On May 13, 2020 I-Mab (NASDAQ: IMAB), a clinical stage biopharmaceutical company committed to the discovery, development and commercialization of novel or highly differentiated biologics to treat diseases with significant unmet medical needs, reported that the first patient has been dosed in a Phase 1/2 clinical study in China to evaluate I-Mab’s proprietary CD73 antibody TJD5, also known as TJ004309, in patients with advanced solid tumors (CTR20200445; NCT04322006) (Press release, I-Mab Biopharma, MAY 13, 2020, View Source [SID1234557901]).

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"It’s exciting news that the TJD5 study has been initiated in China. TJD5 represents a promising novel compound targeting the cancer microenvironment. This could bring new hopes to the patients if safety and efficacy could be demonstrated," said Professor Yi-Long Wu, Tenured Professor of Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, South China University of Technology, Chair of Chinese Thoracic Oncology Group.

This Phase 1/2 study is a multicenter, open-label, dose escalation and cohort expansion study, which will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of TJD5, and determine a recommended dose for further clinical studies of its efficacy and safety as a single agent and in combination with standard dose of toripalimab (TUOYI ) in patients with advanced or metastatic cancers who are refractory to or intolerant of all available therapies.

"We are pleased to advance TJD5 into the clinical study in China and are committed to realizing the potential of TJD5 as a next-generation immuno-oncology agent," said Dr. Joan Shen, M.D., Ph.D., CEO of I-Mab. "We have been able to accelerate the Phase 1/2 trial in China by leveraging data from the ongoing Phase 1 clinical study of TJD5 in the United States, which is a testament to our global clinical development capabilities and well-executed pipeline strategies."

"The low response rates to PD-1/PD-L1 inhibitor treatments in cancer patients remain a significant unmet clinical need. As CD73 is widely expressed in various cancers, we hope the combination therapy of TJD5 with toripalimab could provide a potential new transformational treatment option for patients in need," Dr. Shen added.

I-Mab entered into a research collaboration with Junshi Biosciences (HKEX:01877) in September 2019 to evaluate TJD5 in combination with toripalimab (TUOYI) for the treatment of patients with cancers in China.

About TJD5 (TJ004309)

TJD5 is a differentiated, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine. Adenosine binds adenosine A2A and A2B receptors on immune cells and inhibits immune responses directed against tumors. TJD5 is expected to suppress the immunosuppressive tumor micro-environment and to work in concert with other cancer therapies such as PD-1 and PD-L1 antibodies. TJD5 exerts anti-tumor activities through a unique intra-dimerization mechanism to completely inhibit the activity of the targeted enzyme as evident in preclinical studies.

TJD5 is also in a Phase 1 clinical trial in the US to assess the tolerability and preliminary efficacy as a single agent and in combination with atezolizumab (TECENTRIQ), a PD-L1 antibody marketed by Roche, in patients with advanced solid tumors.

On May 13, 2020 The ECOG-ACRIN Cancer Research Group reported that the final results of the randomized phase two trial E3311 will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, to occur virtually from May 29-31 (Press release, ECOG-ACRIN, MAY 13, 2020, View Source [SID1234557899]). The trial, conducted in patients undergoing transoral robotic surgery (TORS), tested reduced postoperative radiation therapy in patients with human papillomavirus-associated oropharynx squamous cell carcinoma at intermediate risk for recurrence. ASCO (Free ASCO Whitepaper) is highlighting the importance of the positive results by making it the first presentation in its Head and Neck Oral Abstract Session (Abstract 6500). The ECOG-ACRIN Cancer Research Group designed and conducted the trial with funding from the National Cancer Institute, part of the National Institutes of Health.

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"Transoral resection followed by low-dose radiation is safe in patients with intermediate-risk locally advanced oropharynx cancer, with very good oncologic outcome," said lead investigator Robert L. Ferris, MD, PhD, director, UPMC Hillman Cancer Center in Pittsburgh and a surgical oncologist specializing in head and neck cancer (pictured). "These results present a promising deintensification approach."

Most pharynx cancers caused by HPV have a very good outcome, and the cancer does not return or spread to other parts of the body after treatment. Dr. Ferris and colleagues sought to prove the benefits of using tumor pathologic features, obtained in specimens collected at surgery, to determine patients’ risk of recurrence–low, intermediate or high. In particular, they sought to more clearly define the prognostic and predictive role of traditional pathologic biomarkers such as extensive nodal or extranodal disease, to give the right amount of postoperative treatment for each risk group.

