On October 21, 2018 Incyte Corporation (Nasdaq:INCY) reported updated data from its ongoing Phase 2 FIGHT-202 trial evaluating pemigatinib (INCB54828), its selective fibroblast growth factor receptor (FGFR) inhibitor, in patients with advanced/metastatic or surgically unresectable cholangiocarcinoma (bile duct cancer) who failed at least one previous treatment (Press release, Incyte, OCT 21, 2018, View Source [SID1234530092]). In patients with FGFR2 translocations who were followed for at least eight months, interim study results demonstrated an overall response rate (ORR) of 40 percent, the primary endpoint, and a median progression free survival (PFS) of 9.2 months, a key secondary endpoint.

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These results are being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in Munich, Germany in a poster presentation on Sunday, October 21 from 12:45 p.m. CEST to 1:45 p.m. CEST (6:45 a.m. ET to 7:45 a.m. ET). (Location: Hall A3 – Poster Area Networking Hub; Abstract #756P)

"We are pleased to share updated interim results from our ongoing FIGHT-202 trial at ESMO (Free ESMO Whitepaper), which underscore the potential of pemigatinib as an effective new treatment option for patients with advanced cholangiocarcinoma who have FGFR2 translocations," said Steven Stein, M.D., Chief Medical Officer, Incyte. "If the full data set warrant it, we look forward to submitting our new drug application to the FDA in 2019, seeking approval of pemigatinib as a first-in-class selective FGFR inhibitor to treat patients with advanced cholangiocarcinoma, a devastating disease."

Cholangiocarcinoma is a cancer that arises from the cells within the bile ducts. It is often diagnosed late (stages III and IV) and the prognosis is poor. It is most common in those over 70 years old and is more common in men than women. FGFR2 fusion genes are drivers of the disease – occurring almost exclusively in patients with intrahepatic cholangiocarcinoma (iCCA), a subset of the disease – and are found in up to 20 percent of iCCA patients. The incidence of cholangiocarcinoma with FGFR2 translocation is increasing and is currently estimated at 2,500-3,000 patients in the U.S., Europe and Japan.

Key Findings from FIGHT-202

Updated, longer-term follow-up data from the interim analysis presented today at ESMO (Free ESMO Whitepaper) (data cut as of July 24, 2018) show that in patients with advanced/metastatic or surgically unresectable iCCA with FGFR2 translocations treated with pemigatinib who had at least eight months of follow up (Cohort A, n=47), the combined overall response rate (ORR) was 40 percent, including 19 (40 percent) patients with confirmed partial responses and 21 (45 percent) patients with stable disease (SD). The combined disease control rate (DCR) was 85 percent (40/47). Additionally, median progression free survival (PFS) was 9.2 months and median overall survival (OS) was 15.8 months.

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

Cohort A

FGFR2 Translocations

(N=47)

Cohort B

Other FGF/FGFR
Genetic Alterations

(N=22)

Cohort C

No FGF/FGFR Genetic
Alterations

(N=18)

ORR, % (95% CI) 40 (26.4-55.7) 0 (0.0-15.4) 0 (0.0-18.5)
Best OR, n (%) 0 CR (0.0)
19 PR (40)

21 SD (45)

0 CR (0.0)
0 PR (0.0)

10 SD (46)

0 CR (0.0)

0 PR (0.0)

4 SD (22)

Median DOR,
Months (95% CI)

NE (6.93-NE)

Median (range) duration
of response has not been
reached

NE (NE-NE)

Median (range) duration
of response has not been
reached

NE (NE-NE)

Median (range) duration
of response has not been
reached

DCR, % (95% CI) 85 (71.7-93.8) 46 (24.4-67.8) 22 (6.4-47.6)
Median PFS,
Months (95% CI)

9.2 (6.44-NE) 2.1 (1.18-6.80) 1.68 (1.38-1.84)
Median OS,
Months (95% CI)

15.8 6.8 4.0
NE = not evaluable, upper limit was not reached

Pemigatinib was well-tolerated. The most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (61 percent), alopecia (42 percent), diarrhea (39 percent), decreased appetite (37 percent) and fatigue (36 percent). Grade ≥3 TEAEs (observed >5 percent of patients) were hypophosphatemia (14 percent), hyponatremia (8 percent), abdominal pain (7 percent) and arthralgia (7 percent). Five patients had TEAEs with a fatal outcome, none of which were related to study treatment.

