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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.

FUJIFILM ANNOUNCES ENTRY INTO U.S. COMPUTED TOMOGRAPHY MARKET WITH UNVEILING OF FCT EMBRACE AT ASTRO 2018

On October 21, 2018 FUJIFILM Medical Systems U.S.A., Inc., a leading provider of diagnostic imaging and medical informatics solutions, today introduced the FCT Embrace (Press release, Fujifilm, OCT 21, 2018, View Source [SID1234530089]). Powered by Analogic, the FCT Embrace is the world’s first 85cm wide bore computed tomography (CT) imaging unit with 64 or 128 slice configurations. Optimized for both oncology and radiology applications, the FCT Embrace, combined with other market-leading oncology solutions, offers enhanced and efficient CT Simulation with radiotherapy treatment planning capabilities. The unveiling at booth #3063 during the 2018 American Society for Radiation Oncology (ASTRO) Annual Meeting marks Fujifilm’s entry into the CT market, expanding its end-to-end diagnostic imaging product portfolio which is recognized for exceptional imaging at low dose.

"Fujifilm is a company of ‘firsts’ in diagnostic imaging. In 1936, we took our first steps in the development of X-ray film; and in 1983, we pioneered the first digitized radiography system in the world," said Johann Fernando, Ph.D., Chief Operating Officer of FUJIFILM Medical Systems U.S.A., Inc. "Once again we are innovating with the launch of the FCT Embrace, a solution that provides the most slices ever seen on an 85cm bore system. Designed to improve radiation oncology care, this advanced solution boosts patient comfort and security by offering the widest tabletop currently available at 49cm, and accommodating bariatric patients of up to 660lbs."

The new, state-of-the-art FCT Embrace provides exceptional imaging capabilities on an easy-to-use, standardized platform for both radiology and oncology. Designed to improve accuracy throughout the entire oncology care cycle, the 85cm bore optimally matches the rotational arc of the linear accelerator—offering easy and precise positioning options for simulation and treatment planning. This unique solution allows oncology patients to be imaged in their optimal treatment position at the full clinical image quality afforded by 64 slice or greater systems for the first time; maintaining the accuracy requirements radiation oncology demands without compromising diagnostic image quality.

With over 80 years of medical imaging experience, Fujifilm’s expertise in brilliant image quality, low dose, and patient comfort is now available to the CT market for oncology, interventional CT and radiology.

For more information on Fujifilm’s solutions, please visit: www.fujimed.com.

Genmab Announces Positive Topline Results in Phase III CASSIOPEIA Study of Daratumumab in Front Line Multiple Myeloma

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

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

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

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

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

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

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

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

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

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

Leap Therapeutics Presents Esophagogastric Cancer Data at ESMO 2018 Annual Congress

On October 21, 2018 Leap Therapeutics, Inc. (NASDAQ: LPTX) reported its clinical data from its ongoing Phase I/II study of DKN-01 in combination with Keytruda (pembrolizumab) in patients with advanced esophagogastric cancer at the European Society for Molecular Oncology (ESMO) (Free ESMO Whitepaper) 2018 Annual Congress (Press release, Leap Therapeutics, OCT 21, 2018, View Source [SID1234530017]).

Leap will host a live conference call and webcast on Monday, October 22 at 8:00 AM US Eastern Time / 2:00 PM Central European Time, with Samuel Klempner, MD, Director, Precision Medicine Program, The Angeles Clinic and Research Institute, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center. Dr. Klempner will describe his experience with patients in the study.

Clinical Data Presented at ESMO (Free ESMO Whitepaper)

Midway through the study, the combination of DKN-01 and pembrolizumab has demonstrated promising clinical activity with a 23.5% overall response rate and 58.8% disease control rate in evaluable gastric or gastroesophageal junction cancer patients who have been heavily pretreated and have not had prior anti-PD-1/PD-L1 therapy (PD-1/PD-L1 naïve). The combination has generated durable responses in subgroups less likely to respond to pembrolizumab monotherapy, for example, patients whose tumors are microsatellite stable (MSS) and/or PD-L1 negative. The combination of DKN-01 and pembrolizumab may have additive clinical benefit through the targeting of both innate and adaptive immunity. Data to date suggest that elevated tumor expression of DKK1 may correlate with better patient outcomes. Biomarker analyses are underway to guide future clinical development in gastroesophageal malignancies.

Esophagogastric Cancer Clinical Trial (P102)

The esophagogastric cancer clinical trial (P102) is a multipart study of DKN-01 as a monotherapy and in combination with paclitaxel or pembrolizumab. The arm evaluating DKN- 01 plus pembrolizumab includes both dose escalation and dose confirmation cohorts and is designed to assess the safety, pharmacokinetics and efficacy of the combination. Data from the monotherapy and paclitaxel arms of the study have been presented previously and will be updated later in the year.

