On October 19, 2018 Incyte (NASDAQ:INCY) reported Phase 2 preliminary results of the GEOMETRY mono-1 clinical trial of investigational MET inhibitor capmatinib in 94 adult patients with advanced non-small cell lung cancer (NSCLC) harboring MET exon-14 skipping mutations (Press release, Incyte, OCT 19, 2018, View Source [SID1234529977]). The GEOMETRY mono-1 study showed an overall response rate (ORR) of 72.0 percent (95% CI: 50.6-87.9) in treatment-naive patients and 39.1 percent (95% CI: 27.6-51.6) in previously treated patients. ORR was assessed by blinded independent review committee (BIRC). Adverse events (AEs) were consistent with previously reported data and no new safety signals were observed.

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Results of the Novartis-sponsored Phase 2 study were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress (October 19, 2018 at 4:45 p.m. CEST / 10:45 a.m. EDT, Abstract LBA52).1

"These preliminary findings reveal the potential of capmatinib in MET exon-14 skipping mutated NSCLC patients. Compared to the previously treated patient groups, the primary advantage in terms of overall response rate reported in treatment-naive patients highlights the clinical relevance for an earlier diagnostic testing and prompt treatment of this challenging patient population," said Juergen Wolf, M.D., University Hospital Cologne, Germany.

NSCLC is the most common type of lung cancer, impacting more than 2 million people per year.2 Approximately 3-4 percent of all patients with NSCLC have an identified MET mutation.3 Though rare, this mutation is an indicator of especially poor prognosis and there is currently no approved therapy designed to target this mutation.4

"We are very pleased to announce these promising, preliminary results for capmatinib, another investigational medicine invented at Incyte that has the potential to be the first MET-selective targeted agent approved by the FDA," said Steven Stein, M.D., Chief Medical Officer, Incyte. "We are encouraged by the results of this study and the potential for capmatinib to help patients with advanced MET mutated NSCLC, who face a poor prognosis and represent a clear unmet medical need."

About GEOMETRY mono-1

The GEOMETRY mono-1 trial is a multicenter, open-label, Phase 2 study to evaluate the efficacy and safety of single-agent capmatinib (INC280) in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring MET amplification and/or mutations. Patients with MET exon-14 skipping were assigned to Cohorts 4 (previously treated patients) or 5B (treatment naive) regardless of MET amplification/gene copy number (centrally confirmed), and received 400 mg capmatinib tablets twice daily. The primary endpoint was ORR based on BIRC assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) by BIRC. The GEOMETRY mono-1 study found an ORR in the treatment-naive patients (n=25) of 72.0 percent (95% CI: 50.6-87.9) and an ORR in the previously treated patients (n=69) of 39.1 percent (95% CI: 27.6-51.6). DOR was not reached by the time of analysis, indicating sustainability of response.1,6

The most common treatment-related AEs included peripheral edema, nausea, vomiting and increased blood creatinine levels. Of patients treated with capmatinib, 83.8 percent experienced an AE, with 33.1 percent having grade 3/4 AEs.1,6

About Capmatinib

Capmatinib (INC280) is an investigational, oral and selective MET inhibitor invented at Incyte that was licensed to Novartis in 2009. Under the Agreement, Incyte granted Novartis exclusive development and commercialization worldwide rights to this MET inhibitor compound and certain back-up compounds in all indications. Novartis has stated that it expects to submit a new drug application to the U.S. Food and Drug Administration for capmatinib as a treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring MET amplification and/or mutations in 2019. If capmatinib is successfully developed by Novartis, Incyte may become eligible for over $500 million in future milestones as well as royalties of between 12 percent and 14 percent on global sales by Novartis.

On October 19, 2018 Novartis reported Phase II preliminary results of the GEOMETRY mono-1 clinical trial of investigational MET inhibitor capmatinib (INC280) in 94 adult patients with advanced non-small cell lung cancer (NSCLC) harboring MET exon-14 skipping mutations (Press release, Novartis, OCT 19, 2018, View Source [SID1234529978]). The GEOMETRY mono-1 study showed an overall response rate (ORR) of 72.0% (95% CI: 50.6-87.9) in treatment-naive patients and 39.1% (95% CI: 27.6-51.6) in previously treated patients. ORR was assessed by blinded independent review committee (BIRC). Adverse events (AEs) were consistent with previously reported data and no new safety signals were observed. Results of the Phase II study were presented today at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress [October 19, 2018 at 4:45 PM CET] (Abstract #LBA52)[1].