Patients at low risk were observed. Patients at intermediate risk were randomized to two arms of radiation alone, both at doses lower (50Gy or 60Gy) than usual (60-66Gy). At the time the trial opened in 2013, the optimal dose of radiation therapy was not defined. Patients at high risk were assigned to usual radiation therapy plus chemotherapy.

"Study E3311 met its primary endpoint," said Dr. Ferris. "For intermediate risk patients–those with uninvolved surgical margins, less than five involved nodes, and less than 1mm extranodal extension–reduced-dose postoperative radiation therapy without chemotherapy appears sufficient. In our study, this group had better outcomes than the group on usual high-dose radiation plus chemotherapy, showing that our patient stratification identified low and intermediate risk patients well, preserving patients’ throat function and sparing them unnecessary short- and long-term toxicities."

For patients with low-risk disease, two-year progression-free survival (PFS) was favorable without postoperative therapy (observation alone). All arms had two-year survival rates above 90% and there was no excess of local recurrences with reduction in radiation or chemotherapy (Arms B and C). Risk stratification appeared to appropriately select patients for observation (Arm A).

The overall intent of E3311 was to gather essential data for the design of a future, randomized phase three trial. The primary endpoint was to determine the feasibility and oncologic efficacy of a prospective multi-institutional study of TORS for HPV+ oropharynx cancer followed by risk-adjusted adjuvant therapy. The primary endpoint was two-year progression-free survival in patients determined to be at intermediate risk after surgical excision.

"The tissue samples and imaging studies collected in the course of this trial are a rich resource for studying the biology of intermediate- and high-risk disease, in work that is ongoing," said ECOG-ACRIN Head and Neck Committee Chair, Barbara A. Burtness, MD, Professor of Medicine, and Co-Leader, Developmental Therapeutics Program, Yale Cancer Center and Yale School of Medicine (pictured). "ECOG-ACRIN plans to pursue the current data with a randomized phase three trial of TORS-based treatment deintensification compared with conventional chemoradiation."

A lump in the neck and a sore throat are the most common signs of oropharynx cancer, a disease in which cancer cells form in the tissues of the oropharynx–the middle part of the throat (pharynx), at the base of the tongue and tonsils. About 60% of oropharynx cancers are associated with HPV infection. The incidence has been increasing in recent years, especially in individuals under the age of 45. This change is attributed to the increasing prevalence of HPV infection in developed countries, the practice of oral sex, and the rising number of sexual partners.

While surgeons and patients widely favor the organ-preservation approach of transoral robotic surgery, there remain serious concerns about both short- and long-term toxicities associated with chemotherapy. Besides, given the potential long-term consequences of radiation therapy for a younger population, re-evaluation of adjuvant treatment intensity is needed.

On May 13, 2020 An Upstate Medical University urology professor reported that it has been awarded a grant from the Department of Defense (DOD) to continue and advance his research on kidney cancer (Press release, SUNY Upstate, MAY 13, 2020, View Source [SID1234557898]).

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The grant will support work by Mehdi Mollapour, PhD, vice chair for translational research for the department of urology, and his lab as it continues a decade-long research project into understanding kidney cancer biology and to develop novel therapeutic strategies to treat patients. Mollapour, professor of urology, molecular biology and biochemistry, is also the director of kidney cancer biology at Upstate.

His work, published in high-impact-factor journals (Dushukyan et al, 2017, Cell Reports & Oberoi et al, Proceedings of the National Academy of Sciences, 2016) identified a prosurvival role for PP5 protein in kidney cancer. Mollapour’s lab is currently funded by several grants from the National Institutes of Health and the National Cancer Institute. He applied for this DOD grant last fall and was notified of the award this spring.

"It’s always exciting when any grant is funded," he said. "From small amounts to big amounts, to have the funds to be able to continue our work and pay students and pay researchers is exciting."

About 74,000 Americans will be diagnosed with kidney cancer in 2020, according to the American Cancer Society. The disease is more common in men and kills nearly 15,000 people in the U.S. each year, according to the ACS.

In the application for the DOD grant, Mollapour’s lab cites a higher risk for developing kidney cancer among military families because of environmental exposures. The application also talks about what a difficult disease it can be to treat, highlighting the need to seek biomarkers for early detection and new therapies like those being developed in Mollapour’s lab. Traditional radiation and chemotherapies are ineffective in patients with kidney cancer and when presenting with large or locally advanced tumors, about 50 percent develop metastatic disease, for whom the five-year survival rate is less than 20 percent, according to the application.