"I am extremely encouraged by the interim results of the FIGHT-202 study, which demonstrated meaningful clinical activity and promising preliminary progression-free survival estimates, and, as a practicing clinician, I am excited about the potential of pemigatinib to provide a new treatment option for my patients suffering from the life-threatening nature of advanced cholangiocarcinoma," said Antoine Hollebecque, M.D., Institut de Cancérologie Gustave Roussy, Villejuif, France.

About FIGHT-202

The FIGHT-202 open-label, multicenter study (NCT02924376) is evaluating the safety and efficacy of pemigatinib (INCB54828), Incyte’s investigational, selective, potent, oral fibroblast growth factor receptor (FGFR) inhibitor in adult (age ≥ 18 years) patients with advanced/metastatic or surgically unresectable cholangiocarcinoma with known fibroblast growth factor (FGF)/FGFR alterations and who have failed at least one previous treatment.

Patients were enrolled into one of three cohorts – Cohort A (FGFR2 translocations), Cohort B (other FGF/FGFR genetic alterations [GA]) or Cohort C (no FGF/FGFR GAs). 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, C and A plus B, progression free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR) and safety.

The FIGHT-202 study is fully recruited outside of Japan, and updated data are expected to be presented in the second half of 2019. For more information about FIGHT-202, visit View Source

About FIGHT

Phase 2 studies investigating the safety and efficacy of pemigatinib monotherapy across several FGFR-driven malignancies are ongoing—the FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program currently comprises FIGHT-201 in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 alterations; FIGHT-202 in patients with metastatic or surgically unresectable cholangiocarcinoma who have failed previous therapy, including with activating FGFR2 translocations; and FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 translocations. FIGHT-302, a randomized Phase 3 trial in newly-diagnosed patients with cholangiocarcinoma and activating FGFR2 translocations, is expected to be initiated before the end of 2018 (NCT03656536).

About FGFR and Pemigatinib (INCB54828)

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 mutations, 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.

On October 21, 2018 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported results from an integrated analysis of the pivotal Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials that showed the investigational personalized medicine entrectinib shrank tumors (objective response rate; ORR) in more than half (57.4 percent) of people with neurotrophic tropomyosin receptor kinase (NTRK) fusion-positive solid tumors. Objective responses to entrectinib were seen across 10 different solid tumor types (median duration of response [DoR] = 10.4 months), including in people with and without central nervous system (CNS) metastases at baseline. Importantly, entrectinib shrank tumors that had spread to the brain in over half of people (intracranial response; IC ORR=54.5 percent), with more than a quarter of these people having a complete response (Press release, Genentech, OCT 21, 2018, View Source [SID1234530008]). The safety profile of entrectinib was consistent with that seen in previous analyses.

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"These data demonstrate the potential of entrectinib to treat a range of difficult-to-treat and rare cancers regardless of their site of origin," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Entrectinib has the potential to redefine personalized medicine, which can utilize tests such as next-generation sequencing to find the right treatment for each individual patient. People with NTRK fusion-positive solid tumors need more options, and we look forward to working with health authorities to bring this potential treatment to patients as soon as possible."

Genentech is leveraging its expertise in developing personalized medicines and advanced diagnostics, in conjunction with Foundation Medicine, to develop a novel diagnostics approach using next-generation sequencing that will help identify people with NTRK gene fusions likely to benefit from entrectinib.

Entrectinib has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumors in adult and pediatric patients who have either progressed following prior therapies or have no acceptable standard therapies. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible.

These NTRK fusion-positive results will be presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in Munich, Germany on Sunday, October 21, 2018 from 11:24–11:36 a.m. CEST (Abstract LBA17; Hall B3 – Room 22). Follow Genentech on Twitter via @Genentech and keep up to date with ESMO (Free ESMO Whitepaper) 2018 Congress news and updates by using the hashtag #ESMO2018.

Genentech also recently presented positive results at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC) that showed entrectinib shrank tumors (ORR) in 77.4 percent of people with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). In addition, entrectinib demonstrated a durable response of more than two years (DoR = 24.6 months). Importantly, entrectinib was shown to shrink tumors in more than half of people with cancer in the CNS (IC ORR: 55.0 percent). The safety profile of entrectinib was consistent with that seen in previous analyses.

Genentech plans to submit results from these integrated analyses to global health authorities for the treatment of NTRK fusion-positive solid tumors and ROS1-positive NSCLC.

About the integrated analysis

The integrated analysis included data from 54 people with locally advanced or metastatic NTRK fusion-positive solid tumors (10 tumor types, >19 histopathologies) from the Phase II STARTRK-2, Phase I STARTRK-1 and Phase I ALKA-372-001 trials. The studies enrolled people across 15 countries and more than 150 clinical trial sites. Tumor types evaluated in the studies to date included breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.

