On September 28, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it will present new data at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 congress, the results of a number of studies in patients receiving Alecensa (alectinib) for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, SEP 28, 2019, View Source [SID1234539877]).

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"The data presented at ESMO (Free ESMO Whitepaper) this year further demonstrate the well-established benefits of Alecensa, and confirm its use as the standard of care for newly diagnosed advanced or metastatic ALK-positive lung cancer patients," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "The positive results from our real-world data study further support the benefits we have seen from our Phase III clinical studies."

Real-world data results in patients with ALK-positive NSCLC
Insights utilising real-world data from the Flatiron Health database will be presented at the congress on Saturday 28 September (Abstract #1546P, 12:00 CEST). These data further support the benefits of Alecensa in the real-world setting, where real-world progression free survival (rwPFS), time to treatment discontinuation (TTD – used as a surrogate for real-world treatment duration) and overall survival (OS) were demonstrated to be longest in Alecensa treated patients with previously untreated ALK-positive NSCLC. The results also show that despite the established benefit of individual ALK inhibitors (ALKi) as first-line therapies and the inclusion of ALKi in many clinical guidelines, as recently as 2017 and 2018 more than 25% of patients with ALK-positive NSCLC received a non-ALKi as first-line therapy. Data were available for 620 patients with ALK-positive advanced NSCLC.

1L, first-line therapy; ALKi, ALK inhibitor; rwPFS, real-world progression-free survival; TTD, time to treatment discontinuation; OS, overall survival; NR, not reached (median survival estimate could not be calculated). 6 & 12-month probability is the event-free survival probability for the following events: progression, treatment discontinuation and death at 6 months and at 12 months, respectively.

Final PFS and updated Phase III ALEX data
Final PFS and updated results from the pivotal Phase III ALEX study, to be presented on Sunday 29 September during a poster discussion (Abstract #1484PD, 16:30 CEST), confirm the superior efficacy and tolerability of Alecensa in comparison to crizotinib in patients with untreated ALK-positive NSCLC, reducing the risk of disease worsening or death by 57% (hazard ratio [HR]=0.43, 95% CI: 0.32–0.58). Mature data show that Alecensa provides a median investigator-assessed progression free survival (PFS) of nearly three years (34.8 months, 95% CI: 17.7-not reached [NR]) versus 10.9 months (95% CI: 9.1–12.9) in those who received crizotinib.

Alecensa also demonstrated superior efficacy compared to crizotinib regardless of the presence of central nervous system (CNS) metastases at baseline. For those with CNS metastases, the median investigator-assessed PFS was 25.4 months for Alecensa versus 7.4 months for crizotinib (HR=0.37, 95% CI: 0.23–0.58). In those without CNS metastases, it was 38.6 months versus 14.8 months respectively (HR=0.46, 95% CI: 0.31–0.68). Despite longer median treatment duration with Alecensa versus crizotinib (27.7 months versus 10.8 months), the safety profile for Alecensa remains favourable; fewer Alecensa-treated patients experienced Grade 3–5 adverse events (AEs) (48.7% versus 55.0% crizotinib).

BFAST
On Monday 30 September (08:30 – 10:00 CEST, Abstract LBA81), Roche will also present results from the first cohort of the Phase II/III Blood First Assay Screening Trial (BFAST). BFAST is the first prospective trial to use blood-based next generation sequencing (NGS) as the sole method of identifying and assigning NSCLC patients to targeted therapy based on actionable genetic alterations without the need for tissue biopsy. The study utilised FoundationOne Liquid, Foundation Medicine’s liquid (blood) biopsy assay to detect fusions in circulating tumour DNA (ctDNA) from a simple blood draw to identify ALK status and consequently eligibility for Alecensa.

