Published Late Breaking Abstracts at ESMO 2018: Sunday 21st October


More than 60 Late Breaking Abstracts (LBA’s) are scheduled to be published at this year’s European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (E.S.M.O 2018). Below you will find the 27 published at the sessions on Sunday 21st October, the third day of the conference and the busiest for Late Breaking Abstracts.

For full analysis identifying new technologies, drugs, targets, start-ups etc. we recommend Commercial Interest at E.S.M.O Annual Meeting 2018: Analytical Tool.

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Roche’s investigational personalised medicine entrectinib shrank tumours in people with NTRK fusion-positive solid tumours

On October 21, 2018 Roche (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 personalised medicine entrectinib shrank tumours (objective response rate; ORR) in more than half (57.4%) of people with neurotrophic tropomyosin receptor kinase (NTRK) fusion-positive solid tumours (Press release, Hoffmann-La Roche, OCT 21, 2018, View Source [SID1234530312]). Objective responses to entrectinib were seen across ten different solid tumour types (median duration of response [DOR]=10.4 months), including in people with and without central nervous system (CNS) metastases at baseline.[1]
Importantly, entrectinib shrank tumours that had spread to the brain in over half of people (intracranial response; IC ORR=54.5%), with more than a quarter of these people having a complete response.[1] The safety profile of entrectinib was consistent with that seen in previous analyses.[1]

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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, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "Entrectinib has the potential to redefine personalised 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 tumours need more options, and we look forward to working with health authorities to bring this potential treatment to patients as soon as possible."

Roche is leveraging its expertise in developing personalised 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.[2;3]

Entrectinib has been granted Breakthrough Therapy Designation (BTD) by the US Food and Drug Administration (FDA); Priority Medicines (PRIME) designation by the European Medicines Agency (EMA); and Sakigake designation by the Japanese health authorities for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or have no acceptable standard therapies.[4] These designations are reserved for medicines that demonstrate substantial improvements over existing therapies or where there are unmet medical needs.
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 21 October 2018, 11:24-11:36 am CEST (LBA17). Follow Roche on Twitter via @Roche and keep up to date with ESMO (Free ESMO Whitepaper) 2018 congress news and updates by using the hashtag #ESMO2018.

Roche also recently presented positive results at the IASLC 19th World Conference on Lung Cancer (WCLC) that showed entrectinib shrank tumours (ORR) in 77.4% of people with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).[5] In addition, entrectinib demonstrated a durable response of more than two years (DOR=24.6 months).[5] Importantly, entrectinib was shown to shrink tumours in more than half of people with cancer in the CNS (IC ORR=55.0%).[5] The safety profile of entrectinib was consistent with that seen in previous analyses.[5]

Roche plans to submit results from these integrated analyses to global health authorities for the treatment of NTRK fusion-positive solid tumours 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 tumours (10 tumour types, >19 histopathologies) from the phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA-372-001 trials.[1] The studies enrolled people across 15 countries and more than 150 clinical trial sites. Tumour types evaluated in the studies to date included breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.

STARTRK-2 is a phase II, global, multicentre, open-label basket study in people with solid tumours that harbour an NTRK1/2/3, ROS1 or ALK-positive gene fusion.[6] The primary endpoint is ORR and DOR is a secondary endpoint.[6] Other secondary outcome measures include time to response, clinical benefit rate, intracranial tumour response, progression-free survival (PFS), CNS PFS and overall survival (OS).[6]
STARTRK-1 is a phase I, multicentre, open-label dose escalation study of a daily continuous dosing schedule in people with solid tumours with NTRK1/2/3, ROS1 or ALK gene fusions in the US and South Korea.[7] The trial assessed the safety and tolerability of entrectinib via a standard dose escalation scheme and determined the recommended phase II dose.[7]
ALKA-372-001 is a phase I, multicentre, open-label dose escalation study of an intermittent and continuous entrectinib dosing schedule in people with advanced or metastatic solid tumours with TrkA/B/C, ROS1 or ALK gene fusions in Italy.[8]
Overall, entrectinib was well tolerated and the majority of adverse events were Grade 1-2, reversible, and managed with treatment interruption or dose reduction.[1] Treatment-related adverse events leading to discontinuation occurred in 3.9% of patients.[1] The most common treatment-related adverse events were altered sense of taste (dysgeusia), fatigue, and dizziness.[1]

About entrectinib
Entrectinib (RXDX-101) is an investigational, oral medicine in development for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3 or ROS1 gene fusions. It is a selective, CNS-active 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.[2;3] Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions.[2;3] Entrectinib is being investigated across a range of solid tumour types, including breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.[6-8]

Entrectinib has been granted Breakthrough Therapy Designation (BTD) by the US Food and Drug Administration (FDA); Priority Medicines (PRIME) designation by the European Medicines Agency (EMA); and Sakigake designation by the Japanese health authorities for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or have no acceptable standard therapies.[4]

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 signalling pathways involved in proliferation of certain types of cancer. NTRK gene fusions are tumour-agnostic, meaning they are present in tumours irrespective of site of origin, and have been identified a broad range of solid tumour types, including breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.[1] There is a high unmet medical need for treatments for people with life-threatening NTRK fusion-positive tumours.

