle; 300 mg/m2 of gemcitabine will be administered intravenously on days 1, 8, & 15.

Once the MTD of SRA737 in combination with gemcitabine has been identified, the Cohort Expansion Phase of Stage 2 will begin. Qualifying patients will be enrolled into two indication-specific cohort expansions, bladder cancer and pancreatic cancer. To qualify for enrolment into these cohorts, the subject’s tumor must have a confirmed minimum of two genomic alterations hypothesized to confer sensitivity to Chk1 inhibition, determined using NGS.
About the SRA737 ASCO (Free ASCO Whitepaper) 2017 Poster Presentations

Two "Trials in Progress" posters describing the innovative Phase 1 clinical designs for SRA737 are being presented today at the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting. The posters are available on the company’s website at www.sierraoncology.com

SRA737 Monotherapy Poster
Title: A phase I study of SRA737 (formerly known as CCT245737) administered orally in patients with advanced cancer.
Trials in Progress Abstract: #TPS2607
Poster: #93b
Poster Session: Developmental Therapeutics – Clinical Pharmacology and Experimental Therapeutics
Date and Time: Monday, June 5, 2017, 8:00 – 11:30am CT
Location: McCormick Place, Event room: Hall A, 2301 S King Dr., Chicago, Illinois

SRA737 Chemotherapy Combination Poster
Title: A phase I study of oral SRA737 (formerly CCT245737) given in combination with gemcitabine plus cisplatin or gemcitabine alone in patients with advanced cancer.
Trials in Progress Abstract: #TPS2613
Poster: #96b
Poster Session: Developmental Therapeutics – Clinical Pharmacology and Experimental Therapeutics
Date and Time: Monday, June 5, 2017, 8:00 – 11:30am CT
Location: McCormick Place, Event room: Hall A, 2301 S King Dr., Chicago, Illinois

On June 3, 2017 TG Therapeutics (NASDAQ: TGTX) reported positive results from its Phase 3 GENUINE trial of TG-1101 (ublituximab) plus ibrutinib in patients with previously treated high risk Chronic Lymphocytic Leukemia (CLL) (Press release, TG Therapeutics, JUN 5, 2017, View Source [SID1234519420]). Data from this trial was presented today by Dr. Jeff Sharman, Medical Director, Hematology Research, US Oncology in an oral session during the 53rd American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL.

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Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, "Patients with high-risk CLL have the poorest outcomes on ibrutinib and are in need of a more efficacious treatment. We believe the data presented today demonstrate that the addition of TG-1101 to ibrutinib improves patient outcomes across multiple measures." Mr. Weiss continued, "In addition to increasing the overall number of patients that responded to treatment with ibrutinib, adding TG-1101 to ibrutinib increased the number of patients with bone marrow confirmed CR’s, MRD negativity in peripheral blood, deepened nodal responses, and resulted in fewer patients progressing on therapy. Collectively, we see the consistent pattern of enhanced benefit as providing a compelling case for combining TG-1101 with ibrutinib in these hard to treat patients with high-risk CLL. We look forward to sharing these data with the FDA later this year to discuss filing for accelerated approval. We would like to thank our investigators and their patients for their participation in this important clinical trial."

Highlight’s from this presentation include the following:

Oral Presentation: Ublituximab and ibrutinib for previously treated genetically high-risk chronic lymphocytic leukemia: Results of the GENUINE Phase 3 study

This presentation includes data from the GENUINE Phase 3 trial, a multicenter, randomized trial (NCT02301156), which assessed the efficacy and safety of TG-1101 plus ibrutinib versus ibrutinib alone in patients with high risk CLL. For the trial, high-risk was defined as having any one or more of the following centrally confirmed features: 17p deletion, 11q deletion or p53 mutation. The GENUINE study was designed to demonstrate the value of adding TG-1101, a potent next generation glycoengineered anti-CD20 monoclonal antibody to ibrutinib monotherapy in high-risk CLL, and was powered to show a statistically significant improvement in ORR of 30%, with a minimal absolute detectable difference between the two arms of approximately 20%.

The trial met its primary endpoint, demonstrating a statistically significant improvement in Overall Response Rate (ORR), as assessed by blinded independent central radiology and hematology review by iwCLL (Hallek 2008) criteria, compared to ibrutinib alone in both the Intent to Treat (ITT) population (p=0.001) and Treated population (p<0.001). Per iwCLL guidelines, all responders required confirmation of response for a minimum duration of 2 months. The ITT population includes all 126 randomized patients (64 in the TG-1101 plus ibrutinib arm and 62 in the ibrutinib alone arm) while the Treated population includes all ITT patients that received at least one dose of either study drug (59 in the TG-1101 plus ibrutinib arm and 58 in the ibrutinib alone arm).