About the ALEX Study
ALEX (NCT02075840/B028984) is a randomised, multicentre, open-label, Phase III study evaluating the efficacy and safety of Alecensa versus crizotinib in treatment-naïve patients with ALK-positive NSCLC whose tumours were characterised as ALK-positive by the VENTANA ALK (D5F3) CDx Assay, a companion immunohistochemistry (IHC) test developed by Roche Tissue Diagnostics. Patients were randomised (1:1) to receive either Alecensa or crizotinib. The primary endpoint of the ALEX study was PFS as assessed by the investigator, and secondary endpoints include: Independent Review Committee (IRC)-assessed PFS, time to CNS progression, objective response rate (ORR), duration of response (DOR) and OS. The multicentre study was conducted in 303 people across 161 sites in 31 countries. OS data continue to be considered immature.

About the real-world data Study
The real-world data study is a retrospective cohort study that utilised US electronic health record data from Flatiron Health, a nationwide database containing de-identified patient-level structured and unstructured data, curated via technology-enabled abstraction. Treatment patterns and outcomes, including real-world progression free survival (rwPFS) and overall survival (OS) were extracted for first- or second-line therapy. Time to treatment discontinuation (TTD) was used as a surrogate for real-world treatment duration accounting for treatment beyond progression. Time-to-event analyses were performed using Kaplan-Meier methods. Patients included were diagnosed with stage IIIB-IV ALK-positive NSCLC between 01 January 2011 and 30 September 2018. Data were available for 620 patients with ALK-positive advanced NSCLC. An ALKi was given to 420/620 (67.7%) patients as first-line therapy.

About Alecensa
Alecensa (RG7853/AF-802/RO5424802/CH5424802) is a highly selective, CNS active, oral medicine created at Chugai Kamakura Research Laboratories and is being developed for people with NSCLC whose tumours are identified as ALK-positive. ALK-positive NSCLC is often found in younger people who have a light or non-smoking history. It is almost always found in people with a specific type of NSCLC called adenocarcinoma. Alecensa is now approved in 83 countries as an initial (first-line) treatment for ALK-positive, metastatic NSCLC, including in the US, Europe, Japan and China.

About Roche in lung cancer
Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have five approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease.

On September 28, 2019 GlaxoSmithKline plc (LSE/NYSE: GSK) reported results from PRIMA (ENGOT-OV26/GOG-3012), the Phase 3 randomised, double-blind, placebo-controlled study of Zejula (niraparib) as a maintenance therapy in women with first-line ovarian cancer following a response to platinum-based chemotherapy (Press release, GlaxoSmithKline, SEP 28, 2019, View Source [SID1234539878]). Niraparib treatment resulted in a 38% reduction in the risk of disease progression or death in the overall population (PFS, HR 0.62; 95% CI, 0.50–0.75; p<0.001).

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These results were driven by a clinically meaningful reduction in risk of progression in women with:

BRCA mutation tumours (risk reduction of 60%, HR 0.40 (95% CI, 0.27–0.62) p<0.001).
HR-deficient BRCA wild type tumours (risk reduction of 50%, HR 0.50 (95% CI, 0.30–0.83), p=0.006).
HR-proficient tumours (risk reduction of 32%, HR 0.68 (95% CI, 0.49–0.94), p=0.020).
The PRIMA study enrolled patients with a response to their first-line treatment with platinum-based chemotherapy including those with high risk of disease progression, a population with high unmet need and previously under-represented in first-line ovarian cancer studies.

Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK said: "Ovarian cancer is the eighth most commonly occurring cancer in women worldwide and women with this devastating disease have a five-year survival rate of less than 50%. PRIMA is a landmark study as we believe these data have the potential to fundamentally change how women with ovarian cancer are treated."