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"These preliminary findings reveal the potential of capmatinib in MET exon-14 skipping mutated NSCLC patients. Compared to the previously treated patient groups, the primary advantage in terms of overall response rate reported in treatment-naive patients highlights the clinical relevance for an earlier diagnostic testing and prompt treatment of this challenging patient population," said Juergen Wolf, MD, University Hospital Cologne.

NSCLC is the most common type of lung cancer, impacting more than 2 million people per year[2]. Approximately 3-4% of all patients with NSCLC have an identified MET mutation[3]. Though rare, this mutation is an indicator of especially poor prognosis and there is currently no approved therapy designed to target this mutation[4].

"Patients diagnosed with advanced MET mutated NSCLC represent an unmet medical need and often face a poor prognosis," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "We are encouraged by the GEOMETRY mono-1 results and the potential for capmatinib to help patients with this disease."

About GEOMETRY mono-1
The GEOMETRY mono-1 trial is a multicenter, open-label, phase II study to evaluate the efficacy and safety of single-agent INC280 in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring MET amplification and/or mutations. Patients with MET exon-14 skipping were assigned to Cohorts 4 (previously treated patients) or 5B (treatment naive) regardless of MET amplification/gene copy number (centrally confirmed), and received 400 mg capmatinib tablets twice daily. The primary endpoint was ORR based on BIRC assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) by BIRC. The GEOMETRY mono-1 study found an ORR in the treatment-naive patients (n=25) of 72.0% (95% CI: 50.6-87.9) and an ORR in the previously treated patients (n=69) of 39.1% (95% CI: 27.6-51.6). DOR was not reached by the time of analysis, indicating sustainability of response[1],[6].

The most common treatment-related AEs included peripheral edema, nausea, vomiting, and increased blood creatinine levels. Of patients treated with INC280, 83.8% experienced an AE, with 33.1% having grade 3/4 AEs[1],[6].

Capmatinib (INC280) is an investigational, oral and selective MET inhibitor licensed to Novartis by Incyte Corporation in 2009. Under the Agreement, Incyte granted Novartis exclusive Development and Commercialization worldwide rights to this MET inhibitor compound and certain back-up compounds in all indications.

Novartis Commitment to Lung Cancer
Worldwide, lung cancer causes more deaths than colon, breast and prostate cancer combined, and over 2 million new cases of lung cancer are diagnosed each year[2]. Among patients with NSCLC, almost 70% have an actionable mutation that may be targeted with available therapies[7]. To determine the most appropriate treatment, medical organizations recommend genomic testing for patients with lung cancer[8].

Novartis Oncology’s research in NSCLC has helped transform treatment approaches for patients living with mutation-driven diseases, among others. Novartis continues its commitment to the global lung cancer community through ongoing studies, as well as the exploration of investigational compounds that target genetic biomarkers in NSCLC.

On October 19, 2018 BioLineRx Ltd. (NASDAQ: BLRX) (TASE:BLRX), a clinical-stage biopharmaceutical company focused on oncology and immunology, reported top-line results from the dual combination arm of the Phase 2a COMBAT/KEYNOTE-202 study, evaluating patients with metastatic pancreatic adenocarcinoma (PDAC) treated with BL-8040 in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside of the United States and Canada) (Press release, BioLineRx, OCT 19, 2018, View Source;p=irol-newsArticle&ID=2372469 [SID1234529979]). The results show encouraging disease control and extended overall survival, particularly in patients undergoing second-line treatment. The data, entitled, "A Phase 2a Trial to Assess the Safety and Efficacy of BL-8040 and Pembrolizumab in Patients with Metastatic Pancreatic Adenocarcinoma (PDAC)," will be presented on October 20, 2018 at 5:15 pm CET at the immuno-oncology poster discussion session co-chaired by the principal investigator of the study at the European Society for Medical Oncology 2018 Congress, which is being held October 19-23, in Munich, Germany.