STARTRK-2 is a Phase II, global, multicenter, open-label basket study in people with solid tumors that harbor an NTRK1/2/3, ROS1 or ALK-positive gene fusion. The primary endpoint is ORR, and DoR is a secondary endpoint. Other secondary outcome measures include time to response, clinical benefit rate, intracranial tumor response, progression-free survival (PFS), CNS PFS and overall survival (OS).
STARTRK-1 is a Phase I, multicenter, open-label dose escalation study of a daily continuous dosing schedule in people with solid tumors with NTRK1/2/3, ROS1 or ALK gene fusions in the U.S. and South Korea. The trial assessed the safety and tolerability of entrectinib via a standard dose escalation scheme and determined the recommended Phase II dose.
ALKA-372-001 is Phase I, multicenter, open-label dose escalation study of an intermittent and continuous entrectinib dosing schedule in people with advanced or metastatic solid tumors with TRKA/B/C, ROS1 or ALK gene fusions in Italy.
Overall, entrectinib was well tolerated and the majority of adverse events were Grade 1-2, reversible, and managed with treatment interruption or dose reduction. Treatment-related adverse events leading to discontinuation occurred in 3.9 percent of patients. The most common treatment-related adverse events were altered sense of taste (dysgeusia), fatigue and dizziness.

About entrectinib

Entrectinib (RXDX-101) is an investigational, oral medicine in development for the treatment of locally advanced or metastatic solid tumors that harbor NTRK1/2/3 or ROS1 gene fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer. Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions. Entrectinib is being investigated across a range of solid tumor types, including breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.

About NTRK gene fusions

Neurotrophic tyrosine receptor kinase (NTRK) fusion-positive cancer occurs when the NTRK1/2/3 genes fuse with other genes, resulting in altered TRK proteins (TRKA/TRKB/TRKC) that can activate signaling pathways involved in proliferation of certain types of cancer. NTRK gene fusions are tumor-agnostic, meaning they are present in tumors irrespective of site of origin. These fusions have been identified in a broad range of solid tumor types, including breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers. There is a high unmet medical need for treatments for people with life-threatening and hard-to-treat NTRK fusion-positive tumors.

On October 21, 2018 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical stage targeted oncology company, reported the completed stage 1 safety and efficacy data from the ongoing Phase 1b clinical trial of single agent sitravatinib in patients with certain classes of oncogenic mutations (Press release, Mirati, OCT 21, 2018, View Source [SID1234530009]). The data for a cohort of patients harboring CBL mutations were presented in a proffered poster session (oral presentation) on Sunday, October 21st, 2018, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in Munich, Germany.

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"For patients whose tumors are driven by the CBL mutation, there are limited viable treatment options," said Charles M. Baum, M.D., Ph.D., President and Chief Executive Officer, Mirati Therapeutics, Inc. "Our sitravatinib single agent program will focus on NSCLC and melanoma patients with CBL inactivating mutations, who we believe could benefit most from single agent sitravatinib therapy."

Update from Sitravatinib Single Agent Study with CBL Inactivating Mutations

The presentation provided an update from the pre-planned expansion cohort of the Phase 1b clinical trial of single agent sitravatinib in patients with CBL inactivating mutations. Eight patients were evaluable as of the data cut-off on August 27, 2018.

In the subset of evaluable NSCLC patients, 1/2 confirmed partial responses were observed with 2/2 patients experiencing tumor regression.

In the subset of evaluable melanoma patients, 1/2 confirmed partial responses in evaluable patients were observed with 1/2 patients experiencing tumor regression.

In the subset of evaluable patients with other solid tumors, 2/4 had stable disease with 2/4 experiencing tumor regression.
CBL mutations are present in 1.5% of NSCLC, 3.5% of melanoma, and 2% of cancers of unknown origin.

About Sitravatinib

Sitravatinib is a spectrum-selective kinase inhibitor that potently inhibits receptor tyrosine kinases (RTKs), including TAM family receptors (TYRO3, Axl, Mer), split family receptors (VEGFR2, KIT) and RET. As an immuno-oncology agent, sitravatinib is being evaluated in combination with nivolumab (OPDIVO), an anti-PD-1 checkpoint inhibitor, in patients who have experienced documented disease progression following treatment with a checkpoint inhibitor. Sitravatinib’s potent inhibition of TAM and split family RTKs may overcome resistance to checkpoint inhibitor therapy through targeted reversal of an immunosuppressive tumor microenvironment, enhancing antigen-specific T cell response and expanding dendritic cell-dependent antigen presentation.