In an interim analysis of overall survival (OS), niraparib also demonstrated an encouraging trend toward improvement in OS relative to placebo. A pre-planned interim analysis of OS numerically favoured niraparib in the overall population (HR 0.70; 95% CI 0.44-1.11). In the HR-deficient subgroup, 91% of women on niraparib were alive at 24 months vs. 85% for placebo (HR=0.61; 95% CI, 0.27-1.40). These data are not yet mature, and the significance is not fully known. The OS interim analysis also showed 81% of women receiving niraparib in the HR-proficient subgroup were alive at 24 months vs. 59% of women receiving placebo (HR=0.51; 95% CI, 0.27-0.97).

Dr. Antonio Gonzalez, co-director, department of medical oncology, Clinica Universidad de Navarra, and Primary Investigator for PRIMA said: "The PRIMA study demonstrated the importance of maintenance therapy and the benefit that niraparib provided to women with ovarian cancer. I believe that niraparib monotherapy after surgery and platinum-based chemotherapy could be an important new treatment option for patients."

Niraparib is not currently approved in the first-line ovarian cancer maintenance setting. GSK will share these data with the relevant health authorities and is on track to file by the end of the year.

The safety profile demonstrated in PRIMA did not differ from the established safety profile. The most common grade 3 or higher adverse events with niraparib included anaemia (31%), thrombocytopenia (29%), and neutropenia (13%). Implementation of an individualised dosing regimen based on body weight and/or platelet count reduced the incidence of haematological treatment-emergent adverse events. No new safety signals were identified. Validated patient reported outcomes indicate quality of life was similar between the niraparib and placebo treatment arms.

Niraparib is marketed in the United States and Europe under the trade name Zejula.

About PRIMA
PRIMA is a double-blind, randomised Phase 3 study designed to evaluate niraparib versus placebo in first-line Stage III or IV ovarian cancer patients. The study assessed the efficacy of niraparib as maintenance treatment, as measured by progression free survival. Patients with a response to first-line platinum chemotherapy were randomised 2:1 to niraparib or placebo. The trial was amended to include an individualised niraparib starting dose of 200 mg once-daily in patients with baseline weight <77kg and/or platelet count <150K/μL and 300 mg in all other patients.

About Zejula (niraparib)
Niraparib is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.

Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in three pivotal trials. GSK is building a robust niraparib franchise by assessing activity across multiple tumour types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development programme for niraparib includes a Phase 3 trial as first-line monotherapy maintenance treatment in patients with first-line ovarian cancer (the PRIMA trial), a Phase 3 study as a first-line triplet maintenance treatment in ovarian cancer (FIRST), a Phase 3 trial for the treatment of patients with germline BRCA-mutated, metastatic breast cancer (the BRAVO trial), and a Phase 2 study of niraparib combined with bevacizumab maintenance treatment in advanced ovarian cancer (OVARIO).

Several combination studies are also underway, including trials of niraparib plus pembrolizumab in metastatic, triple-negative breast cancer and advanced, platinum-resistant ovarian cancer (the TOPACIO trial). Janssen Biotech has licensed rights to develop and commercialise niraparib specifically for patients with prostate cancer worldwide, except in Japan.

Important Safety Information for ZEJULA
Myelodysplastic Syndrome/Acute Myeloid Leukaemia (MDS/AML), including some fatal cases, was reported in 1.4% of patients receiving ZEJULA vs 1.1% of patients receiving placebo in Trial 1 (NOVA), and 0.9% of patients treated with ZEJULA in all clinical studies. The duration of ZEJULA treatment in patients prior to developing MDS/AML varied from <1 month to 2 years. All patients had received prior chemotherapy with platinum and some had also received other DNA damaging agents and radiotherapy. Discontinue ZEJULA if MDS/AML is confirmed.

Haematologic adverse reactions (thrombocytopenia, anaemia and neutropenia) have been reported in patients receiving ZEJULA. Grade ≥3 thrombocytopenia, anaemia and neutropenia were reported in 29%, 25%, and 20% of patients receiving ZEJULA, respectively. Discontinuation due to thrombocytopenia, anaemia, and neutropenia occurred, in 3%, 1%, and 2% of patients, respectively. Do not start ZEJULA until patients have recovered from haematological toxicity caused by prior chemotherapy (≤ Grade 1). Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment, and periodically thereafter. If haematological toxicities do not resolve within 28 days following interruption, discontinue ZEJULA, and refer the patient to a haematologist for further investigations.