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The study included 37 patients with metastatic PDAC who had disease progression after one or more previous lines of treatment. Study treatment consisted of an initial 5-day priming period of BL-8040 monotherapy, followed by repeated 3-week cycles of BL-8040 in combination with KEYTRUDA. In addition to clinical efficacy assessments, the study included a number of pharmacodynamic assessments to support BL-8040’s mechanism of action as an immuno-oncology agent.

The data show that the treatment regimen was safe and well tolerated. The disease control rate (patients exhibiting a response or stable disease) was 34.5% for the evaluable population (N=29), including 1 patient (3.4%) with a partial response showing a 40% reduction in tumor burden, as well as 9 patients (31%) with stable disease, with a median treatment time of 72 days (37-267). Median overall survival (OS) in all patients (N=37) was 3.3 months with a 6-month survival rate of 34.4%. A significant observation was made in the subpopulation of patients receiving the study drugs as a second-line treatment (N=17), where the median overall survival was 7.5 months, with a 6-month survival rate of 51.5%. This compares favorably with historical median overall survival data of 6.1 months for the only currently approved second-line PDAC treatment (a chemotherapy combination of Onivyde, 5-FU and leucovorin).

The clinical activity correlates with previously announced partial pharmacodynamic results from the BL-8040 monotherapy period of this study, in which BL-8040 induced infiltration of T-cells into the core and periphery of metastatic lesions. Additional in-depth analyses of biopsies taken at screening and following monotherapy or combination treatment of BL-8040 and KEYTRUDA have now been completed and will be presented at the poster discussion session tomorrow, Saturday, October 20, 2018. Immediately following the presentation and lifting of the embargo on publication of the data, the Company will report these additional results in a press release.

Prof. Manuel Hidalgo, MD, PhD, Professor of Medicine at Harvard Medical School, Chief of Hematology Oncology and Co-Director, Pancreatic Cancer Research Program, at Beth Israel Deaconess Hospital, and principal investigator of this study, said, "Metastatic pancreatic cancer remains an area of very high unmet medical need, as currently approved treatments are limited by poor response rates and survival. Despite recent advances in cancer treatment with immune checkpoint inhibitors in many tumor types, pancreatic cancer remains refractory to these treatment options. It is therefore encouraging to see that the combination of BL-8040 and KEYTRUDA shows promising clinical activity, a robust pharmacodynamic effect and a very good safety and tolerability profile. I look forward to the next phase of this study, in which chemotherapy will be added to the combination of BL-8040 and KEYTRUDA in an expansion cohort. I believe that the addition of chemotherapy may boost the clinical response rate, while hopefully maintaining the favorable safety and tolerability profile observed in this arm of this trial."

"We are extremely pleased with the top-line results from this ongoing study," stated Philip Serlin, Chief Executive Officer of BioLineRx. "These data, which demonstrate that the combination of BL-8040 and KEYTRUDA is safe, with encouraging signs of clinical activity and proof of concept for the mechanism of action, support the combination’s potential to become an effective immunotherapy regimen for pancreatic cancer – a disease that has responded very poorly to available treatments, including immunotherapy. We look forward to expanding our collaboration with MSD and maximizing the potential of this combination through an additional study arm that will add chemotherapy to the regimen. We believe the addition of chemotherapy may be synergistic with the existing combination, as chemotherapy has been shown to reduce overall tumor burden while inducing immunogenic cell death, leading to activation and expansion of new tumor-reactive T-cells. Based on its demonstrated mechanism of action, we believe BL-8040 can facilitate the infiltration of these T-cells into the tumor core, alongside the restoration of T-cell activity within the tumor by KEYTRUDA. We look forward to commencing the triple combination arm of this important study by the end of this year, with results expected in the second half of 2019."

About the COMBAT/KEYNOTE-202 Study

The Phase 2a COMBAT/KEYNOTE-202 study is currently an open-label, multicenter, single-arm trial designed to evaluate the safety and efficacy of the combination of BL-8040 and KEYTRUDA (pembrolizumab), an anti-PD-1 therapy marketed by Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada), in over 30 subjects with metastatic pancreatic adenocarcinoma. The study is primarily designed to evaluate the clinical response, safety and tolerability of the combination of these therapies, and is being carried out in the US, Israel and additional territories. The study is being conducted by BioLineRx under a collaboration agreement signed in 2016 between BioLineRx and MSD, through a subsidiary, to support a Phase 2a program investigating BioLineRx’s BL-8040 in combination with KEYTRUDA in patients with metastatic pancreatic cancer.