Updated data showed that Roche’s Tecentriq in combination with Avastin shrank tumours in people with unresectable or advanced hepatocellular carcinoma (HCC)

On October 21, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it will present updated data from a Phase Ib study evaluating Tecentriq (atezolizumab) in combination with Avastin (bevacizumab) as a treatment for people with unresectable or advanced hepatocellular carcinoma (HCC), the most common form of liver cancer (Press release, Hoffmann-La Roche, OCT 21, 2018, View Source [SID1234530311]).

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The efficacy-evaluable population was comprised of all patients who have received the combination treatment and who have been followed on the study for a minimum of 16 weeks; the median survival follow-up was 7 months. Among the efficacy-evaluable patients, the objective response rate (ORR) was 32% (23 of 73 patients) as assessed by investigator (INV) per RECIST v1.1, 27% (20 of 73 patients) as assessed by independent review facility (IRF) per RECIST v1.1 and 34% (25 of 73 patients) as assessed by IRF per HCC mRECIST.

Complete responses were seen in 1 (1%) patient as assessed by INV per RECIST v1.1, 4 (5%) patients by IRF per RECIST v1.1 and 8 (11%) patients as assessed by IRF per HCC mRECIST. The disease control rate (DCR) was consistent across all forms of assessment, with 77% (56 of 73) of patients assessed by INV per RECIST v1.1 and 75% (55 of 73) as assessed by both IRF per RECIST v1.1 and IRF per HCC mRECIST, experiencing a response or stable disease.

Responses were observed in all assessed patient subgroups, including aetiology, region, baseline alpha-fetoprotein levels and tumour burdens (extrahepatic spread (EHS) and macrovascular invasion (MVI)). Median duration of response (DOR) and overall survival (OS) have not yet been reached.

"We’re pleased to present updated data from our combination of Tecentriq and Avastin at ESMO (Free ESMO Whitepaper) in unresectable or advanced hepatocellular carcinoma, an aggressive disease that takes the lives of hundreds of thousands of people worldwide each year," said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development. "We are encouraged by these results, particularly the durability of response, and we look forward to sharing updated results in the future".

In the safety-evaluable population (n=103), 27% of patients (28 of 103) experienced Grade 3-4 treatment-related adverse events and 2% of patients (2 of 103) experienced treatment-related Grade 5 adverse events. No new safety signals related to the combination therapy were identified beyond the established safety profiles for the individual medicines.

The late-breaking Phase Ib study data will be presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper). Abstract (oral) LBA26 October 21st CEST 11:00-12:30: Hall A1, Room 17.

In July, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for Tecentriq in combination with Avastin as a first-line treatment for people with advanced or metastatic HCC, based on the totality of data from this ongoing Phase Ib study. 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 can access them as soon as possible. This is one of 23 Breakthrough Therapy Designations for Roche’s portfolio of medicines and the 3rd for Tecentriq.

Earlier this year, Roche initiated IMbrave150 (NCT03434379), a multicentre, randomised, open-label Phase III study investigating the combination of Tecentriq and Avastin versus sorafenib in people with unresectable or advanced HCC. This study is currently enrolling. Further information about the trial can be found on clinicaltrials.gov.

Efficacy and safety results

a The efficacy-evaluable population was comprised of all patients who have received the combination treatment and who have been followed on the study for a minimum of 16 weeks; the median survival follow-up was 7 months.

b ORR INV per RECIST v1.1 was the primary endpoint in protocol 5, when patients included in this analysis were enrolled.

c Data from 4 patients (6%) not evaluable or missing

d PFS data are very immature, based on a median follow up of 7 months and subject to change.

ORR, objective response rate CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; DCR, disease control rate; DOR, duration of response; PFS, progression free survival; NR, not reached; +, censored value.