Patient Demographics

One hundred and twenty-six (126) patients were randomized on the GENUINE Phase 3 trial. 100% of patients were high-risk and had either 17p deletion, 11q deletion, or p53 mutation. Sixty-four percent (64%) of patients in the TG-1101 plus ibrutinib arm and 66% of patients in the Ibrutinib alone arm had 17p deletion and/or a p53 mutation while 36% and 34% of patients in the TG-1101 plus ibrutinib and ibrutinib alone arms, respectively, had an 11q deletion only. The median age of patients on either arm was 67 years and the median number of prior lines of therapy for either arm was 3.

Safety & Tolerability

One hundred and seventeen (117) patients were evaluable for safety (59 patients in the TG-1101 plus ibrutinib arm, and 58 patients in the ibrutinib alone arm). The combination was well tolerated and, apart from infusion related reactions, the addition of TG-1101 did not appear to alter the safety profile of ibrutinib monotherapy. Neutropenia, occurring in 9% of patients, was the most commonly reported Grade 3/4 Adverse Event (AE) in the combination arm, followed by infusion related reactions and anemia, each reported in 5% of patients. Notably, the majority of infusion related reactions (IRR) were Grade 1 or 2 in severity, with only 5% Grade 3/4 IRR observed. Median follow-up for this study was approximately 11.4 months.

Clinical Activity

Response Rates


TG-1101 plus Ibrutinib
Ibrutinib
P-value
Treated Population (n)
n=59
n=58

Overall Response Rate (ORR)
78%
45%
P<0.001
Complete Response (CR)
7%
0%
NS
MRD-Negative
19%
(n=53) *
2%
(n=53) *
P<0.01
*Patients evaluable for MRD included those enrolled >4 months prior to data cutoff date of February 15, 2017. MRD analyzed by central lab, 7-color flow cytometry


In addition to the improvements in ORR, CR and MRD-negativity, a trend in improvement of Progression Free Survival (PFS) was observed in the combination arm of TG-1101 plus ibrutinib as compared to ibrutinib alone (Hazard Ratio = 0.559; p=NS).

ABOUT THE PHASE 3 GENUINE STUDY

The Phase 3 GENUINE study is a randomized, open label, multicenter clinical trial to evaluate the safety and efficacy of TG-1101 (ublituximab) plus ibrutinib compared to ibrutinib alone in adult patients with high-risk Chronic Lymphocytic Leukemia (CLL) who received at least one prior therapy for their disease.

The study was conducted at 160 clinical trial sites in the US and Israel and randomized 126 patients. Patients received ibrutinib orally at 420 mg once daily in both arms and in the combination arm those patients also received intravenous infusions of TG-1101 at 900 mg dosed on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6. Patients in the combination arm who had not progressed received quarterly infusions of TG-1101 maintenance at 900 mg.

PRESENTATION DETAILS:

The above referenced presentation isnow available on the Publications page, located within the Pipeline section, of the Company’s website at www.tgtherapeutics.com/publications.cfm.

On June 5, 2017 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported smart chemotherapy DS-8201 demonstrated a favorable safety profile and promising antitumor activity in patients with HER2-expressing tumors, including pre-treated metastatic breast and gastric cancer (Press release, Daiichi Sankyo, JUN 5, 2017, View Source [SID1234519417]). These data were highlighted as part of a Clinical Science Symposium at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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Preliminary results from the dose expansion part of the phase 1 study of DS-8201 in a subgroup analysis of HER2-expressing metastatic breast cancer patients pre-treated with ado-trastuzumab emtansine (T-DM1) and pertuzumab demonstrated a 46.7 percent overall response rate (14 of 30 patients) and a 100 percent disease control rate (30 of 30 patients) to date. An overall response rate of 45.7 percent (16 of 35 patients) and disease control rate of 100 percent (35 of 35 patients) was observed in patients pre-treated with only T-DM1.

Antibody drug conjugates (ADCs) are a type of targeted cancer medicine that deliver cytotoxic chemotherapy ("payload") directly to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Using Daiichi Sankyo’s proprietary ADC technology, DS-8201 is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor (DXd) payload by a tetrapeptide linker designed to deliver enhanced cancer cell destruction upon release inside the cell and reduce systemic exposure to the cytotoxic payload (or chemotherapy).

"The significant tumor shrinkage and sustained tumor control that was demonstrated by DS-8201 is impressive and further confirms the initial antitumor activity shown in the dose escalation part of this study," said Toshihiko Doi, MD, PhD, Department of Experimental Therapeutics, National Cancer Center Hospital East, and study investigator. "These data suggest that DS-8201 may be a promising potential treatment for patients with HER2-expressing metastatic breast cancer whose tumors are no longer controlled with available treatment options like T-DM1 and pertuzumab."