In July 2018, the Company announced the expansion of its immuno-oncology collaboration with MSD to include a triple combination arm investigating the safety, tolerability and efficacy of BL-8040, KEYTRUDA and chemotherapy. The triple combination arm will focus on second-line pancreatic cancer patients. Thirty to fifty patients will be enrolled in this arm, planned for initiation in the fourth quarter of 2018.

BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in several clinical trials to be a robust mobilizer of immune cells to peripheral blood and to be effective at inducing direct tumor cell death. In addition, clinical findings have demonstrated the ability of BL-8040 to mediate infiltration of T-cells into tumors that were previously immunologically "cold" and devoid of immune cell infiltrate. Immune checkpoint inhibitors (such as KEYTRUDA) produce anti-cancer effects by increasing the activity of T-cells through blockade of the interaction between the immune checkpoint receptor PD-1, on T-cells, and its ligand PD-L1, on tumor cells. Pancreatic cancers have very little T-cell infiltrate, making them less susceptive to checkpoint blockade than other tumors that are infiltrated by T-cells. Therefore, combining BL-8040 with immune checkpoint blockade is predicted to increase the responsiveness of pancreatic cancer patients to immunotherapy. Further increase in the sensitivity of pancreatic cancer cells to BL-8040 and KEYTRUDA may be achieved by chemotherapy-mediated immunogenic cell death and exposure of new tumor antigens, resulting in activation of new anti-cancer T cell clones.

About BL-8040

BL-8040 is a short synthetic peptide for the treatment of hematological malignancies, solid tumors, and stem cell mobilization. It functions as a high-affinity best-in-class antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells and immune-cells, sensitization of cancer cells to chemo- and bio-based anti-cancer therapies, and direct anti-cancer effect by inducing programmed cell death (apoptosis). BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

On October 19, 2018 Idera Pharmaceuticals, Inc. (NASDAQ: IDRA), a clinical-stage biopharmaceutical company focused on the development and ultimate commercialization of drug candidates for both oncology and rare disease indications characterized by small, well-defined patient populations with serious unmet needs, reported its data from the ongoing ILLUMINATE-204 trial investigating tilsotolimod, Idera’s intratumorally-delivered toll-like receptor 9 (TLR9) agonist, in combination with ipilimumab (Yervoy*) at the 2018 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Idera Pharmaceuticals, OCT 19, 2018, View Source [SID1234529980]).

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The poster, which was selected for a poster discussion session, highlighted additional analyses of data for 21 patients for whom efficacy and safety analysis were originally presented at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting this past June (data cut-off May 9th).

The new analyses address the potential of intramural tilsotolimod to induce an antitumor response in combination with ipilimumab in injected tumors as well as uninjected tumors via an abscopal effect. As previously reported the overall response rate (ORR, by RECIST 1.1) for these 21 patients was 39%. Notably, in 7 of the 8 responders tumor shrinkage was observed in both the injected and uninjected tumors. Tumor shrinkage at uninjected lesions was observed in an additional four patients who had not met the criteria for RECIST v.1.1 response status as of this analysis.

Clinical responses were seen in patients whose HLA-ABC RNA (MHC class I) expression is low at baseline. Rodig and colleagues1 have recently shown that robust MHC class I expression is required for anti-CTLA-4 activity. Our findings suggest that combining tilsotolimod with ipilimumab may overcome this resistance mechanism, and therefore, enhance clinical activity and increase the overall response rate compared to that expected with ipilimumab monotherapy.

The ILLUMINATE-204 trial is enrolling two distinct patient populations, both patients who are naïve to ipilimumab therapy (N=40; Primary Efficacy Endpoint Population) and patients who have prior ipilimumab experience (N=Up to 20; Secondary Efficacy Endpoint Population). Of the initial 21 patients available for efficacy evaluations 6 of 17 patients from the Primary Efficacy Endpoint Population and 2 of 4 patients from the Secondary Efficacy Endpoint Population achieved RECIST v.1.1 responses, further demonstrating a signal that tilsotolimod has the potential to help overcome prior ipilimumab resistance.