About Hepatocellular Carcinoma (HCC)
Liver cancer is the sixth most common cancer, with over 800,000 new cases diagnosed annually.[1] It is the fourth most common cause of cancer deaths globally,[1] and HCC represents approximately 90% of all cases of primary liver cancer.[2] HCC develops predominantly in those people with cirrhosis due to chronic hepatitis B or C.[3] Despite the prevalence of HCC, outcomes for unresectable or advanced HCC remain limited, with few systemic therapeutic options,[4] and a median survival of approximately 6-20 months following diagnosis.[5]

About the Phase Ib study (NCT02715531)
This Phase Ib, open-label, multicentre study is evaluating the safety and clinical activity of a number of cancer immunotherapy combinations in different solid tumours, including Tecentriq and Avastin in patients with unresectable or advanced HCC (Arm A). Participants in Arm A receive Tecentriq (1200 mg) and Avastin (15 mg/kg) intravenously (IV) every three weeks until loss of clinical benefit or unacceptable toxicity. The primary objectives of Arm A, as of the latest protocol, are to assess the clinical activity, based on ORR assessment by IRF per RECIST v1.1 and to assess the safety and tolerability of the combination. Secondary efficacy endpoints include ORR by INV assessed per RECIST v1.1 and IRF assessed per HCC mRECIST, as well as PFS, DOR and OS. As tumour volume in the liver can also be assessed by discriminating between arterially-enhanced and not vascularised areas, the HCC-specific mRECIST criteria were developed to take this aspect into account and to judge how the liver responds to therapy.
Note: ORR INV per RECIST v1.1 was the primary endpoint in protocol 5, when patients included in this analysis were enrolled.

About IMbrave150 (NCT03434379)
IMbrave150 is a Phase III, multicentre, randomised, open-label study enrolling approximately 480 people with unresectable or advanced HCC 2:1 to receive the combination of Tecentriq and Avastin or sorafenib. Tecentriq will be administered IV, 1200mg on day 1 of each 21-day cycle and Avastin will be administered IV, 15mg/kg on day 1 of each 21-day cycle. Sorafenib will be administered by mouth, 400mg twice per day, on days 1-21 of each 21-day cycle. Participants will receive the combination or sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Co-primary endpoints are OS and ORR by IRF per RECIST v1.1. Secondary endpoints include additional efficacy parameters as measured by INV assessed per RECIST v1.1, IRF assessed per RECIST v1.1 and IRF assessed per HCC mRECIST.

About the Tecentriq (atezolizumab) and Avastin (bevacizumab) combination
There is a strong scientific rationale to support the use of Tecentriq and Avastin in combination. The Tecentriq and Avastin regimen may enhance the potential of the immune system to combat a broad range of cancers. Avastin, in addition to its established anti-angiogenic effects, may further enhance Tecentriq’s ability to restore anti-cancer immunity, by inhibiting vascular endothelial growth factor (VEGF)-related immunosuppression, promoting T-cell tumour infiltration and enabling priming and activation of T-cell responses against tumour antigens.

About Tecentriq (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1 expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq has the potential to be used as a foundational combination partner with cancer immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers.

Tecentriq is already approved in the European Union, United States and more than 70 countries for people with previously treated metastatic NSCLC and for certain types of untreated or previously treated metastatic urothelial carcinoma (mUC).

About Avastin (bevacizumab)
Avastin is a prescription-only medicine that is a solution for intravenous infusion. It is a biologic antibody designed to specifically bind to a protein called VEGF that plays an important role throughout the lifecycle of the tumour to develop and maintain blood vessels, a process known as angiogenesis. Avastin is designed to interfere with the tumour blood supply by directly binding to the VEGF protein to prevent interactions with receptors on blood vessel cells. The tumour blood supply is thought to be critical to a tumour’s ability to grow and spread in the body (metastasize).

LSK BioPharma and Jiangsu Hengrui Medicine Announce Global Clinical Collaboration to Evaluate the Combination of Anti-Angiogenesis and Immuno-Oncology Therapy for Patients with Advanced Hepatocellular Carcinoma (HCC)

On October 21, 2018 LSK BioPharma (or "LSKB"), a US-based biopharmaceutical firm and Jiangsu Hengrui Medicine, Co., Ltd. (SHA:600276, or "Hengrui"), one of the largest and most innovative fully-integrated biopharmaceutical companies based in China, reported that the companies have entered into a global clinical collaboration in patients with advanced hepatocellular carcinoma (HCC), evaluating the safety and efficacy of LSKB’s rivoceranib, also known as apatinib or Aitan (brand name) in China, a selective and potent VEGFR-2 inhibitor, in combination with Hengrui’s camrelizumab (SHR-1210), a humanized anti-PD-1 monoclonal antibody currently under NDA review in China for classic Hodgkin’s Lymphoma (cHL) (Press release, LSK BioPharma, OCT 21, 2018, View Source [SID1234530127]).

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Under the terms of the clinical collaboration agreement, Hengrui will be responsible for administering the clinical trial with all study costs outside of China shared equally among both parties. LSKB will retain full commercial rights for rivoceranib outside of China and Hengrui will retain full commercial rights for camrelizumab worldwide.

