City of Hope to Present Leading-Edge Radiotherapy Treatments for People with Lung, Genitourinary and Blood Cancers at the American Society for Radiation Oncology Annual Meeting

On September 30, 2024 City of Hope, one of the largest and most advanced cancer research and treatment organizations in the U.S. and ranked among the nation’s top 5 cancer centers by U.S. News & World Report, reported that it is part of today’s press conference program at the American Society for Radiation Oncology (ASTRO) Annual Meeting, where a renowned City of Hope radiation oncologist will present phase 3 clinical trial data showing that people with limited-stage small cell lung cancer may benefit from adding immunotherapy to chemoradiation, but not if both treatments are given at the same time (Press release, City of Hope, SEP 30, 2024, View Source [SID1234646956]). The results suggest that the timing of when immunotherapy is given plays a key role in its ability to extend survival.

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"The introduction of immunotherapy marked the first significant breakthrough in treating small cell lung cancer treatment in decades. Now, we see that if you give immunotherapy concurrently with chemoradiation, it does not yield the same survival benefit as it does when we add it after standard treatment," said lead author Kristin Higgins, M.D., a radiation oncologist, clinical professor and chief clinical officer at City of Hope Cancer Center Atlanta.

Dr. Higgins is presenting the late-breaking abstract at a 10 a.m. ET press conference today in room 103A of the Walter E. Washington Convention Center in Washington, D.C.; the scientific plenary will take place at 2:10 p.m. ET in Ballroom A/B/C.

ASTRO is the world’s largest radiation oncology society, with more than 10,000 members. Radiation therapy contributes to 40% of global cancer cures, and more than 1 million Americans receive radiation treatments for cancer each year.

Lung cancer is the leading cause of cancer deaths in the U.S. An aggressive form of the disease is small cell lung cancer, which accounts for 10-15% of all lung cancers. Standard treatment for patients with limited-stage disease that has not spread outside the chest and is potentially curable includes concurrent radiation therapy and chemotherapy. While treatments can be effective initially, the cancer often recurs and options for additional treatment have historically been limited.

Dr. Higgins and her colleagues randomized 544 patients at centers across the U.S. (n=500) and Japan (n=44) to receive standard chemoradiation with or without atezolizumab immunotherapy. All patients received radiation therapy either twice daily or once daily as well as four cycles of concurrent chemotherapy. For patients on the experimental arm, atezolizumab was also given every three weeks beginning at the start of radiation, for a maximum of one year.

Contrary to expectations, concurrent treatment with atezolizumab and chemoradiation did not improve survival rates compared to standard care. The lack of survival benefit when giving immunotherapy together with chemoradiation, rather than after radiation is completed, indicates that the activity of this type of immunotherapy is reduced when given simultaneously with thoracic radiation, likely due the inherent immunosuppressive effects of radiation, Dr. Higgins explained.

"We know that radiation suppresses the immune system to a certain degree in the immediate sense, and immunotherapy relies on the immune system to be effective," she said. "Adding these drugs after you give radiation can make the immunotherapy more potent, but you have to allow the immune system time to recover to really see the two work well together."

There was a benefit to giving radiation twice daily over giving it once daily, regardless of study arm. In both groups, patients treated twice daily lived longer on average; median overall survival for those treated twice daily was 35.4 months, compared to 28.3 months for people treated once per day.

"Sometimes, if you give too much therapy at the same time, it actually yields worse outcomes. And this trial demonstrated that. But at the same time, we did see that changing the way you give radiation can help," Dr. Higgins said, noting that City of Hope continues to be at the forefront of a powerful form of immunotherapy known as chimeric antigen receptor (CAR) T cell therapy. City of Hope researchers are among the scientists working to develop and test new lung cancer immunotherapy treatments.

Other world-renowned City of Hope physicians and researchers also will present new data and offer expert perspectives on leading-edge cancer research and treatments in development.

Is biology-guided radiotherapy an option for people with prostate cancer?

