On January 15, 2021 Five Prime Therapeutics, Inc. (NASDAQ: FPRX) reported clinical results from the global, randomized, double-blind placebo-controlled Phase 2 FIGHT trial evaluating first-in-class targeted therapy bemarituzumab in advanced gastric or gastroesophageal junction (GEJ) cancer (Press release, Five Prime Therapeutics, JAN 15, 2021, View Source [SID1234574049]). Trial results were presented in a late-breaking oral presentation today by UCLA Health’s Zev Wainberg, M.D., at the 2021 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Virtual Annual Symposium (ASCO GI). The ASCO (Free ASCO Whitepaper) GI presentation slides are available on the company’s website.

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The FIGHT trial evaluated bemarituzumab plus chemotherapy (mFOLFOX6) versus placebo plus chemotherapy in patients with fibroblast growth factor receptor 2b-positive (FGFR2b+), non HER2 positive frontline advanced gastric or GEJ cancer. The trial enrolled 155 patients in 15 countries across Asia, the European Union, and the United States, with 77 patients randomized to the bemarituzumab arm and 78 patients to the placebo arm.

The Phase 2 trial met all three efficacy endpoints and demonstrated statistically significant and clinically meaningful improvements in the primary endpoint of progression-free survival (PFS) and secondary endpoints of overall survival (OS) and overall response rate (ORR). Additional analysis showed a correlation between benefit and the percentage of FGFR2b+ tumor cells, confirming both the importance of the FGFR2b target and the activity of bemarituzumab against this target.

"Systemic chemotherapy is the standard of care for this deadly and aggressive form of gastric cancer. We are strongly encouraged by these data and the potential for a frontline targeted treatment that can improve overall survival," said Zev A. Wainberg, M.D., Associate Professor of Medicine at UCLA, Co-director of the Gastrointestinal Oncology Program and Director of Early Phase Clinical Research at the Jonsson Comprehensive Cancer Center. "The FIGHT trial results demonstrate that treatment with bemarituzumab in combination with chemotherapy can deliver a significant reduction in the risk of disease progression and death in gastric cancer patients whose tumors overexpress FGFR2b."

"The Phase 2 FIGHT clinical trial results validate our pioneering work on the role of FGFR2b overexpression in gastric cancer, and we’re excited about the implications of this new scientific understanding for other cancers," said Helen Collins, M.D., Five Prime’s Executive Vice President and Chief Medical Officer. "With these data in hand, we plan to continue to collaborate with regulatory agencies on next steps, initiate a global Phase 3 trial in gastric cancer and begin studying bemarituzumab in other epithelial cancers that overexpress FGFR2b."

The incidence of all grade adverse events was similar in the bemarituzumab and placebo arms of the study (100% vs 98.7%, respectively). Corneal events were reported more frequently in the bemarituzumab arm (67.1% vs 10.4%), with the most common corneal events in the bemarituzumab arm being dry eye (26.3%), keratitis (15.8%) and punctate keratitis (14.5%). Stomatitis (31.6% vs 13.0%) and elevated transaminases (34.2% vs 19.5%) were also more common in the bemarituzumab arm. Grade 3 and higher adverse events (82.9% vs 74.0%), serious adverse events (31.6% vs 36.4%) and deaths (6.6% vs 5.2%) were comparable across arms.

Ocular events are common in therapies targeting FGFR and were also reported in the FIGHT trial. More patients in the FIGHT trial discontinued bemarituzumab compared to placebo due to an adverse event (34.2% vs 5.2%), the majority (21 of 26 patients) due to an ocular event.

The discontinuation of bemarituzumab due to an ocular event decreased the median duration of exposure to bemarituzumab by 3.2 weeks; from 25.3 weeks (n=55, range: 2.0 to 71.7 weeks) to 22.1 weeks (n=21, range: 12.0 to 46.7 weeks).

In designing the Phase 3 trial, the company plans to incorporate findings from the FIGHT trial including baseline eye exams, prophylactic lubricating eye drops and close monitoring for signs and symptoms of corneal toxicity, including dry eye.

