On October 20, 2019 Innovent Biologics, Inc. ("Innovent" or "the Company") (HKEX: 01801), a world-class biopharmaceutical company that develops and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic and other major diseases, reported positive updated results from the Incyte-sponsored Phase 2 trial of pemigatinib in patients with previously treated, advanced cholangiocarcinoma which were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 (Press release, Innovent Biologics, OCT 20, 2019, View Source [SID1234542371]).

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In December 2018, Innovent and Incyte entered into a strategic collaboration for three clinical-stage product candidates discovered and developed by Incyte, including pemigatinib (FGFR1/2/3 inhibitor), itacitinib (JAK1 inhibitor) and parsaclisib (PI3Kδ inhibitor). Under the terms of the agreement, Innovent has received the rights to develop and commercialize the three assets in hematology and oncology in Mainland China, Hong Kong, Macau and Taiwan.

The updated results from the Phase 2 FIGHT-202 trial evaluating pemigatinib, a selective fibroblast growth factor receptor (FGFR) inhibitor, as a treatment for patients with previously treated, locally advanced or metastatic cholangiocarcinoma presented at ESMO (Free ESMO Whitepaper) 2019 include the final result for the primary endpoint. In patients harboring FGFR2 fusions or rearrangements (Cohort A), pemigatinib monotherapy resulted in an overall response rate (ORR) of 36 percent (primary endpoint), and median progression free survival (PFS) of 6.9 months (secondary endpoint) with a median follow-up of 15 months. Pemigatinib was generally well tolerated.

The data support the planned submission of a New Drug Application (NDA) by Incyte to the U.S. Food and Drug Administration (FDA) for pemigatinib before the end of 2019.

Cholangiocarcinoma is a rare cancer that forms in the bile duct. It is classified based on its origin: intrahepatic cholangiocarcinoma (iCCA) occurs in the bile duct inside the liver and extrahepatic cholangiocarcinoma occurs in the bile duct outside the liver. Patients with cholangiocarcinoma are often diagnosed at a late or advanced stage when the prognosis is poor. The incidence of cholangiocarcinoma varies regionally and ranges between 0.3– 3.4 per 100,000 in North America and Europe. FGFR2 fusions or rearrangements occur almost exclusively in iCCA, where they are observed in 10-16 percent of patients.

Key Findings from FIGHT-202

Updated data presented at ESMO (Free ESMO Whitepaper) show that in patients with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements (Cohort A, n=107), pemigatinib monotherapy resulted in a confirmed overall response rate (ORR) of 36 percent based on an independent central radiographic review, including 3 patients with a complete response (CR) and 35 patients with a partial response (PR). In these patients, the disease control rate (DCR) was 82 percent, median duration of response (DOR) was 7.5 months, and median progression free survival (PFS) was 6.9 months. Preliminary overall survival (OS) data were encouraging (median: 21.1 months) and follow-up will continue as these data are not yet mature.

FIGHT-202 Overall Response Rates (ORR). Durability of Response (DOR). Disease Control Rates (DCR) and Progression-Free Survival (PFS) by Patient Cohort

Cohort A

FGFR2 Fusions or Rearrangements

Cohort B

Other FGF/FGFR Genetic Alterations

Cohort C

No FGF/FGFR Genetic Alterations

(N=107)

(N=20)

(N=18)

ORR, % (95% CI)

36 (27-45)

0

0

3 CR (3)

0

0

Best OR, n（%）

35 PR (33)

0

0

50 SD (47)

8 SD (40)

4 SD (22)

Median DOR,

Months (95% CI)

7.5 (5.7-14.5)

–

–

DCR, % (95% CI)

82 (74-89)

40 (19-64)

22 (6-48)

Median PFS,

Months (95% CI)

6.9 (6.2-9.6)

2.1 (1.2-4.9)

1.7 (1.3-1.8)

Median OS,

Months（95% CI）

21.1 (14.8-NE)

6.7 (2.1-10.6)

4.0 (2.3-6.5)

NE: not evaluable

Note: One patient did not have confirmed FGF/FGFR status by central laboratory and was included in the safety analysis but was not assigned to any cohort for efficacy.

The safety analysis, including 146 patients, showed that pemigatinib was generally well tolerated. Grade 1 or 2 hyperphosphatemia, the most common treatment-emergent adverse event (TEAE; 60 percent), was managed with a low phosphate diet, phosphate binders and diuretics, or dose reduction or interruption. The most common Grade ≥3 TEAE was hypophosphatemia (12 percent); none of the cases was considered clinically significant or serious and none led to dose reduction or discontinuation. Serous retinal detachment was observed in 4 percent of patients (Grade ≥3, 1 percent) with none of the cases resulting in clinical sequelae.