Presentation time and location: Monday, Sept. 30, from 3:50 to 4 p.m. ET in Room 145

City of Hope was the first in Southern California and among the first in the nation to adopt a type of biology-guided radiotherapy called SCINTIX therapy that later in 2023 was cleared by the U.S. Food and Drug Administration. This study, led by Chunhui Han, Ph.D., City of Hope clinical professor of radiation oncology, included prostate cancer patients and resulted in the development of a comprehensive set of screening criteria to identify people who would benefit from this leading-edge, personalized radiation oncology treatment. City of Hope aims to develop efficient protocols so that other institutions one day can also implement the SCINTIX therapy on the RefleXion X1.

Phase 2 trial with leukemia patients could lead to radiotherapy that attempts to bypass harm to organs

Presentation time and location: Monday, Sept. 30, from 5:10 to 5:20 p.m. ET in Room 144

In a phase 2 trial noted as the largest prospective study using total marrow and lymphoid irradiation (TMLI), Jeffrey Wong, M.D., City of Hope professor of radiation oncology, Anthony Stein, M.D., and colleagues treated 74 patients with either acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) with TMLI, which delivers targeted radiation to bone marrow while reducing negative impact to organs. The team developed a regimen that could be an effective hematopoietic cell transplant option for AML and ALL patients with recurrent cancer or disease that has become resistant to treatment. The regimen is currently under evaluation as a potential replacement for standard total body irradiation conditioning in patients with AML who are in complete remission. City of Hope’s bone marrow and blood stem cell transplant program is the largest in the country; its doctors have performed nearly 20,000 transplants to date.

Study evaluating effectiveness of pre-transplant radiotherapy that limits toxicity to organs

Presentation time and location: Tuesday, Oct. 1, from 1:25 to 1:35 p.m. ET in Room 144

Colton Ladbury, M.D., City of Hope assistant professor of radiation oncology, led the largest study to date reporting long-term toxicities resulting from total marrow irradiation (TMI) and total marrow and lymphoid irradiation (TMLI), both of which are used to prepare patients for a stem cell transplant. Some 302 patients with multiple myeloma or acute leukemia were followed for up to eight years with median follow-up of 6.3 years in living patients. They found that TMI/TMLI is associated with lower rates of pulmonary toxicity, renal toxicity and hypothyroidism compared with historical cohorts treated with conventional total body irradiation.

Dr. Ladbury is one of 12 residents in the world to receive an ASTRO recognition award for his quick pitch oral. The award is designed to highlight excellence among peers at the largest annual meeting of radiation oncologists from around the globe.

A potentially better way to deliver radiotherapy and chemotherapy to people with lung cancer

Presentation time and location: Tuesday, Oct. 1, from 1:25 to 1:35 p.m. ET in Room 147

In an early-phase trial, researchers led by Percy Lee, M.D., City of Hope professor of radiation oncology, found that it is safe and effective to treat patients with locally advanced, inoperable non-small cell lung cancer using chemoradiation via a dose-escalated adaptive stereotactic ablative radiotherapy boost in 15 sessions of radiation instead of the standard 30 sessions as they also receive chemotherapy.

Using AI to evaluate immune system response

Presentation time and location: Tuesday, Oct. 1, from 1:25 to 1:35 p.m. ET in Room 152

Immuno-positron emission tomography (ImmunoPET) allows for spatial evaluation of white blood cell distributions. William Tyler Watkins, Ph.D., physicist and City of Hope associate clinical professor, led a research team that leveraged artificial intelligence (AI) to segment the human body and evaluate CD8+ T cell concentrations before and after radiation therapy. The model was validated using data from five patients in an ongoing clinical trial and identifies varying patient-specific immune system response following radiation treatment.

Novel theranostic PET imaging agent for patients with advanced rectal cancer

Presentation time and location: Tuesday, Oct. 1, from 5:15 to 5:25 p.m. ET in Room 152

In an ongoing pilot study, Jeffrey Wong, M.D., City of Hope professor of radiation oncology, and colleagues found that a radioactive molecule attached to a monoclonal antibody (Cu-64-Anti-CEA M5A) shows promise as a theranostic — therapy plus diagnostic — tool that allows experts to identify disease sites in patients with rectal cancer. It also shows promise as a way to assess response to chemotherapy and radiotherapy received before cancer treatment, such as surgery. More research is needed to fully understand this therapeutic’s disease targeting and efficacy capabilities.