Five Prime Webcast /Conference Call Information

Five Prime Therapeutics will host a KOL conference call and live audio webcast following ASCO (Free ASCO Whitepaper) GI on Friday, January 15, 2021 at 4:30pm (EST) / 1:30pm (PST) to review the Phase 2 FIGHT clinical trial results and provide an update on the bemarituzumab program. The presentation will feature members of the Five Prime management team and Zev A. Wainberg, M.D., Associate Professor of Medicine at UCLA, Co-director of the Gastrointestinal Oncology Program and Director of Early Phase Clinical Research at the Jonsson Comprehensive Cancer Center, and an investigator in the trial.

To participate in the conference call, please dial (877) 878-2269 (domestic) or (253) 237-1188 (international) and refer to conference ID: 2063209. To access the live webcast please visit View Source

An archived copy of the webcast will be available on Five Prime’s website beginning approximately two hours after the conference call. Five Prime will maintain an archived replay of the webcast on its website for at least 30 days after the conference call.

About FGFR2b

The fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) pathway is implicated in the development and growth of cancer cells. FGFR2b is a splice form of FGFR which can be found in tumors of epithelial origin. Data from the FIGHT trial suggests that approximately 30 percent of patients with non HER2 positive gastroesophageal cancers overexpress FGFR2b.1 Five Prime and Roche Tissue Diagnostics have also found that FGFR2b is overexpressed in numerous other cancers, including squamous non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), ovarian, pancreatic and intrahepatic cholangiocarcinoma.

About Bemarituzumab

Bemarituzumab (anti-FGFR2b) is a first-in-class targeted antibody that blocks fibroblast growth factors (FGFs) from binding and activating FGFR2b, inhibiting several downstream pro-tumor signaling pathways and potentially slowing cancer progression. Bemarituzumab is being developed in gastric and GEJ cancer as a targeted therapy for tumors that overexpress FGFR2b. The company is also evaluating the potential for bemarituzumab in other cancers that overexpress FGFR2b.

Five Prime granted an exclusive license to Zai Lab to develop and commercialize bemarituzumab in Greater China, and Zai Lab collaborated with Five Prime on the Phase 2 FIGHT trial in Greater China.

About Gastric Cancer and GEJ Cancer

Gastric cancer, also known as stomach cancer, is the third most common cause of cancer death worldwide and, excluding non-melanoma skin cancer, the fifth most common cancer worldwide, with over 1,000,000 new cases diagnosed each year.2 For HER2 negative patients, frontline therapy available today is the same systemic chemotherapy available since the 1990s.3,4

On January 15, 2021 NuCana plc (NASDAQ: NCNA) reported interim data from the ongoing NuTide:302 study at the ASCO (Free ASCO Whitepaper) GI Conference, being held virtually January 15-17, 2021 (Press release, Nucana BioPharmaceuticals, JAN 15, 2021, View Source [SID1234574048]).

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NuTide:302 is a three-part study investigating NUC-3373, NuCana’s targeted thymidylate synthase inhibitor, in heavily pre-treated patients with metastatic colorectal cancer. The study is evaluating NUC-3373’s optimal dose and schedule in combination with agents commonly used to treat patients with colorectal cancer and is assessing safety, pharmacokinetics and anti-cancer activity. NUC-3373 has been designed to overcome the main challenges associated with 5-FU and capecitabine, including cancer-resistance mechanisms which limit efficacy, off-target toxicity and administration burdens.

The ASCO (Free ASCO Whitepaper) GI presentation highlighted data from 37 patients treated in Part I of the study who received NUC-3373 either as monotherapy or in combination with leucovorin. Ten patient case studies highlighted NUC-3373’s ability to stabilize disease and achieve prolonged durations of progression-free survival. Many patients achieved longer progression-free survival on NUC-3373 than they had on their prior line of therapy and five patients experienced tumor shrinkage. These patients included:

A fourth-line patient who achieved a Partial Response with a 40% reduction in tumor volume;

A third-line patient who achieved a 28% reduction in tumor volume after their disease rapidly progressed through all prior fluoropyrimidine-containing regimens.

Among the efficacy-evaluable population, a disease control rate of 62% was achieved.

In addition to these encouraging efficacy signals, the presentation compared the safety profile of NUC-3373 in Part I of the study with historical data for 5-FU and capecitabine in the front-line treatment of patients with colorectal cancer. NUC-3373 was well tolerated with no hand-foot-syndrome or neutropenia as well as lower rates of diarrhea, mucositis and stomatitis.