"The data presented at ESMO (Free ESMO Whitepaper) demonstrate that in patients with melanoma progressing on or after PD-1 inhibitor therapy, injecting a single tumor lesion with tilsotolimod, in combination with ipilimumab, produced tumor shrinkage in distant uninjected lesions in nearly all patients with reported responses by RECIST v1.1 criteria," stated Adi Diab, M.D., Lead Trial Investigator, Assistant Professor, Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas, MD Anderson Cancer Center. "Moreover, clinical responses were seen in tumors where MHC class I expression was low at baseline. In a recent clinical study in melanoma, it was shown that robust MHC class I expression is required for anti-CTLA-4 activity. Our findings suggest that combining tilsotolimod with ipilimumab may overcome this mechanism of resistance to anti-CTLA-4 monotherapy."

"The clear demonstration of tumor shrinkage in uninjected tumors following the injection of a single tumor lesion with tilsotolimod, provides clinical confirmation of our translational data and addresses an important frequently asked question," stated Joanna Horobin, Idera’s Chief Medical Officer. "Additionally, the new observation that tilsotolimod may overcome the requirement for MHC class 1 expression for effective anti-tumor therapy with ipilimumab in patients otherwise unlikely to respond, is a very exciting finding and addresses another important question regarding the contribution of tilsotolimod when given in combination with ipilimumab."

The poster discussion is scheduled for Saturday, October 20, 2018 at 2:45 PM CEST (8:45 AM EST) in Room ICM-14b at the Messe Munchen Congress Center in Munich, Germany.

In addition to the poster discussion, the company also presented a Trials in Progress (TiPS) poster on the trial design for the ongoing ILLUMINATE-301 Phase 3 clinical trial of the combination of tilsotolimod and ipilimumab for unresectable or metastatic melanoma following failure of PD-1 inhibitor treatment. This poster will be on display on Sunday, October 21, 2018 from 12:45 – 1:45 PM CEST (6:45 – 8:45 AM EST) in Hall A3 at the Messe Munchen Congress Center in Munich, Germany.

Copies of these poster presentations are currently available on Idera’s corporate website at View Source

4th Quarter Clinical Efficacy and Safety Update
Based on the timing of disease assessment visits, the company plans an additional data cut later this quarter for the ILLUMINATE-204 trial to provide an update on clinical efficacy and safety data for up to 35 patients, including overall response rate (ORR) for all patients as well as for the Primary and Secondary Efficacy Patient Populations.

About Tilsotolimod (IMO-2125)
Tilsotolimod is a TLR 9 agonist that received Fast Track Designation from the US Food and Drug Administration (FDA) in 2017 for the treatment of anti-PD-1 refractory melanoma, in combination with ipilimumab as well as orphan drug designation from the FDA for the treatment of melanoma Stages IIb to IV. It signals the immune system to create and activate cancer-fighting cells (T-cells) to target solid tumors. Currently approved immuno-oncology treatments, specifically check-point inhibitors, work for some but not all, as many patients’ immune response is missing or weak and thus they do not benefit from the checkpoint therapy. Intratumoral injections with tilsotolimod are designed to selectively enable the T-cells to recognize and attack cancers that remained elusive and unrecognized by the immune system exposed to checkpoint inhibitors alone, while limiting toxicity or impact on healthy cells in the body.

About ILLUMINATE-204
The ILLUMINATE-204 study (2125-204) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda** (pembrolizumab) or Opdivo* (nivolumab) has failed. Melanoma is the most dangerous type of skin cancer. When it is metastatic, it means that the melanoma has spread to different parts of the body. ILLUMINATE-204 is a multi-center, two-arm Phase 1/2 study that tests the safety and effectiveness of tilsotolimod in combination with either ipilimumab (Yervoy) or pembrolizumab (Keytruda) for the treatment of patients with anti-PD-1 refractory metastatic melanoma.

For additional details about ILLUMINATE-204, please go to clinicaltrials.gov and search for study identifier NCT02644967.