Sitravatinib is also being evaluated as a single agent in a Phase 1b expansion clinical trial enrolling patients whose tumors harbor specific mutations in the CBL kinase. When CBL is inactivated by mutation, multiple RTKs, including TAM, VEGFR2 and KIT, are dysregulated and may act as oncogenic tumor drivers in NSCLC and melanoma. Sitravatinib potently inhibits these RTKs and is being investigated as a treatment option for cancer patients with CBL mutations.

On October 21, 2018 Genmab A/S (Nasdaq Copenhagen: GEN) reported the study met its primary endpoint for Part 1 of the Phase III CASSIOPEIA study (MMY3006) of daratumumab in combination with bortezomib, thalidomide and dexamethasone (VTD) versus VTD alone as frontline treatment for patients who are candidates for autologous stem cell transplant (ASCT) (Press release, Genmab, OCT 21, 2018, View Source [SID1234530041]). The first part of the study met the primary endpoint of number of patients that achieved a sCR, which was reported in 28.9% of patients treated with daratumumab in combination with VTD, compared to 20.3% of patients who received VTD alone with an odds ratio of 1.60 (95% CI: 1.21 – 2.12, p ≤ 0.001). In the second part of the study, all responders have been re-randomized to receive either maintenance treatment with daratumumab monotherapy or observation (no treatment).

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Overall, the safety profile of daratumumab in combination with VTD is consistent with the known safety profile of the VTD regimen used in patients receiving ASCT and the known safety profile for daratumumab.

Further analysis of the safety and efficacy data is ongoing and Janssen Biotech, Inc., which licensed daratumumab from Genmab in 2012, will discuss the potential for regulatory submissions for this indication with health authorities and IFM/HOVON plans to submit additional data for presentation at an upcoming medical conference and for publication in a peer-reviewed journal.

"Having previously seen positive data in the ALCYONE trial, for the frontline treatment of patients ineligible for autologous stem cell transplant, we are very pleased to see the results from the CASSIOPEIA study, which presents exciting insights into the potential of daratumumab for newly diagnosed multiple myeloma patients who received an autologous stem cell transplantation (ASCT). We also look forward to the data from the second part of the study, which will provide further data on the impact of daratumumab monotherapy as maintenance treatment," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Today’s news does not impact Genmab’s 2018 financial guidance.

About the CASSIOPEIA (MMY3006) study
This Phase III study is a randomized, open-label, multicenter study, run by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen Biotech, Inc., including 1,085 newly diagnosed subjects with previously untreated symptomatic multiple myeloma who are eligible for high dose chemotherapy and stem cell transplant. In the first part of the study, patients were randomized to receive induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide (an immunomodulatory agent) and dexamethasone (a corticosteroid) or bortezomib, thalidomide and dexamethasone alone. The primary endpoint is the number of patients that achieve a sCR. In the second part of the study, patients that achieved a response will undergo a second randomization to either receive maintenance treatment of daratumumab 16 mg/kg every 8 weeks for up to 2 years versus no further treatment (observation). The primary endpoint of this part of the study is progression free survival (PFS).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 30,770 new patients are expected to be diagnosed with multiple myeloma and approximately 12,770 people are expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX(daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,7,8,9,10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma, myelodysplastic syndromes, B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.

On October 21, 2018 Incyte Corporation (Nasdaq:INCY) reported its updated data from its ongoing Phase 2 FIGHT-202 trial evaluating pemigatinib (INCB54828), its selective fibroblast growth factor receptor (FGFR) inhibitor, in patients with advanced/metastatic or surgically unresectable cholangiocarcinoma (bile duct cancer) who failed at least one previous treatment (Press release, Incyte, OCT 21, 2018, View Source [SID1234530010]). In patients with FGFR2 translocations who were followed for at least eight months, interim study results demonstrated an overall response rate (ORR) of 40 percent, the primary endpoint, and a median progression free survival (PFS) of 9.2 months, a key secondary endpoint.