Dr. Andrew Coveler, Associate Professor at the University of Washington School of Medicine and Fred Hutchinson Cancer Research Center and an investigator in the NuTide:302 study, remarked: "I am encouraged by both the clinical activity and safety of NUC-3373. To observe this anti-cancer activity, including a Partial Response, in such a heavily pre-treated patient population is very promising. In addition, NUC-3373 has been well tolerated and its safety appears favorable when compared to 5-FU and capecitabine. As such, I look forward to advancing NUC-3373’s development in patients with colorectal cancer."

"We are very pleased with these additional data from Part I of the NuTide:302 study," said Hugh S. Griffith, NuCana’s Founder and CEO. "It was particularly encouraging to observe tumor shrinkages, prolonged disease stabilization and a favorable safety profile in a patient population that had received at least two prior fluoropyrimidine-containing regimens. We look forward to continuing Part II of the study in which NUC-3373 is being combined with leucovorin and either oxaliplatin or irinotecan. Our objective is to replace 5-FU and capecitabine with NUC-3373 as the backbone of treatment for patients with colorectal cancer."

Details of the poster presentation are as follows:

Title: A phase Ib study of NUC-3373 in combination with standard therapies in

advanced/metastatic colorectal cancer (NuTide:302)

Session: Colorectal Cancer

Abstract Number: 93

On January 15, 2021 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that it will participate in a Fireside Chat with Andrew D’Silva of B. Riley Securities on Wednesday, January 20, 2021 at 10:30 am ET (Press release, Infinity Pharmaceuticals, JAN 15, 2021, View Source [SID1234574047]).

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B. Riley is limiting the live audience to institutional investors, investor relations, and employees of each presenting company. Private investors will not be given access to the live conference, but a replay will be available on the Events and Presentations page of the Infinity Pharmaceuticals website following the conference.

On January 15, 2021 Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, reported new and updated clinical data for the HER2‑targeted bispecific antibody zanidatamab, in both HER2-expressing biliary tract cancer (BTC) and gastroesophageal adenocarcinoma (GEA) (Press release, Zymeworks, JAN 15, 2021, View Source [SID1234574037]). The data are being presented today at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, taking place virtually January 15 – 17, 2021.

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"Data presented today at ASCO (Free ASCO Whitepaper) GI continue to demonstrate the potential of zanidatamab in advanced HER2-expressing cancers with high unmet need. The response rates and median duration of response in refractory BTC and GEA compare favorably to current standard of care and emerging treatments," said Diana Hausman, M.D., Chief Medical Officer at Zymeworks. "The BTC data were the basis of the recent Breakthrough Therapy designation granted by the FDA, a key step in helping zanidatamab become the first potential HER2‑targeted therapy approved in this indication. Furthermore, the activity in GEA supports our goal of establishing zanidatamab as the foundational HER2-targeted therapy for GEA and other HER2-positive cancers, not only in later stage disease, but also in earlier lines of treatment."

The following presentations are available to conference registrants on the ASCO (Free ASCO Whitepaper) conference website as well as to the general public at ir.zymeworks.com/events-and-presentations/.

Zanidatamab Monotherapy and Chemotherapy Combinations in HER2-Expressing Gastroesophageal Cancer – Clinical Results – Abstract #164

Zanidatamab (ZW25) in HER2-expressing gastroesophageal adenocarcinoma (GEA): Results from a Phase 1 study (Presenter: Funda Meric-Bernstam, MD, UT MD Anderson Cancer Center, TX; Rapid Abstract oral presentation on Friday, January 15, 11:30 am-12:15 pm ET)

HER2 is overexpressed in approximately 20% of GEA patients. For these patients, trastuzumab in combination with chemotherapy is the only approved HER2‑targeted therapy. Treatment options are currently limited if disease progression occurs after trastuzumab in combination with chemotherapy.

Findings from an ongoing Phase 1 study of zanidatamab in HER2-positive GEA were last presented in July 2020. New and updated results are being presented in a Rapid Abstract oral presentation today, January 15th, at 11:30 am ET at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium followed by a webcast at 5:00 pm ET to discuss the data, led by zanidatamab study investigator Dr. Funda Meric-Bernstam, MD.