As of the September 26, 2018 cut-off date for the presentation, forty-five patients have been enrolled in the DKN-01 plus pembrolizumab study, thirty-eight PD-1/PD-L1 naïve and seven refractory to PD-1/PD-L1 therapy. Two of the patients were enrolled in the 150mg DKN-01 dose, and forty-three patients at the 300mg DKN-01 dose. Leap expects that the PD-1/PD-L1 naïve group will complete enrollment before the end of 2018.

DKN-01 plus Keytruda
Clinical Results as of September 26, 2018

300mg DKN-01
Anti-PD1/PD-L1 Naïve

Patients

Response Rate

Disease
Control
Rate

Partial Response

Stable Disease

Progressive Disease

All responding patients in the study had MSS tumors. The overall response rate for Keytruda monotherapy in gastric or gastroesophageal junction patients with non-microsatellite instability high tumors in the KN-059 (n = 167) and KN-061 (n = 281) studies was 9.0% and 9.3%, respectively.

When this study is complete, Leap expects to choose an indication for a larger, controlled clinical study.

DKN-01 Clinical Perspectives Conference Call and Webcast:

On Monday, October 22, 2018 at 8:00AM ET/2:00PM CET, Leap will be hosting a conference call and webcast for the investment community. To access the conference call, please dial (866) 589-0108 (US/Canada Toll-Free) or (409) 231-2048 (international) and refer to conference ID 1249999. The presentation will also be webcast live and will be available under "Events & Presentations" in the Investor section of Leap’s website, View Source A replay of the webcast will be available on Leap’s website approximately two hours after the event and will be available for a limited time.

Daiichi Sankyo Presents Updated Results of [Fam-] Trastuzumab Deruxtecan (DS-8201) in Patients with HER2 Expressing Advanced Colorectal Cancer at 2018 European Society for Medical Oncology (ESMO) Congress

On October 21, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that updated phase 1 safety and efficacy data for [fam-] trastuzumab deruxtecan, an investigational HER2 targeting antibody drug conjugate (ADC), were presented for a subgroup of patients with heavily pretreated HER2 expressing colorectal cancer at the 2018 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Munich, Germany (Press release, Daiichi Sankyo, OCT 21, 2018, https://www.prnewswire.com/news-releases/daiichi-sankyo-presents-updated-results-of-fam–trastuzumab-deruxtecan-ds-8201-in-patients-with-her2-expressing-advanced-colorectal-cancer-at-2018-european-society-for-medical-oncology-esmo-congress-300734400.html [SID1234530016]).

An updated subgroup analysis in 19 evaluable patients with heavily pretreated HER2 expressing (defined as IHC ≥1+ or amplified) colorectal cancer receiving a recommended expansion dose of 6.4 mg/kg showed that [fam-] trastuzumab deruxtecan demonstrated a confirmed overall response rate of 15.8 percent (3 of 19 patients) and a disease control rate of 84.2 percent (16 of 19 patients). Median duration of response has not been reached and median progression-free survival was 3.9 months (95 percent CI: 2.1, 8.3) for this subgroup of patients. These patients had tumors with varying degrees of HER2 expression based on central IHC assessment of archival tissue, including six patients with HER2 IHC of zero (0). Tumor shrinkage primarily was observed in tumors with higher levels of HER2 IHC.

"We are encouraged by these preliminary results with [fam-] trastuzumab deruxtecan, particularly given the unmet medical need for patients with HER2 expressing colorectal cancer that has progressed on one or more prior therapies," said Takayuki Yoshino, MD, PhD, Director of Gastroenterology and Gastrointestinal Oncology at National Cancer Center Hospital East, Kashiwa, Japan, a study investigator. "These initial findings support further evaluation of [fam-] trastuzumab deruxtecan in this specific type of colorectal cancer."

"There are no therapies specifically approved for patients with HER2 expressing colorectal cancer, and continued study of [fam-] trastuzumab deruxtecan will provide a better understanding of the potential role of a HER2 targeting antibody drug conjugate in these patients," said Gilles Gallant, BPharm, PhD, Vice President, DS-8201 Global Team Leader, Oncology Research and Development, Daiichi Sankyo. "Patient enrollment is underway into our global phase 2 study evaluating safety and efficacy of [fam-] trastuzumab deruxtecan in patients with HER2 expressing advanced colorectal cancer."