"At diagnosis, hepatocellular carcinoma typically has a dismal prognosis due to a lack of treatment options and the ineffectiveness of standard systemic therapies," said Dr. Sung Chul Kim, LSKB’s President, "we are enthusiastic to work with Hengrui for the potential to help more patients by combining rivoceranib with camrelizumab."

"We are pursuing camrelizumab in about 20 clinical trials in China. There is ample scientific evidence and preliminary clinical data supporting the synergistic effects of camrelizumab when used in combination with apatinib (rivoceranib)," said Dr. Lianshan Zhang, President of Global R&D of Hengrui. "We look forward to partnering with LSKB to build upon the existing preclinical and clinical data and further explore this combination therapy for patients with hepatocellular carcinoma, an area of high unmet medical needs."

"As one of the leading biopharmaceutical companies in China, we are committed to developing innovative medicines to address the urgent clinical needs. Through years of effort, Hengrui has built a robust oncology pipeline, which holds significant potential to benefit cancer patients. We are excited about this collaboration to accelerate the delivery of effective and durable treatment options for patients around the world," said Dr. Piaoyang Sun, Chairman of Hengrui.

Currently, Hengrui is conducting an open-label, single arm multicenter phase 2 study (NCT03463876) to evaluate the efficacy and safety of the combination of camrelizumab and apatinib in patients with advanced HCC in China, where Hengrui has received approval of apatinib monotherapy for advanced gastric cancer. At ASCO (Free ASCO Whitepaper) 2018, it was reported that the objective response rate (ORR) and disease control rate (DCR) were 50.0% and 85.7%, respectively, among 14 evaluated advanced HCC patients treated by camrelizumab in combination with apatinib in an open-label, phase 1 study in China (Xu et al., NCT02942329). In addition, camrelizumab and apatinib combination therapy is also being evaluated by Hengrui for multiple indications including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and gastric cancer (GC) in China.

It is hypothesized that the combination of rivoceranib and camrelizumab may enhance the immune system, aiding the fight against cancer. In addition to the known anti-angiogenic effects of rivoceranib, it may also enhance camrelizumab’s anti-tumor activity by normalizing tumor vasculature and reversing the tumor suppressive immune microenvironment.

About Rivoceranib (Apatinib)
Rivoceranib, also known as apatinib or Aitan (brand name) in China, is the first successful small-molecule angiogenesis inhibitor in gastric cancer. Rivoceranib acts by inhibiting angiogenesis, a critical process in cancer growth and proliferation. Specifically, rivoceranib selectively inhibits VEGFR-2 which mediates the primary pathway for tumor-mediated angiogenesis.

Hengrui, who owns the China rights to rivoceranib, received the approval from China National Medical Products Administration (NMPA, formerly known as CFDA) in 2014 to market the drug under the brand name Aitan in China for advanced gastric cancer. LSKB, which holds the global rights (ex-China), is currently conducting a global (12 countries including US, Japan, Korea, Italy, Germany, and Russia) phase 3 clinical trial of rivoceranib in advanced or metastatic gastric cancer patients. Rivoceranib (apatinib) is currently listed in 220 clinical studies on www.clinicaltrials.gov with over 20,000 patients enrolled or planned to be enrolled in numerous cancers including GC, colorectal cancer (CRC), HCC, NSCLC, esophageal cancer, thyroid cancer, mesothelioma, and neuroendocrine tumors. It has also shown potential to significantly improve outcomes in combination with chemotherapeutics and immunotherapy, as well as for maintenance therapy. LSKB has received notification designating rivoceranib as an orphan medicinal product for the treatment of gastric cancer from the European Commission in the European Union, the US FDA, as well as the MFDS in South Korea.

Rivoceranib was developed by Advenchen Laboratories in Southern California under the designation YN968D1. The compound was exclusively licensed to Hengrui in China (2005) and LSKB (2008) for rest of the world.

About Camrelizumab (SHR-1210)

Camrelizumab (SHR-1210) is an investigational humanized monoclonal antibody recognizing the programmed death-1 (PD-1) receptor. Camrelizumab functions as an immune checkpoint inhibitor by specifically blocking the interaction between PD-1 and PD-L1 and reversing the immunosuppressive signal of PD-1 on the T cell. Approximately 20 clinical trials on camrelizumab in multiple indications including lung cancer, liver cancer, gastric cancer, esophageal cancer, nasopharyngeal carcinoma, lymphoma, melanoma and other advanced solid tumors are being conducted in China and Australia as monotherapy or in combination with other therapeutic agents. A marketing application for camrelizumab for relapsed/refractory classic Hodgkin’s Lymphoma was submitted by Hengrui to China NMPA, which was accepted in April 2018, and is currently under review.

Incyte Announces Positive Interim Data from Phase 2 Trial of Pemigatinib, Its Selective FGFR Inhibitor, in Patients with Cholangiocarcinoma

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.