The data being reported are from HER2-expressing GEA patients who received zanidatamab either as monotherapy (n=35) or in combination with chemotherapies (n=28). The groups had a median of two to three (range 0-7) prior therapies, with a high percentage (88-91%) having received prior HER2-targeted therapies. The data continue to demonstrate that zanidatamab is well tolerated with the majority of treatment-related AEs considered mild to moderate in severity (Grade 1 or 2) and manageable in the outpatient setting.

In 33 response-evaluable patients who received zanidatamab as monotherapy (10 mg/kg weekly or 20 mg/kg every two weeks), the objective response rate (ORR) was 39% (13/33), 11 (33%) of which were confirmed by a subsequent scan. The disease control rate (DCR) was 61% (20/33) and median duration of response (DOR) was six months.

In 10 response-evaluable patients who received zanidatamab (20 mg/kg every two weeks) plus paclitaxel, the ORR was 60% (6/10), five (50%) of which were confirmed by a subsequent scan including one patient who experienced a complete response. The DCR was 90% (9/10) for this group. In 14 response-evaluable patients who received zanidatamab (20 mg/kg every two weeks or 30 mg/kg every three weeks) plus capecitabine, the confirmed ORR was 57% (8/14) and the DCR was 71% (10/14). Overall the median DOR for zanidatamab plus chemotherapy was 8.9 months and the median progression-free survival (PFS) was 5.6 months with eight (29%) patients still on study at the time of data cut-off.

In 2019, Zymeworks initiated a global, multicenter Phase 2 clinical trial (NCT03929666) evaluating zanidatamab in combination with standard of care chemotherapy for the first-line treatment of HER2-positive metastatic GEA. Taken together, data from the Phase 1 and Phase 2 studies further support the company’s plans to initiate, with partner BeiGene, a pivotal study for zanidatamab plus chemotherapy +/- tislelizumab (anti-PD1), as first-line treatment for advanced HER2-positive GEA in mid-2021.

Zanidatamab Monotherapy in HER2-Amplified Biliary Tract Cancer – Clinical Results – Abstract #299

Zanidatamab (ZW25) in HER2-positive biliary tract cancers (BTCs): Results from a Phase 1 study (Presenter: Funda Meric-Bernstam, MD, UT MD Anderson Cancer Center, TX)

Globally, more than 210,000 people are diagnosed with BTC every year and as many as one-fifth of these patients have tumors that express HER2. Currently no HER2‑targeted therapy has been approved for the treatment of BTC.

Findings from the ongoing Phase 1 study of zanidatamab in HER2-amplified BTC were last shared in July 2020. The updated and new results are being presented today in a poster session at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium.

Data were reported on 21 patients diagnosed with HER2-amplified BTC who received zanidatamab at the recommended dose of 20 mg/kg every two weeks. Patients received a median of two (range 1-8) prior therapies and five (24%) of the patients were previously treated with the HER2-targeted therapy trastuzumab.

Zanidatamab was well tolerated and demonstrated durable antitumor activity in these patients. All zanidatamab-related adverse events (AEs) were mild or moderate in severity (Grade 1 or 2). The confirmed objective response rate (ORR) in trastuzumab-naïve patients was 47% (7/15) and overall ORR was 40% (8/20). The overall disease control rate (DCR) was 65% (13/20), and median duration of response (DOR) was 7.4 months with several patients still on study at the time of data cut-off.

Based on these results, in July 2020 Zymeworks initiated a global pivotal Phase 2b trial (HERIZON-BTC-01; ZW25-203) [NCT04466891] of zanidatamab monotherapy in patients with HER2-amplified BTC that has been previously treated with at least one gemcitabine-containing systemic chemotherapy regimen. The US Food and Drug Administration (FDA) recently granted Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified BTC, based on evaluation of the Phase 1 data. This global pivotal Phase 2 study of zanidatamab in BTC may enable the submission of a Biologics License Application by Zymeworks in the United States as early as 2022.