Updated overall safety data as of August 10, 2018 across all subgroups of the ongoing phase 1 study with [fam-] trastuzumab deruxtecan in various HER2 expressing cancers were also reported at ESMO (Free ESMO Whitepaper). Among 259 patients who received at least one dose of [fam-] trastuzumab deruxtecan 5.4 or 6.4 mg/kg in Part 1 or Part 2 of the study (regardless of tumor type), the most common adverse events (≥30 percent, any Grade) included nausea (74.1 percent), decreased appetite (56.8 percent;) vomiting (43.6 percent), anemia (37.8 percent), alopecia (37.5 percent), fatigue (34.0 percent), diarrhea (33.6 percent) and constipation (32.8 percent). A total of 54.1 percent of patients experienced a ≥ Grade 3 adverse event and 22.8 percent had a serious adverse event, including 4.6 percent of patients who experienced an adverse event that led to death. As previously presented, five cases of Grade 5 interstitial lung disease (ILD)/pneumonitis were reported by the investigators for the overall population of the phase 1 study, none of which was observed in patients with colorectal cancer. Any reported cases of ILD/pneumonitis in the [fam-] trastuzumab deruxtecan clinical development program are evaluated by an independent adjudication committee.

Unmet Need in Colorectal Cancer
Colorectal cancer is the third most common cancer worldwide. In 2012, there were approximately 1.36 million new cases diagnosed and 690,000 deaths worldwide.1 Approximately 25 percent of patients have metastatic disease at diagnosis, meaning the disease has spread to distant organs, and about 50 percent of patients with colorectal cancer will eventually develop metastases.2 Prognosis for these patients remains poor.3

An increase in the number of approved targeted therapies for advanced colorectal cancer over the past decade has helped improve outcomes for some patients, however efficacy and tolerability of second and third-line treatments remain limited.4,5,6,7,8 Approximately 3 percent of colorectal cancers overexpress the HER2 protein, which is a well-established therapeutic target in breast and gastric cancer.4 In addition, research indicates that HER2 amplification may be associated with resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy and shorter survival.9,10 Currently, no approved HER2 targeting therapies exist for patients with colorectal cancer.

About the [Fam-] Trastuzumab Deruxtecan Phase 1 Study
An open-label, two-part phase 1 study is currently evaluating [fam-] trastuzumab deruxtecan in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerant to standard treatment, or for whom no standard treatment is available. The primary objective of the dose escalation phase of this study was to assess the safety and tolerability of [fam-] trastuzumab deruxtecan and determine the maximum tolerated dose. Data from this part of the study were published in the Lancet Oncology.11

In the dose expansion part of the phase 1 study, [fam-] trastuzumab deruxtecan is given in one of two doses (5.4 mg/kg and 6.4 mg/kg) to patients with HER2 positive advanced or metastatic breast cancer and gastric cancer, HER2 low expressing breast cancer and other HER2 expressing solid tumors including colorectal cancer. Overall, 292 patients have been enrolled into this phase 1 study of [fam-] trastuzumab deruxtecan. For more information about the study, visit ClinicalTrials.gov.

About [Fam-] Trastuzumab Deruxtecan
[Fam-] trastuzumab deruxtecan (DS-8201; [fam-] trastuzumab deruxtecan in U.S. only; trastuzumab deruxtecan in other regions of world) is the lead product in the investigational ADC Franchise of the Daiichi Sankyo Cancer Enterprise. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary ADC technology, [fam-] trastuzumab deruxtecan is comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker. It is designed to target and deliver chemotherapy inside cancer cells and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

A broad and comprehensive development program with [fam-] trastuzumab deruxtecan is underway in North America, Europe and Asia. [Fam-] trastuzumab deruxtecan is in phase 3 development versus ado-trastuzumab emtansine (T-DM1) (DESTINY-Breast03) and versus investigator’s choice post T-DM1 (DESTINY-Breast02) for HER2 positive metastatic breast cancer; pivotal phase 2 clinical development for HER2 positive metastatic breast cancer resistant or refractory to T-DM1 (DESTINY-Breast01); pivotal phase 2 development for HER2 positive advanced gastric cancer resistant or refractory to trastuzumab (DESTINY-Gastric01); phase 2 development for HER2 expressing advanced colorectal cancer; phase 2 development for metastatic non-squamous HER2 overexpressing or HER2 mutated NSCLC; and, phase 1 development in combination with nivolumab for HER2 expressing metastatic breast and bladder cancer.

[Fam-] trastuzumab deruxtecan has been granted Breakthrough Therapy designation for the treatment of patients with HER2 positive, locally advanced or metastatic breast cancer who have been treated with trastuzumab and pertuzumab and have disease progression after T-DM1, and Fast Track designation for the treatment of HER2 positive unresectable and/or metastatic breast cancer in patients who have progressed after prior treatment with HER2 targeted therapies including T-DM1 by the U.S. Food and Drug Administration (FDA). [Fam-] trastuzumab deruxtecan has received SAKIGAKE Designation for the treatment of HER2 positive advanced gastric or gastroesophageal junction cancer by the Japan Ministry of Health, Labour and Welfare (MHLW).

[Fam-] trastuzumab deruxtecan is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.