Hypertension and hypertensive crisis have been reported in patients receiving ZEJULA. Grade 3-4 hypertension occurred in 9% of patients receiving ZEJULA vs 2% of patients receiving placebo in Trial 1, with discontinuation occurring in <1% of patients. Monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of the ZEJULA dose, if necessary.

Based on its mechanism of action, ZEJULA can cause foetal harm. Advise females of reproductive potential of the potential risk to a foetus and to use effective contraception during treatment and for 6 months after receiving their final dose. Because of the potential for serious adverse reactions from ZEJULA in breastfed infants, advise lactating women to not breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.

In clinical studies, the most common adverse reactions (Grades 1-4) in ≥10% of patients included: thrombocytopenia (61%), anaemia (50%), neutropenia (30%), leukopenia (17%), palpitations (10%), nausea (74%), constipation (40%), vomiting (34%), abdominal pain/distention (33%), mucositis/stomatitis (20%), diarrhoea (20%), dyspepsia (18%), dry mouth (10%), fatigue/asthenia (57%), decreased appetite (25%), urinary tract infection (13%), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation (10%), myalgia (19%), back pain (18%), arthralgia (13%), headache (26%), dizziness (18%), dysgeusia (10%), insomnia (27%), anxiety (11%), nasopharyngitis (23%), dyspnoea (20%), cough (16%), rash (21%) and hypertension (20%).

Common lab abnormalities (Grades 1-4) in ≥25% of patients included: decrease in haemoglobin (85%), decrease in platelet count (72%), decrease in white blood cell count (66%), decrease in absolute neutrophil count (53%), increase in AST (36%) and increase in ALT (28%).

About Ovarian Cancer
Approximately 300,000 women are diagnosed with ovarian cancer each year. Ovarian cancer is the eighth most frequent cause of cancer death among women. Despite high response rates to platinum-based chemotherapy in the second-line advanced treatment setting, approximately 85% of patients will experience recurrence within two years. Late-line treatment options for patients with ovarian cancer are few, with the proportion of patients achieving an overall response typically less than 10% when treated with chemotherapy.

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On September 28, 2019 Immunomedics, Inc. (NASDAQ: IMMU) ("Immunomedics" or the "Company"), a leading biopharmaceutical company in the area of antibody-drug conjugates (ADC), reported at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress interim data from the 100-patient cohort of cisplatin-eligible patients of the Company’s TROPHY-U-01 open-label Phase 2 study (Press release, Immunomedics, SEP 28, 2019, View Source [SID1234539913]). In this interim report, sacituzumab govitecan produced an overall response rate (ORR) of 29 percent in 35 patients with metastatic urothelial cancer (mUC) who have relapsed or are refractory to immune checkpoint inhibitors (CPI) and platinum-based chemotherapy.

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"Patients with mUC who have cancer progression after platinum-based and CPI therapy have poor outcomes and limited treatment options. Together with the prior clinical data, I believe the favorable benefit/risk profile of sacituzumab govitecan has the potential to change the treatment landscape of UC," commented Dr. Scott T. Tagawa, the Richard A. Stratton Associate Professor in Hematology and Oncology, Associate Professor of Clinical Medicine and of Clinical Urology, member of the Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, who presented the interim results from TROPHY-U-01 at the ESMO (Free ESMO Whitepaper) 2019 Annual Congress in Barcelona, Spain.

The 29 percent ORR included two confirmed complete responses, six confirmed partial responses (PRs) and two additional PRs pending confirmation. At the time of data cutoff on August 5, 2019, eight of ten responders have ongoing response. Median time to onset of response was 1.5 months (range, 1.2-2.8). For patients with liver metastases, ORR was 25 percent.