About ILLUMINATE-301
The ILLUMINATE-301 study (2125-MEL-301) is for patients who have metastatic melanoma for whom treatment with an anti-PD-1 drug like Keytruda (pembrolizumab) or Opdivo (nivolumab) has failed. ILLUMINATE-301 is a global, multi-center, randomized Phase 3 study that compares the effectiveness and safety between two treatment groups: IMO-2125 combined with ipilimumab (Yervoy) versus ipilimumab given alone.

For additional details about ILLUMINATE-301, please go to clinicaltrials.gov and search for study identifier NCT03445533.

About Metastatic Melanoma
Melanoma is a type of skin cancer that begins in a type of skin cell called melanocytes. As is the case in many forms of cancer, melanoma becomes more difficult to treat once the disease has spread beyond the skin to other parts of the body such as the lymphatic system, liver or other visceral organs (metastatic disease). Because melanoma occurs in younger individuals, the years of life lost to melanoma are also disproportionately high when compared with other cancers. Although melanoma is a rare form of skin cancer, it comprises over 75% of skin cancer deaths. The American Cancer Society estimates that there were approximately 76,000 new invasive melanoma cases and 10,000 deaths from the disease in the USA in 2016. Additionally, according to the World Health Organization, about 132,000 new cases of melanoma are diagnosed around the world every year.

On October 19, 2018 QED Therapeutics reported the presentation of positive, reported that updated interim data of infigratinib (BGJ398), an orally administered, selective fibroblast growth factor receptor (FGFR) 1-3 tyrosine kinase inhibitor, for the treatment of advanced or metastatic cholangiocarcinoma (bile duct cancer) during a late-breaking poster discussion at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) (Press release, QED Therapeutics, OCT 19, 2018, View Source [SID1234576273]).

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In the open-label trial, which enrolled 71 patients with FGFR2 fusions/translocations, the confirmed overall response rate (cORR) was 26.9% (95% CI 16.8-39.1%) for all patients with the potential for confirmation (n=67) and an additional 56.7% experienced stable disease as their best response, resulting in a disease control rate of 83.6%. For patients who had received one or fewer prior treatment regimens, the cORR was 39.3% (n=28), whereas patients who had received two or more treatment regimens had a cORR of 17.9%. Median progression free survival was 6.8 months (95% CI 95% CI 5.3-7.6) and median overall survival was 12.5 months (95% CI 9.9-16.6 months).

"These updated data provide the most extensive experience for an FGFR inhibitor in advanced cholangiocarcinoma," said Milind Javle, M.D., professor, gastrointestinal medical oncology, The University of Texas MD Anderson Cancer Center and investigator on the Phase 2 infigratinib (BGJ398) study. "The high disease control rate and impressive overall survival are promising in a disease with no currently approved targeted treatments."

"These results show that infigratinib has strong potential to make a real difference in the lives of people with cholangiocarcinoma," said Susan Moran, M.D., M.S.C.E., chief medical officer of QED Therapeutics. "Importantly, we have initiated a pivotal, Phase 3 study in first-line cholangiocarcinoma in the hopes of offering patients an upfront chemotherapy-free treatment option."

The study also demonstrated that infigratinib-associated toxicity is manageable. Most common treatment-emergent adverse events (TEAE) were hyperphosphatemia (73.2%), fatigue (49.3%), stomatitis (45.1%), alopecia (38.0%) and constipation (35.2%). Grade 3/4 TEAEs occurred in 47 patients (66.2%), including hypophosphatemia (14.1%), hyperphosphatemia (12.7%) and hyponatremia (11.3%).

Cholangiocarcinoma affects approximately 8,000 to 10,000 patients a year in the United States. Currently, treatment options are limited, and survival rates are generally poor.

FGFR alterations have been implicated as an oncogenic driver across multiple solid tumors and hematological cancers – including roughly one out of every five cases of cholangiocarcinoma and urothelial carcinoma. Activating mutations in FGFRs are also found in multiple forms of pediatric skeletal dysplasias, including achondroplasia, which affects up to one out of every 15,000 live births.

A Phase 3 study comparing infigratinib to standard of care chemotherapy for first line cholangiocarcinoma has been initiated by QED Therapeutics