The below oral presentations have already been presented.

A promising treatment regimen for prostate cancer patients

Presentation time and location: Sunday, Sept. 29, from 8:30 to 8:40 a.m. ET in Room 207B

Early data from an ongoing phase 2 trial led by Savita Dandapani, M.D., Ph.D., City of Hope associate professor of radiation oncology, suggests that a promising treatment regimen for patients with metastatic castration-sensitive prostate cancer is radium 223 dichloride (Ra-223) combined with stereotactic body radiation therapy delivered to tumors that have spread to bone. The treatment plan should include 36 weeks of androgen deprivation therapy combined with the radiation. This is an early trial to show that the use of systemic radiation (radiopharmaceuticals) with stereotactic body radiation treatment may help prevent progression of micrometastases.

A new way to determine the strength of phase 3 cancer clinical trials

Presentation time and location: Sunday, Sept. 29, from 5:05 to 5:15 p.m. ET in Room 207B

A team of researchers led by Yufei Liu, M.D., Ph.D., City of Hope assistant clinical professor of radiation oncology, developed a benchmark to assess the strength of phase 3 clinical trials. They evaluated a database of 332 phase 3 oncology trials and found that targeted therapy trials, trials with progression-free survival as a final endpoint and positive trials tend to have the most robust, reproducible data. More work needs to be done to validate the developed benchmark, which could then be leveraged to design better clinical trials.

Repare Therapeutics Announces Phase 1 Data Highlighting Camonsertib in Combination with Radiotherapy Treatment Presented at the ASTRO Annual Meeting

On September 30, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported data highlighting the clinical benefits of camonsertib, a potential best-in-class oral small molecule ATR inhibitor, combined with palliative radiation for the treatment of metastatic tumors harboring an ataxia-telangiectasia-mutated (ATM) mutation (Press release, Repare Therapeutics, SEP 30, 2024, View Source [SID1234646955]).

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These data from a clinical trial conducted in collaboration with investigators at Memorial-Sloan Kettering Cancer Center were presented at the American Society for Radiation Oncology (ASTRO) annual meeting in Washington, DC by Nancy Lee, MD, FASTRO, Radiation Oncologist & Early Drug Development Specialist, Memorial Sloan Kettering Cancer Center and titled, "Genotypically-Selected Pan Cancer Trial of Camonsertib with Palliative Radiation in the Treatment of Metastatic Tumors Harboring an Ataxia-Telangiectasia Mutated (ATM) Mutation."

"These encouraging early Phase 1 data build further support for the broad clinical potential of camonsertib," said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. "This first-in-human study combining camonsertib, an ATR inhibitor, with palliative radiation provides early clinical data showing that the combination has the potential to radiosensitize for higher clinical benefit in patients with tumors harboring pathogenic ATM mutations versus those with variants of unknown significance. We are highly encouraged by this early look at the response rate and safety profile of this combination in the Phase 1 setting."

Key Study Findings

Seventeen (17) patients with metastatic tumors harboring ATM mutations were enrolled in the trial; of which 12 had pathogenic ATM mutations and 5 had ATM mutations with variants of unknown significance (VUS).
Primary cancer histology included gastrointestinal (n=5), pancreas (n=5), breast (n=2), lung (n=2), bladder (n=2), and thyroid (n=1).
The recommended phase 2 dose for camonsertib was determined to be 160 mg given once-daily prior to radiation (4Gy) on days 1-5.
Interim response information was available for 16 patients at submission:
At 2-months, there were 2 complete responses (CR), 5 partial responses (PR), and 4 stable disease (SD) in the pathogenic ATM mutation group versus 1 PR and 4 SD in the VUS group.
At 6-months, in 9 evaluable patients, 2 CR, 4 PR, and 1 SD were reported in the pathogenic group versus 1 SD and 1 progressive disease (PD) in the VUS group.

