On May 26, 2022 Inspirna, Inc., a clinical stage biopharmaceutical company developing first-in-class small molecule and biologic cancer therapeutics, reported new data from the ongoing Phase 1b clinical trial studying RGX-202-01 in combination with FOLFIRI and bevacizumab (FOLFIRI/BEV) in second-line advanced colorectal cancer (CRC) at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 3-7 in Chicago, Illinois (Press release, Inspirna, MAY 26, 2022, View Source [SID1234615133]).

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"These exciting new data show the potential of RGX-202-01 to drive meaningful responses in patients with advanced or metastatic colorectal cancer, especially in the KRAS mutant setting where there is a clear opportunity to improve on the standard of care," said Andrew Hendifar, M.D., Assistant Professor at Cedars-Sinai Medical Center and principal investigator on the study. "RGX-202-01 employs a novel mechanism by inhibiting SLC6a8, part of a pathway that becomes activated by colorectal cancer cells in order for these cells to survive, proliferate, and metastasize. Importantly, along with its preliminary signal of efficacy, these results also demonstrate that RGX-202-01 is very well-tolerated, enabling it to be combined with FOLFIRI/BEV and provide further optionality in this difficult-to-treat indication."

RGX-202-01 is an oral, potential first-in-class small molecule inhibitor of SLC6a8, a creatine transporter that drives colorectal cancer and certain other cancers’ progression. It is currently being evaluated in a Phase 1b dose escalation and expansion study in combination with FOLFIRI/BEV in second-line, advanced or metastatic CRC. The primary endpoint of the study is to determine maximum tolerated dose (MTD), overall response rate (ORR), and treatment-emergent adverse events (TEAEs). In the dose escalation stage of the study, two dose levels of RGX-202-01 with FOLFIRI/BEV have been evaluated in patients with advanced or metastatic CRC who have progressed on available oxaliplatin based first line therapy. In the ongoing expansion stage, additional patients with CRC are being treated at the dose of 3000mg PO BID to provide further characterization of the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the treatment.

Key findings to be presented at ASCO (Free ASCO Whitepaper) 2022:

The data cutoff for the presentation is April 28, 2022. As of data cutoff, 19 patients were enrolled in the study, including eight total patients in the dose escalation stage treated with either 2400mg twice daily (BID) of RGX-202-01 plus FOLFIRI/BEV (n = 4) or 3000mg BID RGX-202-01 plus FOLFIRI/BEV (n = 4), and 11 patients treated in the expansion stage with 3000mg BID RGX-202-01 plus FOLFIRI/BEV.
The dose escalation stage did not reach an MTD.
No dose limiting toxicities (DLT) were observed at either 2400mg BID or 3000mg BID doses.
There were only two Grade 4 TEAEs, and one of those was considered unrelated to treatment with RGX-202-01, and no Grade 5 TEAEs were observed.
17 patients were evaluable for response per RECIST v1.1 at data cutoff, of which 10 patients had KRAS mutant tumors and seven patients had KRAS wild-type tumors.
In the KRAS mutant population, five patients (50%) had confirmed partial responses (PR) and five patients (50%) had stable disease (SD).
In the KRAS wild-type population, one patient (14%) had an unconfirmed PR, five patients (71%) had SD, and one patient (14%) had progressive disease (PD).
Preliminary median progression-free survival (mPFS) was 11.8 months in the enrolled patients with KRAS mutant tumors.
Tumor regression was observed to deepen over time in patients with KRAS mutant tumors, with first radiographic achievement of PR appearing as late as 40 weeks post-treatment induction.
Overall, results show ORR and mPFS exceed expected benefit with standard-of-care alone in second-line CRC.
"We are very encouraged by the data reported today showing a strong signal of activity and meaningful responses, especially in patients harboring KRAS mutant tumors," said Masoud Tavazoie, M.D., Ph.D., Chief Executive Officer of Inspirna. "The results not only support our efforts to continue advancing RGX-202-01 in CRC, but also validate the ability of our RNA-DRIVEr platform to discover and develop new drug candidates with the potential to address cancers of high unmet medical need. We look forward to sharing these results at ASCO (Free ASCO Whitepaper) and further advancing RGX-202-01 drug development."

The abstract is available for viewing on the ASCO (Free ASCO Whitepaper) website, and the poster will be available at View Source following the session.