About FIGHT-202

The FIGHT-202 Phase 2, open-label, multicenter study (NCT02924376) is evaluating the safety and efficacy of pemigatinib – a selective fibroblast growth factor receptor (FGFR) inhibitor – in adult (age ≥ 18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGF/FGFR status.

Patients were enrolled into one of three cohorts – Cohort A (FGFR2 fusions or rearrangements), Cohort B (other FGF/FGFR genetic alterations) or Cohort C (no FGF/FGFR genetic alterations). All patients received 13.5 mg pemigatinib orally once daily (QD) on a 21-day cycle (two weeks on/one week off) until radiological disease progression or unacceptable toxicity.

The primary endpoint of FIGHT-202 is overall response rate (ORR) in Cohort A, assessed by independent review per RECIST v1.1. Secondary endpoints include ORR in Cohorts B, A plus B, and C; progression free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR) and safety in all cohorts.

For more information about FIGHT-202, visit:

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About FIGHT

The FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program includes ongoing Phase 2 and 3 studies investigating safety and efficacy of pemigatinib therapy across several FGFR-driven malignancies. Phase 2 monotherapy studies include FIGHT-202, as well as FIGHT-201 investigating pemigatinib in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 mutations or fusions/rearrangements; FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 fusions/rearrangements; FIGHT-207 in patients with previously treated, locally-advanced/metastatic or surgically unresectable solid tumor malignancies harboring activating FGFR mutations or fusions/rearrangements, irrespective of tumor type. FIGHT-205 is a Phase 2 study investigating pemigatinib plus pembrolizumab combination therapy and pemigatinib monotherapy in patients with previously untreated, metastatic or unresectable bladder cancer harboring FGFR3 mutations or fusions/rearrangements who are not eligible to receive cisplatin. FIGHT-302 is a recently initiated Phase 3 study investigating pemigatinib as a first-line treatment for patients with cholangiocarcinoma with FGFR2 fusions or rearrangements.

About FGFR and Pemigatinib

Fibroblast growth factor receptors (FGFRs) play an important role in tumor cell proliferation and survival, migration and angiogenesis (the formation of new blood vessels). Activating fusions, rearrangements, translocations and gene amplifications in FGFRs are closely correlated with the development of various cancers.

Pemigatinib is a potent, selective, oral inhibitor of FGFR isoforms 1, 2 and 3 which, in preclinical studies, has demonstrated selective pharmacologic activity against cancer cells with FGFR alterations discovered and developed by Incyte. The U.S. Food and Drug Administration (FDA) has granted pemigatinib Breakthrough Therapy designation for the treatment of previously treated, advanced/metastatic or unresectable FGFR2 translocated cholangiocarcinoma. The FDA’s Breakthrough Therapy designation is designed to expedite the development and review of drugs for serious conditions that have shown encouraging early clinical results and may demonstrate substantial improvements over available medicines.

On October 18, 2019 SFA Therapeutics, Inc. reported that their CEO, Dr. Ira Spector, will update the company’s clinical development plans for several new therapeutic agents they have derived from the human microbiome (Press release, SFA Therapeutics, OCT 18, 2019, View Source [SID1234542363]). The presentation will be delivered as part of the prestigious Bio Investors Forum on October 23rd at 9:45AM in the Elizabethan Room of the Westin St. Francis Hotel in San Francisco, CA.

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On October 18, 2019 Isofol Medical AB (publ), (Nasdaq First North Premier: ISOFOL), reported the successful completion of Japan’s Pharmaceutical and Medical Devices Agency (PMDA) review of the Clinical Trial Notification (CTN), allowing the start of the pivotal Phase 3 AGENT clinical study in metastatic colorectal cancer (mCRC) at Japanese sites (Press release, Isofol Medical, OCT 18, 2019, View Source [SID1234542364]). Based on feedback from the PMDA, Isofol expects that the data from the ongoing Phase 3 AGENT clinical study, if positive, will serve as the basis to submit the application for manufacturing and marketing approval in Japan.

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A CTN is equivalent to a U.S. Investigational New Drug application (IND). In combination with the existing IND for arfolitixorin in the U.S. and investigational medicinal product (IMP) designation in Europe, the recently received CTN in Japan creates potential for global approval of arfolitixorin pending positive results from the ongoing Phase 3 clinical trial.