Adicet Bio to Present at the American Society of Gene & Cell Therapy’s (ASGCT) 2024 Advancing Gene + Cell Therapies for Cancer Conference

On September 30, 2024 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, reported acceptance of an oral presentation at the upcoming American Society of Gene & Cell Therapy’s (ASGCT) (Free ASGCT Whitepaper) 2024 Advancing Gene and Cell Therapies for Cancer conference, taking place October 16 – 17, 2024, in Philadelphia, PA (Press release, Adicet Bio, SEP 30, 2024, View Source [SID1234646954]).

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Details of the oral presentation are as follows:

Title: ADI-270: An Armored Allogeneic Anti-CD70 CAR γδ T cell Therapy Designed for Enhanced Potency and Persistence Against Multiple Oncology Indications
Session Name: Novel Targets and Effector Cells
Abstract Number: 8
Presenting Author: Shon Green, Ph.D.
Date and Time: October 17, 2024; 11:15 a.m. – 11:30 a.m. ET

Akeso’s Cadonilimab Receives Second Indication Approval from NMPA for First-Line Treatment of Gastric/GEJ Cancer in All-Comers Population

On September 30, 2024 Akeso (9926. HK) reported that its internally developed PD-1/CTLA-4 bispecific antibody, cadonilimab, has received approval from the National Medical Products Administration (NMPA) for a new indication: cadonilimab in combination with fluoropyrimidine and platinum-based chemotherapy for first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (Press release, Akeso Biopharma, SEP 30, 2024, View Source [SID1234646953]). This is the second indication approval for cadonilimab in China, following its initial approval for marketing in June 2022.

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The approval of the new indication for cadonilimab combination therapy for first-line treatment of gastric/GEJ cancer is based on the COMPASSION-15/AK104-302 study. In the COMPASSION-15 study, the proportion of patients with PD-L1 CPS < 5 and PD-L1 CPS < 1 in the Intention-to-Treat (ITT) population reached 49.8% and 23%, respectively, which is significantly higher than the data disclosed in previous phase III studies of other immunotherapies for first-line treatment.

In November 2023, the interim analysis of the study achieved the primary endpoint of overall survival (OS). The results showed that the cadonilimab combination therapy significantly reduced the risk of death in advanced gastric cancer patients across all PD-L1 expression levels (including those with PD-L1 CPS ≥5 and <5), extending overall survival benefits and demonstrating notable advantages in objective response and long-term survival. Previous phase III trials of PD-1 inhibitors combined with chemotherapy showed limited or no clinical benefit for patients with low or negative PD-L1 expression.

The results of the COMPASSION-15 study were presented as an oral report at the 2024 AACR (Free AACR Whitepaper). In the ITT population, the median overall survival (mOS) for the cadonilimab regimen reached 15.0 months, compared to 10.8 months in the control group, extending overall survival by 4.2 months and reducing the risk of death by 38% (HR=0.62). In the PD-L1 CPS <5 group, the mOS for the cadonilimab regimen was 14.8 months, with a 30% reduction in the risk of death compared to the control group (11.1 months, HR=0.70). For the PD-L1 CPS ≥5 group, the mOS had not yet been reached, but the risk of death was reduced by 44% compared to the control group (10.6 months, HR=0.56).

COMPASSION-15’s principal investigator, Professor Ji Jiafu from Peking University Cancer Hospital, stated:

" The prognosis for advanced gastric cancer is poor. While currently approved immunotherapy options have improved efficacy compared to traditional chemotherapy, there remains significant potential for enhancement. The cadonilimab combination therapy has substantially increased the objective response rate and overall survival in the general population while reducing disease-related mortality. Remarkably, cadonilimab shows significant overall survival benefits not only in patients with high PD-L1 CPS expression but also in those with low or negative PD-L1 CPS expression.

The approval of cadonilimab as a first-line treatment effectively addresses the efficacy gap of PD-1/L1 monoclonal antibodies in patients with low or negative PD-L1 expression, providing a more comprehensive and effective immunotherapy option for advanced gastric cancer. This advancement benefits all patient populations and presents new opportunities for the global development of gastric cancer immunotherapy, carrying important clinical implications.