The most recent grant – Mollapour’s first from the DOD – will propel the lab’s work and continue to open doors for additional funding.

"The grant allows us to better understand this disease and new ways of treating it. Naturally, data generated here will enable us to obtain further funding," he said. The $400,000 grant will support research staff, including students, working in the lab for two years. He and his staff are actively applying for additional funding from the National Institutes of Health.

Mollapour credits the work of everyone in his lab for obtaining this grant. After learning the good news about the DOD funding, Mollapour said he does what he always does when he is notified of new grant funding – he calls Upstate Chair of Urology Gennady Bratslavsky, MD, on the phone and plays the song "We Are The Champions," by Queen over the phone.

"When he hears that he knows what happened," Mollapour said laughing. "We have a secret code and Bratslavsky gets equally excited because he appreciates the importance of research and that is why he is fully committed in supporting research."

Mollapour and Bratslavsky worked together before coming to Upstate.

"Dr. Mollapour is a brilliant scientist and I take great pride in being able to recruit him from the National Cancer Institute where we both worked in urologic oncology studying kidney cancer," Bratslavsky said. "I respect Dr. Mollapour’s talent in research, his perseverance and his ability to be a mentor for many of my students and residents."

Mollapour said this grant is exciting and important because of its direct connection to patient care and its potential to extend the lives of kidney cancer patients.

"I know whatever we are going to do in terms of research will directly impact the kidney cancer patient," he said. "This is not one of those types of research that is 10 steps away from helping the patient. This is so gratifying and very exciting. The patient is always on my mind. It might be cliché but I really think we will help the patients with this. We are going to make it happen one way or another."

On May 13, 2020 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported updated safety and initial efficacy data contained in an abstract scheduled as an oral presentation at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, to be held May 29–31, 2020 (Press release, Arvinas, MAY 13, 2020, View Source [SID1234557897]). The presentation will share updated data from the dose escalation portion of Arvinas’ Phase 1/2 clinical trial of ARV-110 in men with metastatic castration-resistant prostate cancer. The abstract describes two patients with ongoing confirmed prostate-specific antigen (PSA) responses, including one with an unconfirmed partial tumor response.

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"We are thrilled to present the first evidence that our PROTAC protein degrader, ARV-110, can provide clinical efficacy," said John Houston, Ph.D., President and Chief Executive Officer at Arvinas. "This is a significant milestone for our technology platform and for the field of targeted protein degradation."

"While still early, we are pleased to see a safety profile to date for ARV-110 that continues to support dose escalation," added Ron Peck, M.D., Chief Medical Officer at Arvinas. "Our trial of ARV-110 has enrolled a particularly heavily pre-treated population of patients who have exhausted most available treatment options. Most patients received both enzalutamide and abiraterone as well as prior chemotherapy. Despite this, ARV-110 demonstrated the first evidence of antitumor activity in this difficult-to-treat patient population."

The presentation will include data collected since the abstract submission date. Dose escalation continues, with enrollment initiated above the previously disclosed daily dose of 280 milligrams.

Abstract details are as follows:
Presentation Title: First-in-human phase I study of ARV-110, an androgen receptor PROTAC degrader in patients with metastatic castrate-resistant prostate cancer following enzalutamide and/or abiraterone
Abstract Number: 3500
Session Type: Oral Abstract Session
Session Track: Development Therapeutics – Molecularly Targeted Agents and Tumor Biology

For a copy of the abstract, please visit ASCO (Free ASCO Whitepaper)’s official website.

About ARV-110
ARV-110 is an orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). ARV-110 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.

About Metastatic Castration-Resistant Prostate Cancer (mCRPC)
In the United States, prostate cancer is both the second most prevalent cancer in men and the second leading cause of cancer death in men. The American Cancer Society predicts that one in nine men will be diagnosed with prostate cancer in his lifetime. Metastatic castration-resistant prostate cancer (mCRPC) is defined by disease progression despite androgen deprivation therapy and is often correlated with rising levels of prostate-specific antigen (PSA).