Poster Presentation Details

Title: Phase 1b study of RGX-202-01, a first-in-class oral inhibitor of the SLC6A8/CKB pathway, in combination with FOLFIRI and bevacizumab (BEV) in second-line advanced colorectal cancer (CRC)

Date and time: Saturday, June 4, 2022, 8:00 a.m. CDT

Session: Gastrointestinal Cancer—Colorectal and Anal

Abstract ID: 3579

On May 26, 2022 Laekna Therapeutics, a clinical-stage biotechnology company developing innovative medicines to treat cancer and liver diseases, reported that two first patients have been dosed in the U.S. and China, respectively, in a Phase Ib/III clinical trial that evaluates the efficacy and safety of afuresertib in combination with fulvestrant, an estrogen receptor antagonist, in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer who failed after 1-2 lines of CDK4/6 inhibitors, endocrine, or chemotherapy treatments (Press release, Laekna Therapeutics, MAY 26, 2022, View Source;breast-cancer-301555843.html [SID1234615149]).

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Afuresertib is an investigational AKT kinase inhibitor with global exclusive rights obtained from Novartis. The lead investigator of the study in China is Professor Binghe Xu, Academician of the Chinese Academy of Engineering and Director of the National Clinical Research Center for Cancer, while Professor Peter Kaufman, Lead Medical Oncologist from The University of Vermont Medical Center, is the lead investigator of the study in the U.S. Patient enrollment has begun simultaneously at the Piedmont Cancer Institute in the U.S. and Tianjin Medical University Cancer Institute & Hospital in China, and will soon begin in several other sites. Laekna will initiate a Phase III global pivotal trial after afuresertib plus fulvestrant shows a manageable safety profile in the Phase Ib study.

Breast cancer is the most common cancer among women worldwide. About 62% and 68% of all breast cancer patients in China and the U.S. are HR+/HER2- respectively[1,2]. "Although most patients with this type of breast cancer initially benefit from endocrine ±CDK4/6 inhibitors and/or chemotherapy as first- or second-line treatment, resistance occurs in most patients in about two years. I look forward to the results from the clinical study of afuresertib in combination with fulvestrant, which could offer a new treatment option for treatment-resistant breast cancer," said Professor Xu.

"Our team has been working closely with the investigators to overcome obstacles and dose the first patients both in the U.S. and China according to schedule, which demonstrated Laekna’s robust global clinical development capabilities," said Dr. Yong Yue, Chief Medical Officer of Laekna Therapeutics. "Our next step is to expedite simultaneous global development of afuresertib plus fulvestrant to bring hope to patients who have developed treatment resistance."

On May 26, 2022 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported the presentation of research across various types of cancer from its oncology portfolio during the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (#ASCO22), which is taking place virtually and in-person in Chicago from June 3 to 7 (Press release, Eisai, MAY 26, 2022, View Source [SID1234615166]). Notable presentations include a poster discussion of safety and efficacy data (NCT03386942(New Window); Abstract: #5513) from the platinum-resistant ovarian cancer cohort expansion of a Phase 1 study evaluating the antibody drug conjugate (ADC) co-developed by Eisai and Bristol Myers Squibb (Headquarters: the United States), farletuzumab ecteribulin (MORAb-202), as well as a poster presentation featuring dose optimization findings for farletuzumab ecteribulin (NCT03386942(New Window); Abstract: #3090).

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"Safety and efficacy analyses in platinum-resistant ovarian cancer for farletuzumab ecteribulin suggest antibody drug conjugates may represent a promising therapeutic strategy for these patients with limited treatment options," said Dr. Takashi Owa, President, Oncology Business Group at Eisai. "Eisai’s first antibody drug conjugate combines our in-house developed anti-folate receptor alpha antibody and our anticancer agent eribulin using an enzyme cleavable linker, illustrating our dedication to building on our medicines to improve cancer care for more patients."

New research from the LEAP (LEnvatinib And Pembrolizumab) clinical program evaluating lenvatinib (LENVIMA) plus pembrolizumab (KEYTRUDA), the anti-PD-1 therapy from Merck & Co., Inc., Rahway, NJ, USA, includes subgroup analyses from the pivotal Phase 3 CLEAR (Study 307)/KEYNOTE-581 trial evaluating the combination in patients with advanced renal cell carcinoma (RCC) and Phase 3 Study 309/KEYNOTE-775 trial evaluating the combination in patients with advanced endometrial carcinoma (EC). A poster discussion will evaluate the impact of subsequent therapies in patients with advanced RCC receiving the combination (NCT02811861(New Window); Abstract: #4514); while a poster presentation will discuss the efficacy of next line therapy after treatment with lenvatinib plus pembrolizumab in advanced EC (NCT03517449(New Window); Abstract: #5587).

"The combination of lenvatinib plus pembrolizumab has helped to expand physicians’ arsenal of treatment options for patients living with advanced renal cell carcinoma and advanced endometrial carcinoma around the world," said Richard C. Woodman, MD, Chief Clinical Officer, Oncology Business Group at Eisai. "Our data at ASCO (Free ASCO Whitepaper) 2022 demonstrate our commitment to continuing to investigate the combination through post-hoc analyses with the goal of providing healthcare professionals with tools to support them in making better-informed treatment decisions for their patients."