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These results are being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress in Munich, Germany in a poster presentation on Sunday, October 21 from 12:45 p.m. CEST to 1:45 p.m. CEST (6:45 a.m. ET to 7:45 a.m. ET). (Location: Hall A3 – Poster Area Networking Hub; Abstract #756P)

"We are pleased to share updated interim results from our ongoing FIGHT-202 trial at ESMO (Free ESMO Whitepaper), which underscore the potential of pemigatinib as an effective new treatment option for patients with advanced cholangiocarcinoma who have FGFR2 translocations," said Steven Stein, M.D., Chief Medical Officer, Incyte. "If the full data set warrant it, we look forward to submitting our new drug application to the FDA in 2019, seeking approval of pemigatinib as a first-in-class selective FGFR inhibitor to treat patients with advanced cholangiocarcinoma, a devastating disease."

Cholangiocarcinoma is a cancer that arises from the cells within the bile ducts. It is often diagnosed late (stages III and IV) and the prognosis is poor. It is most common in those over 70 years old and is more common in men than women. FGFR2 fusion genes are drivers of the disease – occurring almost exclusively in patients with intrahepatic cholangiocarcinoma (iCCA), a subset of the disease – and are found in up to 20 percent of iCCA patients. The incidence of cholangiocarcinoma with FGFR2 translocation is increasing and is currently estimated at 2,500-3,000 patients in the U.S., Europe and Japan.

Key Findings from FIGHT-202

Updated, longer-term follow-up data from the interim analysis presented today at ESMO (Free ESMO Whitepaper) (data cut as of July 24, 2018) show that in patients with advanced/metastatic or surgically unresectable iCCA with FGFR2 translocations treated with pemigatinib who had at least eight months of follow up (Cohort A, n=47), the combined overall response rate (ORR) was 40 percent, including 19 (40 percent) patients with confirmed partial responses and 21 (45 percent) patients with stable disease (SD). The combined disease control rate (DCR) was 85 percent (40/47). Additionally, median progression free survival (PFS) was 9.2 months and median overall survival (OS) was 15.8 months.

Pemigatinib was well-tolerated. The most common treatment-emergent adverse events (TEAEs) were hyperphosphatemia (61 percent), alopecia (42 percent), diarrhea (39 percent), decreased appetite (37 percent) and fatigue (36 percent). Grade ≥3 TEAEs (observed >5 percent of patients) were hypophosphatemia (14 percent), hyponatremia (8 percent), abdominal pain (7 percent) and arthralgia (7 percent). Five patients had TEAEs with a fatal outcome, none of which were related to study treatment.

"I am extremely encouraged by the interim results of the FIGHT-202 study, which demonstrated meaningful clinical activity and promising preliminary progression-free survival estimates, and, as a practicing clinician, I am excited about the potential of pemigatinib to provide a new treatment option for my patients suffering from the life-threatening nature of advanced cholangiocarcinoma," said Antoine Hollebecque, M.D., Institut de Cancérologie Gustave Roussy, Villejuif, France.

About FIGHT-202

The FIGHT-202 open-label, multicenter study (NCT02924376) is evaluating the safety and efficacy of pemigatinib (INCB54828), Incyte’s investigational, selective, potent, oral fibroblast growth factor receptor (FGFR) inhibitor in adult (age ≥ 18 years) patients with advanced/metastatic or surgically unresectable cholangiocarcinoma with known fibroblast growth factor (FGF)/FGFR alterations and who have failed at least one previous treatment.

Patients were enrolled into one of three cohorts – Cohort A (FGFR2 translocations), Cohort B (other FGF/FGFR genetic alterations [GA]) or Cohort C (no FGF/FGFR GAs). 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, C and A plus B, progression free survival (PFS), overall survival (OS), duration of response (DOR), disease control rate (DCR) and safety.

The FIGHT-202 study is fully recruited outside of Japan, and updated data are expected to be presented in the second half of 2019. For more information about FIGHT-202, visit View Source

About FIGHT

Phase 2 studies investigating the safety and efficacy of pemigatinib monotherapy across several FGFR-driven malignancies are ongoing—the FIGHT (FIbroblast Growth factor receptor in oncology and Hematology Trials) clinical trial program currently comprises FIGHT-201 in patients with metastatic or surgically unresectable bladder cancer, including with activating FGFR3 alterations; FIGHT-202 in patients with metastatic or surgically unresectable cholangiocarcinoma who have failed previous therapy, including with activating FGFR2 translocations; and FIGHT-203 in patients with myeloproliferative neoplasms with activating FGFR1 translocations. FIGHT-302, a randomized Phase 3 trial in newly-diagnosed patients with cholangiocarcinoma and activating FGFR2 translocations, is expected to be initiated before the end of 2018 (NCT03656536).

About FGFR and Pemigatinib (INCB54828)

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 mutations, 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.