Current AR-targeted standard of care treatments for mCRPC are less effective in patients whose disease has increased levels of androgen production, AR gene or gene enhancer amplification, or AR point mutations. Up to 25 percent of patients do not respond to second-generation hormone therapies like abiraterone and enzalutamide, and the vast majority of responsive patients will ultimately become resistant, resulting in poor prognoses for men diagnosed with this devastating condition.

On May 13, 2020 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) therapies for cancer, in collaboration with its development partner Servier, an independent international pharmaceutical company, reported the release of the abstract related to an upcoming oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Allogene, MAY 13, 2020, View Source [SID1234557896]). This will be the first data from Allogene’s Phase 1 dose escalation ALPHA study of ALLO-501 in relapsed/refractory non-Hodgkin lymphoma (NHL). This study utilizes ALLO-647, Allogene’s anti-CD52 monoclonal antibody (mAb), as a part of its differentiated lymphodepletion regimen.

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"As we look ahead to the end of the month to the virtual ASCO (Free ASCO Whitepaper) meeting, we are excited to present initial clinical data from our first-in-human study of ALLO-501 and ALLO-647," said Rafael G. Amado, M.D., Executive Vice President of Research & Development and Chief Medical Officer of Allogene. "These findings will provide an early glimpse into the potential of our AlloCAR T pipeline and ALLO-647 based lymphodepletion strategy, which we believe will be foundational in driving the future success and broad applicability of AlloCAR T therapies."

The ASCO (Free ASCO Whitepaper) abstract includes preliminary data on the first nine patients treated with escalating doses of ALLO-501 and lower dose (39mg) ALLO-647. No dose limiting toxicities or graft-vs-host disease (GvHD) was observed. The most common Grade (Gr) ≥ 3 adverse events were neutropenia (55.6%), leukopenia (33.3%) and anemia (22.2%). Two patients (22.2%) developed cytokine release syndrome (one Gr1 and one Gr2) that resolved within 72 hours without steroids or tocilizumab. One patient developed Gr1 neurotoxicity that resolved without treatment. One patient developed upper respiratory tract infection (Gr2), CMV (Gr3) and EBV viremia (Gr1), which all resolved. One patient had a Gr2 infusion reaction to ALLO-647 which resolved with antihistamines.

In this limited dataset with a small number of patients, the overall response rate (ORR) was 78% (95% exact CI: 40%, 97%) with three complete responses (CR) and four partial responses (PR). As of the January 2020 data cutoff, there was a median follow up of 2.7 months with four patients in ongoing response and three patients having progressed at 2, 4 and 6 months.

The virtual presentation will include data on 11 patients across ALLO-501 cell dose cohorts and the lower dose (39mg) of ALLO-647, as well as additional patients treated with ALLO-501 and the higher dose (90mg) of ALLO-647. The Phase 1 ALPHA study continues to enroll patients with higher dose ALLO-647 in an effort to optimize lymphodepletion.

This virtual presentation will be available on demand when ASCO (Free ASCO Whitepaper) releases pre-recorded presentations on May 29, 2020 at 5:00 a.m. PT/8:00 a.m. ET. Allogene will also host a conference call on May 29th following the release of the presentation.

Oral Abstract Session: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia
Abstract #8002
Title: First-in-Human Data of ALLO-501 and ALLO-647 in Relapsed/Refractory Large B-cell or Follicular Lymphoma (R/R LBCL/FL): ALPHA Study.
Presenter: Sattva S. Neelapu, MD, The University of Texas MD Anderson Cancer Center, Department of Lymphoma/Myeloma, Houston, TX
Session Release Date & Time: May 29, 2020 at 5:00 a.m. PT/8:00 a.m. ET
Location: On demand virtual presentation

Allogene is the sponsor of this Phase 1 trial which is designed to assess the safety and tolerability at increasing dose levels of ALLO-501 and ALLO-647 in patients with relapsed/refractory diffuse large B-cell lymphoma and follicular lymphoma.

Allogene expects to initiate enrollment in ALPHA2, a Phase 1 trial with abbreviated dose escalation of ALLO-501A, in Q2 2020. ALLO-501A is the next generation of ALLO-501, which eliminates the rituximab recognition domains, and it is intended for Phase 2 development.

About ALLO-501 (Allogene Sponsored)
Allogene’s AlloCAR T programs utilize Cellectis technologies. ALLO-501 is an anti-CD19 allogeneic CAR T (AlloCAR T) therapy being jointly developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. Servier grants to Allogene exclusive rights to ALLO-501 in the U.S. while Servier retains exclusive rights for all other countries.