"These interim results, in a larger number of CPI-experienced patients, are consistent with previously reported efficacy of sacituzumab govitecan in mUC, and also show encouraging benefits observed in patients relapsed on enfortumab vedotin," stated Dr. Behzad Aghazadeh, Executive Chairman of Immunomedics. "Based on these data, the Company will be exploring registrational pathways with the FDA."

Consistent with the Company’s previous observations, sacituzumab govitecan was well tolerated with a predictable safety profile. Treatment-related Grade 3 and 4 adverse events were mostly hematologic and gastrointestinal related, including neutropenia (54%) and diarrhea (9%). Importantly, there were no grade 2 or above neuropathy or rash, no interstitial lung disease, and no treatment-related deaths.

New Clinical Collaborations to Advance Sacituzumab Govitecan to Early-Line Treatment of Breast Cancer

In addition, the Company announced two clinical collaborations that address continuing unmet needs in breast cancer. The collaboration with Roche will evaluate the safety and efficacy of the combination of atezolizumab (Tecentriq), a programmed cell death ligand 1 (PD-L1)-blocking checkpoint inhibitor, and sacituzumab govitecan, as a frontline treatment of patients with metastatic or inoperable locally advanced TNBC.

"We are pleased to be partnering with Roche, a global leader in breast cancer therapy," said Dr. Aghazadeh. "With a favorable efficacy and safety profile, we believe sacituzumab govitecan is a strong combination partner and could provide an improved therapeutic option in earlier lines of therapy when combined with immune checkpoint inhibitors."

The open-label, multicenter, randomized Phase 1b/2 study will be conducted as part of MORPHEUS, Roche’s novel cancer immunotherapy development platform. Patients with newly-diagnosed mTNBC will be randomized to receive the combination of atezolizumab and sacituzumab govitecan or nab-paclitaxel plus atezolizumab as standard of care. MORPHEUS is a Phase 1b/2 adaptive platform to develop combinations of cancer immunotherapies more rapidly and efficiently. Roche will be responsible for conducting the randomized trial.

Further, Immunomedics and the GBG Forschungs-GmbH (GBG), Neu-Isenburg, Germany, have entered into a collaboration to develop sacituzumab govitecan as a treatment for newly-diagnosed breast cancer patients who do not achieve a pathological complete response (pCR) following standard neoadjuvant therapy.

"While pCR is now widely accepted as a very strong surrogate endpoint for event-free and distant disease-free survival (DDFS) in high-risk breast cancer, for patients who do not achieve a pCR following standard neoadjuvant therapy, the risk for developing metastatic disease is very high," said Professor Dr. med. Sibylle Loibl, MD, PhD, Chief Executive Officer of GBG. "We are very excited to be the first cooperative group worldwide to evaluate sacituzumab govitecan in this early stage of breast cancer treatment."

According to the medical literature, depending on the hormone receptor status, about 40% to 70% of HER2-negative breast cancer patients treated with neoadjuvant therapy do not achieve a pCR.1 For these patients, with the exception of those with the HER2-positive subtype, there is currently no approved standard of care, leaving them at high risk of distant relapse of their disease.

"We are extremely pleased to partner with GBG, the world-renowned cooperative group, to launch this exciting study which will introduce sacituzumab govitecan to breast cancer patients at an early stage of their disease," commented Dr. Aghazadeh. "We look forward to working closely with GBG to study the potential benefits of sacituzumab govitecan in a significantly larger population of breast cancer patients who have few viable alternatives today."

The multinational, post-neoadjuvant Phase 3 SASCIA study developed by GBG will be conducted under the sponsorship of GBG. Approximately 1,200 high-risk patients with newly-diagnosed HER2-negative breast cancer not achieving a pCR following standard neoadjuvant therapy will be randomized to receive either sacituzumab govitecan or treatment of physician’s choice. Primary endpoint is invasive DFS (iDFS) with overall survival, patient reported outcome/quality of life, circulating tumor DNA clearance, and safety serving as secondary endpoints.