In March 2018, Eisai and Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside the United States and Canada), through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib, both as monotherapy and in combination with pembrolizumab. To date, more than 20 trials have been initiated under the LEAP clinical program, which is evaluating the combination across more than 10 different tumor types.

In June 2021, Eisai and Bristol Myers Squibb entered into an exclusive global strategic collaboration agreement for the co-development and co-commercialization of farletuzumab ecteribulin, a folate receptor alpha (FRα)-targeting ADC. Eisai and Bristol Myers Squibb are currently investigating farletuzumab ecteribulin in FRα-positive solid tumors (inclusive of endometrial, ovarian, lung and breast cancers) in two studies: a Phase 1 clinical study in Japan and a Phase 1/2 clinical study in the United States.

This release discusses investigational compounds and investigational uses for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational compounds or investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval.

The full list of Eisai presentations is included below. The majority of abstracts have been made available on Thursday, May 26, 2022, at 5:00 PM EDT and will be available on demand via ASCO (Free ASCO Whitepaper)’s website.

　

Cancer Type Study/Compound Abstract Title Abstract Type & Details
Pipeline
Gynecologic Cancer Farletuzumab Ecteribulin Safety and Efficacy of MORAb-202 in Patients (pts) With Platinum-Resistant Ovarian Cancer (PROC): Results From the Expansion Part of a Phase 1 Trial.
Poster Discussion
Abstract #5513
June 4, 2022
5:30 PM EDT

Shin Nishio, MD, PhD
Kurume University School of Medicine

Farletuzumab Ecteribulin Dose Optimization for MORAb-202, an Antibody-Drug Conjugate (ADC) Highly Selective for Folate Receptor-Alpha (FRα), Using Population Pharmacokinetic (PPK) and Exposure-Response (E-R) Efficacy and Safety Analyses.
Poster Presentation
Abstract #3090
June 5, 2022
9:00 AM EDT

Seiichi Hayato
Eisai
Lenvatinib Combinations

(Plus Pembrolizumab, Pembrolizumab and Chemotherapy or Pembrolizumab and Belzutifan)

Genitourinary Cancer CLEAR (Study 307)/ KEYNOTE-581 Impact of subsequent therapies in patients (pts) with advanced renal cell carcinoma (aRCC) receiving lenvatinib plus pembrolizumab (LEN + PEMBRO) or sunitinib (SUN) in the CLEAR study
Poster Discussion
Abstract #4514
June 4, 2022
5:42 PM EDT

Martin H. Voss, MD
Memorial Sloan Kettering Cancer Center
Gynecologic Cancer Study 309/ KEYNOTE-775 Efficacy of next line of therapy after treatment with lenvatinib (LEN) in combination with pembrolizumab (pembro) versus treatment of physician’s choice (TPC) in patients (pts) with advanced endometrial cancer (aEC): exploratory analysis of Study 309/KEYNOTE-775
Poster Presentation
Abstract #5587
June 4, 2022
2:15 PM EDT

Vicky Makker, MD
Memorial Sloan Kettering Cancer Center
Gastrointestinal Cancers LEAP-014 First-line lenvatinib plus pembrolizumab plus chemotherapy in esophageal squamous cell carcinoma: LEAP-014 trial in progress
Poster Presentation
Abstract #TPS4167
June 4, 2022
9:00 AM EDT

Jong-Mu Sun, MD
Samsung Medical Center, Sungkyunkwan University School of Medicine
MK-6482-016 Phase 2 Open-label Study of Pembrolizumab Plus Lenvatinib and Belzutifan in Patients With Advanced Solid Tumors
Poster Presentation
Abstract #TPS4173
June 4, 2022
9:00 AM EDT

Robin K. Kelley, MD
University of California San Francisco
Lenvatinib
Gastrointestinal Cancer REFLECT Characterization of tumor responses in patients (pts) with unresectable hepatocellular carcinoma (uHCC) treated with lenvatinib in REFLECT
Poster Presentation
Abstract #4078
June 4, 2022
9:00 AM EDT

Masatoshi Kudo, MD
Kindai University Faculty of Medicine
Additional Research
Gynecologic Cancer ECHO EU Treatment Pattern Treatment patterns and outcomes among patients with recurrent or advanced endometrial cancer in Europe: Endometrial Cancer Health Outcomes Europe (ECHO EU) Study
Online Publication
Abstract #e17627
May 26, 2022
5:00 PM EDT