Thirty-nine of 50 patients with HER2-expressing metastatic breast cancer are continuing to receive treatment. To date, median progression free survival has reached 45.4 weeks (95 percent CI: 32.1, NA). Eleven patients have discontinued treatment due to adverse events (3 patients), progressive disease (6 patients) and other reasons (2 patients).

"These results demonstrate that the smart delivery of chemotherapy by DS-8201 to cancer cells may be effective and safe in treating tumors that express HER2," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "Based on these results, we are accelerating the development of DS-8201 and our ADC technology seeking to bring a unique precision medicine to patients and physicians who have exhausted current treatment options."

About the DS-8201 Phase 1 Study
DS-8201 is currently being evaluated in an open-label two-part phase 1 dosing study in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of the study was to assess the safety and tolerability of DS-8201 and determine the maximum tolerated dose (MTD). No dose limiting toxicity was seen administering DS-8201 up to 8.0 mg/kg every three weeks and the maximum tolerated dose was not reached.

In the dose expansion part of the study, DS-8201 is given in one of two doses (5.4 mg/kg and 6.4 mg/kg) to patients in one of four cohorts: patients with ado-trastuzumab emtansine (T-DM1)-treated HER2-positive breast cancer; patients with trastuzumab-treated HER2-positive gastric cancer or gastroesophageal junction adenocarcinoma; patients with HER2 low-expressing breast cancer; and patients with other HER2-expressing solid malignant tumors. Patient enrollment in the two breast cancer cohorts is ongoing in the U.S. and Japan. For more information about the study, please visit ClinicalTrials.gov.

A total of 134patients have been treated to date in both the dose escalation (24 patients) and dose expansion (110 patients) parts of the study. The most common any-grade adverse events observed in the study to date included nausea (66.9 percent), decreased appetite (57.9 percent), vomiting (36.8 percent) and decreased platelet count (34.6 percent). Grade 4 adverse events included decreased platelet count (3.8 percent), decreased neutrophil count (3.0 percent), anemia (1.5 percent), and decreased white blood cell count (1.5 percent).

Preliminary results in the overall population of HER-expressing solid tumors demonstrated an overall response rate of 40.2 percent (39 of 97 patients) with a disease control rate of 91.8 percent. In the cohort enrolling patients with trastuzumab-treated HER2-positive gastric or gastroesophageal junction adenocarcinoma, a preliminary overall response rate of 44.4 percent (16 of 36 patients) and a disease control rate of 88.9 percent (32 of 36 patients) was shown to date with DS-8201. In a sub-group of patients pre-treated with CPT-11 (irinotecan), an overall response rate of 44.4 percent (8 of 18 patients) and disease control rate of 94.4 percent (17 of 18 patients) was demonstrated to date. A total of 22 out of 39 patients are still receiving treatment with median progression free survival of 27.3 weeks (95 percent CI: 13.4, NA). Seventeen patients have discontinued treatment due to adverse events (6 patients) and progressive disease (11 patients).

About DS-8201
DS-8201 is the lead product in the Antibody Drug Conjugate (ADC) Franchise of the Daiichi Sankyo Cancer Enterprise. DS-8201 is currently in phase 1 clinical development for HER2-positive advanced or metastatic breast cancer and 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). DS-8201 has not been approved for any indication in any country.

On June 5, 2017 CEL-SCI Corporation (NYSE MKT: CVM) reported that it has responded to the U.S. Food and Drug Administration’s (FDA) most recent communication from May 2017 about the clinical hold imposed on the Company’s Phase 3 head and neck cancer study with Multikine* (Leukocyte Interleukin, Inj.) (Press release, Cel-Sci, JUN 5, 2017, View Source [SID1234519416]).

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The hold issues addressed in the FDA communication were that the study’s Investigator Brochure (IB) and the "Dear Investigator" letter need to be revised. Specific deficiencies and their locations in each of the documents were identified, and directions were given as to the specific information that should be included in the revisions of these documents. CEL-SCI revised the documents exactly as directed by the FDA. If the FDA finds the revisions made to the two documents to be satisfactory, CEL-SCI is hopeful that all of the clinical hold issues have now been addressed, and the FDA will consider lifting the clinical hold.

As of September 2016, nine hundred twenty-eight (928) head and neck cancer patients have been enrolled and have completed treatment in the Phase 3 study. In accordance with the study protocol, the FDA’s instructions, and subject to the clinical hold, CEL-SCI continues to follow these patients.

The study endpoint is a 10% increase in overall survival of patients between the two main comparator groups in favor of the group receiving the Multikine treatment regimen. The determination if the study end point is met will occur when there are a total of 298 deaths in those two groups.