"Given the high level of Trop-2 expression in breast cancer, we are hopeful that sacituzumab govitecan will be established as a new treatment standard for those high-risk patients who failed standard treatment," remarked Professor Dr. med. Frederik Marmé, MD, PhD, Section Lead for Gynecological Oncology, University Medical Center, Mannheim, Germany, and designated Principal Investigator of the SASCIA trial.

BLA Resubmission Timeline Update

Based on the remaining activities for compilation of the BLA, and preparations for a pre-approval inspection, the Company revised its re-submission guidance from early fourth quarter to the late November or early December timeframe.

Reference

Untch M, Jackisch C, et al. Nab-Paclitaxel Improves Disease Free Survival in Early Breast Cancer: GBG 69-GeparSepto. J Clin Oncol. 2019 September 1;37:2226-2234.
About Sacituzumab Govitecan

Sacituzumab govitecan, Immunomedics’ most advanced product candidate, is a novel, first-in-class antibody-drug conjugate (ADC) delivering SN-38, a potent topoisomerase I inhibitor, directly to tumor cells by targeting the Trop-2 antigen expressed by many solid cancers. Based on encouraging Phase 1/2 results, the U.S. Food and Drug Administration has granted sacituzumab govitecan Breakthrough Therapy Designation for the treatment of patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease.

On September 28, 2019 GlaxoSmithKline plc (LSE/NYSE: GSK) reported GSK3359609, an inducible T cell co-stimulatory (ICOS) agonist antibody designed to selectively enhance T cell function, showed promising anti-tumour activity in combination with pembrolizumab in PD-1/L1 naive patients with head and neck squamous cell carcinoma (HNSCC) (Press release, GlaxoSmithKline, SEP 28, 2019, View Source [SID1234539879]). Findings from the INDUCE-1 study also suggested GSK3359609 has single agent activity in patients with PD-1/L1 experienced HNSCC.

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The safety and tolerability profile of GSK3359609 was consistent with the results reported in the dose escalation phase of INDUCE-1. The data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2019 in Barcelona, Spain.

Dr. Axel Hoos, Senior Vice President and Head Oncology R&D, said: "Immunotherapies such as GSK3359609 are a critical part of our oncology pipeline and we are encouraged by the INDUCE-1 data demonstrating the potential of this agent to enhance anti-tumour activity beyond what PD-1 blockade alone has demonstrated. The clinical responses observed are encouraging and, based on precedent with CTLA-4 or PD-1, we aim to demonstrate the main effect of our ICOS agonist to be on improving survival for patients, which requires further study. Based on these results, we are initiating the INDUCE-3 registrational trial to investigate the potential survival benefit of GSK3359609 with pembrolizumab in first-line recurrent/metastatic HNSCC for patients who are PD-L1 positive."

The data presented stem from the expansion phase of INDUCE-1, a first-in-human, open-label study investigating GSK3359609 as a monotherapy and in combination with other regimens. Patients in the study had recurrent or metastatic HNSCC and had received up to five prior lines of therapy in the advanced setting. Patients in the monotherapy cohort had previously been treated with PD-1/L1 therapy and received 1 mg/kg GSK3359609. Patients in the combination cohort were naive to PD-1/L1 therapy and received 0.3 mg/kg GSK3359609 and 200 mg pembrolizumab. Patients in both cohorts were evaluated until disease progression or unacceptable toxicity, for up to two years.

In the 34 evaluable patients who received the combination therapy, the overall response rate was 24% (n=8; 95% CI: 11, 58.7). Responses in the combination cohort were durable with all responding patients maintaining benefit for 6 months or longer (median not reached; 95% CI: 4.2 months, NR); the median progression-free survival (PFS) was 5.6 months (95% CI: 2.4, 7.4). Of the 21 patients with known PD-L1 expression data, the majority of responders and patients with stable disease had PD-L1 score below 20. Of the 16 evaluable patients who received monotherapy, the overall response rate was 6% (n=1; 95% CI: 0.2, 30.2).