Vimalanand S Prabhu, PhD
Merck & Co., Inc., Rahway, NJ, USA
Genitourinary Cancer Translational Research Exploratory analysis on crosstalk between intra-tumor immunity and FGF/FGFR pathway in clear cell renal cell carcinoma
Online Publication
Abstract #e16525
May 26, 2022
5:00 PM EDT

Takafumi Narisawa, MD
Yamagata University Faculty of Medicine

On May 26, 2022 Aravive, Inc. (Nasdaq: ARAV, "the Company"), a late clinical-stage oncology company developing targeted therapeutics to treat metastatic disease, reported the presentation of updated Phase 1b/2 ccRCC data at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, taking place June 3-7, 2022 in Chicago (Press release, Aravive, MAY 26, 2022, View Source [SID1234615069]). The abstract presents the updated response rate, landmark progression-free-survival data, and biomarker data.

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"We are jubilant about the selection of the poster on the use of batiraxcept in 2L+ ccRCC for oral discussion at this year’s ASCO (Free ASCO Whitepaper) annual meeting," said Gail McIntyre, Ph.D., DABT, Chief Executive Officer of Aravive. "This is a rare opportunity provided only to select abstracts at this meeting. Batiraxcept continues to show best-in-class potential in advanced or metastatic clear cell renal carcinoma, platinum resistant ovarian cancer, and pancreatic cancer. Enrollment in the registration directed Phase 3 program in PROC remains on pace to complete this year and we look forward to providing updates on the renal and pancreatic cancer programs throughout 2022."

Abstract Title: A Phase 1b/2 study of batiraxcept (AVB-S6-500) in combination with cabozantinib in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received front-line treatment (NCT04300140)
Abstract Number: 4511 (Poster Discussion Session – Data will be presented)
Poster Session: Genitourinary Cancer—Kidney and Bladder
Session Date: Poster Presentation: Saturday, June 4, 2022, 1:15 PM – 4:15 PM CDT
Discussion: Saturday, June 4, 2022, 4:30 PM CDT (5:30 PM EDT)

Abstract Title: A Phase 1b/2 study of batiraxcept (AVB-S6-500) in combination with cabozantinib, cabozantinib and nivolumab, and as monotherapy in patients with advanced or metastatic clear cell renal cell carcinoma (NCT04300140)
Abstract Number: TPS4599 (Trials in Progress poster – No data presented)
Poster Session: Genitourinary Cancer—Kidney and Bladder
Session Date: Saturday, June 4, 2022, 1:15 PM – 4:15 PM CDT
Of note, 100% of patients had received a prior immunotherapy, 77% of the patients were in the IMDC (International Metastatic RCC Database Consortium) Risk Score of intermediate or poor, and 39% of the patients had received 2 or more prior lines of therapy prior to study entry.

A summary of the interim Phase 1b results include (as of April 30, 2022, the cut-off date):

Batiraxcept 15 mg/kg in combination with cabozantinib 60 mg has a manageable safety profile in previously treated ccRCC; no dose-limiting toxicities have been observed; a similar safety profile was observed across the 15 mg/kg and 20 mg/kg dose cohorts.
Batiraxcept given every 2 weeks suppressed serum GAS6 to below the level of quantitation in 25/26 patients (1 patient did not have an assessment), showing a clear pharmacokinetic (PK)/pharmacodynamic (PD) relationship; 23/26 patients had batiraxcept trough levels above the minimally efficacious concentration of 13.8 mg/L by Cycle 2.
The confirmed + unconfirmed response rate in the total population was 46% with a 50% confirmed response rate in the 15mg/kg (RP2D) batiraxcept group.
The proportion of patients in the total population who were progression free at 7 months was 71%.
The proportion of patients in the total population who had a duration of response of at least 7 months was 75%.
A baseline biomarker enriched the confirmed response rate in the RP2D (15mg/kg) biomarker high population to 67%, increased the proportion of patients progression free at 7 months to 91% and increased the proportion of patients who had a duration of response of at least 7 months to 80%.
58% (15/26) of total population achieved a better response on the batiraxcept trial than they did with their therapy prior to study entry, which was only 23%.
The safety and clinical activity of this combination together with PK/PD data support a RP2D of 15 mg/kg.

On May 26, 2022 Heron Therapeutics, Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company focused on improving the lives of patients by developing and commercializing therapeutic innovations that improve medical care, reported that company management will participate in a fireside chat at the 2022 Jefferies Global Healthcare Conference on Wednesday, June 8, 2022 at 8:30 am ET (Press release, Heron Therapeutics, MAY 26, 2022, View Source [SID1234615086]). The conference is taking place June 8-10th, 2022 in New York, NY.

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A live webcast of the fireside chat will be available on the Company’s website at www.herontx.com in the Investor Resources section.