Zanidatamab HERIZON-BTC-01 Trial in Progress Poster Presented Today – Abstract TPS352

A Phase 2b, Open-label, Single-arm Study of Zanidatamab (ZW25) Monotherapy in Patients with Advanced or Metastatic HER2-amplified Biliary Tract Cancers (BTC): HERIZON-BTC-01 Study (Lead Author: Shubham Pant, MD, UT MD Anderson Cancer Center, TX)

Zymeworks is presenting a trial in progress poster at ASCO (Free ASCO Whitepaper) GI for a global pivotal Phase 2 trial in HER2-amplified BTC (HERIZON-BTC-01; ZW25-03). Multiple clinical sites are now open to enrollment in the U.S., South Korea, Italy and Spain, with additional sites planned in Canada, Chile, China, France and the UK [Phase 2:NCT04466891]. This study is designed to support accelerated approval based on a primary endpoint of objective response rate, and key secondary endpoints of duration of response and safety.

About the Zanidatamab Phase 1 Clinical Trial

Zymeworks’ Phase 1 zanidatamab study has three parts. From part one of the study (the dose-escalation phase), the recommended single-agent dose was determined to be 20 mg/kg once every two weeks or 10 mg/kg weekly. In the second part of the study (the cohort expansion phase), additional patients are being enrolled to further assess zanidatamab’s single-agent tolerability and antitumor activity against a variety of cancer types in different settings. The third part of the study (the combination phase) is underway and evaluating zanidatamab in combination with selected chemotherapy agents in gastroesophageal and breast cancer patients with HER2 high or lower HER2 expression levels.

About Zanidatamab

Zanidatamab is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding, and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2, and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2. The FDA has granted Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified BTC, and two Fast Track designations to zanidatamab, one as a single agent for refractory BTC and one in combination with standard of care chemotherapy, for first-line gastroesophageal adenocarcinoma (GEA). These designations mean zanidatamab is eligible for Accelerated Approval, Priority Review and Rolling Review, as well as intensive FDA guidance on an efficient drug development program. Zanidatamab has also received Orphan Drug designations for the treatment of biliary tract, gastric and ovarian cancers, as well as Orphan Drug designation for the treatment of gastric cancer from the European Medicines Agency.

On January 15, 2021 Isofol Medical AB (publ) ("Isofol"), (Nasdaq First North Premier Growth Market: ISOFOL) reported that a poster presentation is presented at ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI) (Press release, Isofol Medical, JAN 15, 2021, View Source [SID1234574046]). The abstract present results from the Phase I/IIa ISO-CC-005 study which shows a correlation between clinical benefit and gene expression of the folate pathway in patients with metastatic colorectal cancer treated with 5-FU-based chemotherapy in combination with arfolitixorin. Furthermore, Isofol gives an update of the timing of the interim analysis in the global Phase III AGENT study.

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In connection to ASCO (Free ASCO Whitepaper)-GI, Isofol together with QuartzBio, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, will present a poster with the title "Folate pathway gene expression in metastatic colorectal cancer patients treated with arfolitixorin/5-FU-based chemotherapy" on asco.org between 2.00 PM – 12.15 AM CET on January 15 (registration required). The poster is available at the same time on the website.

The poster present results from the ISO-CC-005 study where it was found that the gene expression levels of TYMS are significantly associated with clinical benefit (partial response or stable disease), in patients treated with 5-FU-based chemotherapy in combination with arfolitixorin.

Given the role of TYMS in the folate metabolic pathways, Isofol plan to further assess its predictive potential on a larger cohort which will provide additional cues on the use of this and other related genes as predictive markers for treatment outcome and their role in the mode of action of arfolitixorin, as part of the ongoing Phase III AGENT study.

The AGENT study was fully recruited in December 2020 with 440 patients and the company is currently awaiting the interim analysis, which was initiated when the 330th patients had been treated for 16 weeks and had two tumor evaluations.

Lockdowns due to COVID-19 of participating hospitals have had impact on timelines for gathering data. Data has been provided to third parties and is currently being reviewed, quality controlled, and prepared. Once that has been done the iDSMB (independent Data and Safety Monitoring Board) will analyze safety and efficacy (ORR, Overall Respons Rate and PFS, Progression-Free Survival) and give a recommendation. Recruitment will either be stopped after 440 patients or expanded to 660 patients, to further strengthen the statistical power for PFS). Based on the current available information, Isofols estimation is that the recommendation from iDSMB, based on the interim analysis, is expected during Q1 2021.