The INDUCE-1 study was conducted pursuant to an agreement between GSK and Merck & Co, Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the U.S. and Canada). GSK is continuing its relationship with MSD to support the INDUCE-3 phase II/III combination trial to be initiated by the end of 2019.

HNSCC is a cancer that develops from squamous cells in the mucous membranes of the mouth, nose and throat, and is the seventh most common cancer worldwide with approximately 600,000 new cases diagnosed each year.[i] Although HNSCC occurs more frequently in men in their 50s or 60s, the incidence is increasing among younger individuals.[ii] HNSCC tumours are highly immunogenic and have an elevated expression of immune checkpoint modulators, including ICOS and PD-1.[iii]

GSK3359609 Clinical Development Programme
The clinical development programme for GSK3359609 looks to investigate the anti-tumour potential of targeting the ICOS receptor through an agonist antibody alone and in combination with other immune checkpoint therapies for the treatment of a range of tumour types.

GSK3359609 is not currently approved for use anywhere in the world.

GSK in Oncology
GSK is focused on maximising patient survival through transformational medicines. GSK’s pipeline is focused on immuno-oncology, cell therapy, cancer epigenetics and synthetic lethality. Our goal is to achieve a sustainable flow of new treatments based on a diversified portfolio of investigational medicines utilising modalities such as small molecules, antibodies, antibody drug conjugates and cells, either alone or in combination.

On September 27, 2019 Incyte (Nasdaq:INCY) reported updated results, including the final result for the primary endpoint, from its 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 (Press release, Incyte, SEP 27, 2019, View Source [SID1234539849]). 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.

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These results are being presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress in Barcelona, Spain during a late-breaking oral session today, September 27, from 3:00 p.m. CEST to 3:15 p.m. CEST (9:00 a.m. EDT to 9:15 a.m. EDT) in Madrid Auditorium (Hall 2); Abstract #LBA40.

"We are excited to share updated data for pemigatinib, which may provide a promising and targeted treatment approach for patients with cholangiocarcinoma harboring FGFR2 fusions or rearrangements," said Peter Langmuir, M.D., Group Vice President, Targeted Therapeutics, Incyte. "Patients with advanced cholangiocarcinoma face a poor prognosis, and currently there is no standard of care beyond first-line chemotherapy. We are committed to advancing pemigatinib, a potent and selective therapy targeting a key driver of this disease, and plan to submit the New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) shortly."

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.1,2 The incidence of cholangiocarcinoma varies regionally and ranges between 0.3 – 3.4 per 100,000 in North America and Europe.1 FGFR2 fusions or rearrangements occur almost exclusively in iCCA, where they are observed in 10-16 percent of patients.3-5

Key Findings from FIGHT-202

Updated data presented today 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

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.

"Patients with cholangiocarcinoma face a significant challenge as they cope with a life-threatening condition that is often diagnosed once it has progressed into late stages," said Arndt Vogel, M.D., Senior Consultant and Professor at Hannover Medical School. "As a physician, I am encouraged to see the data from the FIGHT-202 study, which demonstrate the potential that pemigatinib has to become an important and much needed targeted treatment option for this patient population."

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 View Source

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. 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.

Conference Call Information

Incyte will host an investor conference call and webcast at 11:00 a.m. EDT (5:00 p.m. CEST) today, September 27, 2019—the call and webcast can be accessed via the Events and Presentations tab of the Investor section of www.incyte.com and it will be available for replay for 30 days.

To access the conference call, please dial 877-407-3042 for domestic callers or +1 201-389-0864 for international callers. When prompted, provide the conference identification number, 13694537.