"Japan represents a very important potential market for Isofol and one we see as a top priority as we advance the development of arfolitixorin in mCRC patients globally. There is a significant unmet need for new treatment options for mCRC in Japan, particularly in the first line setting," said Anders Rabbe, chief executive officer of Isofol. "We look forward to launching the pivotal Phase 3 AGENT clinical study in Japan in early 2020, and continuing our discussions with the PMDA and potential partners in Japan as we map out a path to market for our drug candidate."

Roger Tell, M.D., Ph.D., chief medical officer of Isofol, added, "We are excited about this important milestone and the degree of enthusiasm expressed by Japanese key opinion leaders as well as clinical investigators who will participate in the study. With the CTN now in effect, the next steps include obtaining Institutional Review Board approval and finalizing agreements with each of the participating clinical sites. In the near term, Isofol will be focusing on these activities, with support from our Japanese CRO, CMIC Shift Zero, in preparation for the start of enrolment."

AGENT (ISO-CC-007) is expected to enrol 440 mCRC patients in North America and Europe, all treated in the first line setting, who will receive either arfolitixorin or leucovorin, both in combination with 5-FU, oxaliplatin and bevacizumab. The primary endpoint is overall response rate (ORR) and the key secondary endpoints are progression free survival (PFS) and duration of response (DOR). Top-line data from the study are expected in 2021. The recruitment of patients is ongoing in North America and Western Europe and will now be expanded to include patients from Japan as well.

About the AGENT study

The Phase 3 AGENT clinical study is a randomized, controlled, multi-centre study assessing the efficacy and safety of arfolitixorin, [6R]-5,10-methylene-tetrahydrofolic acid (MTHF), compared to leucovorin, both used in combination with 5-FU, oxaliplatin, and bevacizumab, in first line metastatic colorectal cancer patients. Patients are randomized in a 1:1 ratio and the primary endpoint is overall response rate (ORR). The key secondary endpoints are progression free survival (PFS) and duration of response (DOR). Other secondary endpoints include overall survival (OS), number of curative metastasis resections, safety, and patient reported outcomes such as quality of life (QoL). Exploratory endpoints include pharmacokinetic (PK) measurements and level of gene expression of folate relevant genes in tumour cells. The study is designed to show superiority for arfolitixorin over leucovorin. The study is ongoing at approximately 70 sites in the U.S., Canada and Western Europe and will now be expanded to include Japanese hospitals as well. Further information about the study, including eligibility requirements, is available at www.clinicaltrials.gov Clinical trials.gov id:NCT03750786.

About arfolitixorin

Arfolitixorin is Isofol’s proprietary drug candidate being developed to increase the efficacy of standard of care chemotherapy for advanced colorectal cancer. The drug candidate is currently being studied in a global Phase 3 clinical trial, AGENT. As the key active metabolite of the widely used folate-based drugs, arfolitixorin can potentially benefit all patients with advanced colorectal cancer, as it does not require complicated metabolic activation to become effective.

On October 18, 2019 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported the presentation of data supporting the ability of the DecisionDx-Melanoma gene expression profile (GEP) test to identify T1 (tumor depth of 1 mm or less) melanoma patients at low risk for a positive sentinel lymph node (SLN) at the American Society of Dermatopathology (ASDP) 56th Annual Meeting in San Diego from October 17-20 (Press release, Castle Biosciences, OCT 18, 2019, View Source [SID1234542365]).

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The study titled, "Identification of T1 melanoma patients at low risk for a positive sentinel lymph node (SLN) using a 31-gene expression profile (31-GEP)" (Abstract #262), will be presented as a poster at the meeting.

Study Background:

Current guidelines recommend that clinicians discuss the sentinel lymph node biopsy (SLNB) procedure with patients who have greater than 5% likelihood of SLN positivity; the guidelines do not recommend the procedure for patients with less than 5% likelihood of SLN positivity. Patients with T1 melanoma tumors have a 5.4% risk of SLN positivity overall.
The DecisionDx-Melanoma test is a prognostic test for cutaneous melanoma that predicts 5-year risk of metastasis as low risk (Class 1, 1A lowest risk) or high risk (Class 2, 2B highest risk).
The DecisionDx-Melanoma test has been previously validated to guide SLNB decisions, as patients with T1-T2 melanoma (tumor depth of 2 mm or less) with a Class 1A result had very low rates of SLN positivity.
This study was designed to evaluate the ability of the DecisionDx-Melanoma test to identify T1 melanoma patients with low risk for a positive SLN, using the combination of the previously published cohort with a novel cohort, totaling 910 consecutively tested T1 melanoma patients collected prospectively or retrospectively under IRB-approved protocols.
Key Findings:

For patients with T1 tumors of any age and a Class 1A test result, SLN positivity was 3.5%, significantly less than patients with a Class 1B-2B result (p=0.0005), and below the 5% threshold at which guidelines do not recommend the procedure.
For patients with T1 tumors 55 years of age or older and a Class 1A test result, SLN positivity was 2.3%, significantly less than patients with a Class 1B-2B result (p=0.002), and below the 5% threshold at which guidelines do not recommend the procedure.
Use of the DecisionDx-Melanoma test to guide SLNB decisions in patients with T1 melanoma could reduce SLNB surgical procedures by 80% in patients 55 years of age or older, as 272 of 339 patients who underwent this procedure had a Class 1A result.
Class 1A patients with T1 melanoma had recurrence free survival of 96.9% and distant metastasis-free survival of 97.3% on a retrospective dataset of 345 T1 patients with long-term follow-up, supporting that this population can safely avoid the SLNB surgical procedure.
"The study results show that use of the DecisionDx-Melanoma test can identify T1 patients who are at low risk for a positive sentinel lymph node and can guide sentinel lymph node biopsy discussions," said Federico A. Monzon, M.D., FCAP, chief medical officer at Castle Biosciences. "Furthermore, the identification of patients who are unlikely to benefit from sentinel lymph node biopsy can reduce unnecessary surgical procedures and have a positive impact on the allocation of healthcare resources."

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 3,900 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and five prospective risk of recurrence studies including more than 780 patients. Prediction of the likelihood of sentinel lymph node positivity has also been validated in three prospective multicenter study cohorts that included more than 2,000 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

On October 18, 2019 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a negative opinion on the Marketing Authorization Application (MAA) for quizartinib for the treatment of adults with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML) (Press release, Daiichi Sankyo, OCT 18, 2019, View Source [SID1234542366]).

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The CHMP opinion is based on the MAA submission of data from the global pivotal QuANTUM-R study of quizartinib. Results from QuANTUM-R were published in The Lancet Oncology.[1]

"While we are disappointed by this opinion, we will evaluate feedback received from the CHMP in order to determine next steps for quizartinib for the treatment of patients with relapsed/refractory FLT3-ITD AML in Europe," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "Despite this setback, we continue to believe in the potential benefit of quizartinib for patients with FLT3-ITD AML and we look forward to the results of the global, pivotal phase 3 QuANTUM-First study evaluating quizartinib in combination with chemotherapy for patients with newly-diagnosed FLT3-ITD AML. We remain committed to bringing quizartinib forward as a potential treatment option for this aggressive and difficult-to-treat subtype of AML in the U.S., Europe and other parts of the world."

About Quizartinib
Quizartinib, an oral FLT3 inhibitor, is the lead product in the AML Franchise of Daiichi Sankyo.
Quizartinib currently is approved for use in Japan under the brand name VANFLYTA for the treatment of adult patients with relapsed/refractory FLT3-ITD AML, as detected by an approved test. It was launched in Japan on October 10, 2019.

Enrollment into QuANTUM-First, a global, pivotal phase 3 study evaluating quizartinib in combination with standard chemotherapy in newly diagnosed FLT3-ITD AML, was recently completed.

Other ongoing studies include phase 1/2 development for pediatric and young adult relapsed/refractory FLT3-ITD AML in North America and Europe; and phase 1 development in combination with milademetan, an investigational MDM2 inhibitor, for relapsed/refractory FLT3-ITD AML and newly-diagnosed FLT3-ITD AML unfit for intensive chemotherapy in the U.S. Milademetan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About FLT3-ITD AML
AML is an aggressive blood and bone marrow cancer that causes uncontrolled growth and accumulation of malignant white blood cells that fail to function normally and interfere with the production of normal blood cells.[2] In the EU, there are approximately 18,000 new cases of AML each year,[3] and their five-year survival rate is less than 30 percent.[4]

FLT3 gene mutations are one of the most common genetic abnormalities in AML.[5] FLT3-ITD is the most common FLT3 mutation, affecting approximately one in four patients with AML.[6] FLT3-ITD is a driver mutation that presents with high leukemic burden, a poor prognosis and a significant impact on disease management for patients with AML.[7] Patients with FLT3-ITD AML have a worse overall prognosis, including an increased incidence of relapse, an increased risk of death following relapse and a higher likelihood of relapse following hematopoietic stem cell transplantation, as compared to those without this mutation.[8],[9]

About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by three pillars, including our investigational Antibody Drug Conjugate Franchise, Acute Myeloid Leukemia Franchise and Breakthrough Science, we aim to deliver seven distinct new molecular entities over eight years during 2018 to 2025. Our powerful research engines include two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.