As a clinician, I am enthusiastic about the approval of cadonilimab for advanced gastric cancer. This innovative treatment will offer a superior and more comprehensive immunotherapy option for patients, and I look forward to its impact on optimizing the current clinical landscape for advanced gastric cancer."

COMPASSION-15’s principal investigator, Professor Shen Lin from Peking University Cancer Hospital, stated:

"We are delighted by the successful approval of cadonilimab combination therapy for the first-line treatment of advanced gastric cancer. This regimen offers significant advantages over current immunotherapy options in clinical practice, providing a superior choice not only for patients with high PD-L1 expression but also for those with low or negative PD-L1 expression, who previously lacked effective treatment options.

Cadonilimab addresses the limitations of single-target immunotherapy and exemplifies the synergistic mechanism of dual immune therapy with "anti-PD-1 + anti-CTLA-4," thereby filling an important clinical gap in the treatment of advanced gastric cancer. Beyond first-line approval, the phase III clinical study (AK109-301) of cadonilimab combined with pulocimab (AK109, VEGFR-2) for treating advanced gastric cancer that has progressed after PD-1/L1 inhibitor plus chemotherapy has been initiated. There is currently a lack of effective standard treatments for patients with acquired resistance to immunotherapy, and we eagerly anticipate that this new combination regimen will yield improved results in second-line therapy for these patients, ultimately providing clinicians with more effective tools for cancer treatment."

Dr. Xia Yu, Founder, Chairwoman, President, and Chief Executive Officer of Akeso Biopharma, stated:

"We thank all researchers, participants, and patients involved in this clinical study. Their collective efforts have led to the approval of cadonilimab combination therapy for first-line treatment of advanced gastric cancer, introducing a novel bispecific immune therapy combined with chemotherapy.

As immunotherapy evolves, global regulators and the medical community are reassessing the real-world benefits of PD-1 therapies across different PD-L1 expression levels in gastric and esophageal cancers.

Cadonilimab, a novel bispecific antibody targeting both PD-1 and CTLA-4, is supported by robust evidence demonstrating significant clinical benefits for the entire gastric cancer population. Differentiating from PD-1 monoclonal antibody combinations, cadonilimab also shows substantial advantages for patients with low or negative PD-L1 expression. Akeso will continue to explore the global clinical value of cadonilimab."

Gastric cancer is one of the most common malignant tumors worldwide. According to the International Agency for Research on Cancer (IARC) 2022 statistics, there are nearly one million new cases each year, making it the fifth most common cancer. China accounts for about half of these cases and deaths, with HER2-negative patients representing around 88%. For those ineligible for surgery or with metastatic gastric cancer (including gastroesophageal junction cancer), immunotherapy using PD-1/L1 monoclonal antibodies has shown success in first-line treatment, though survival benefits remain limited. Cadonilimab combination therapy is expected to provide a more effective treatment option.

Regor Enters into a Definitive Purchase Agreement for Genentech to Acquire Regor’s Portfolio of next-generation CDK inhibitors for the Treatment of Breast Cancer

On September 30, 2024 Regor Pharmaceuticals (USA) ("Regor") reported that it has entered into a definitive purchase agreement whereby Genentech, a member of the Roche Group, will acquire a portfolio of next-generation CDK inhibitors from Regor for the treatment of breast cancer (Press release, Regor Therapeutics, SEP 30, 2024, View Source [SID1234646951]).

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Under the terms of the agreement, Regor will receive an upfront cash payment of $850 million and is eligible to receive additional cash payments based on the achievement of certain predetermined development, regulatory and commercial milestones. Genentech will be responsible for clinical development, manufacturing and commercialization worldwide. Regor will continue to manage the two ongoing Phase 1 trials to their completion: Regor will also advance its other distinct assets, unrelated to this deal, in oncology, metabolic diseases and auto-immunity.

"Genentech is well-positioned to bring these novel therapeutics to their full potential to benefit patients with breast cancer around the world," said Xiayang Qiu, Ph.D., founder and CEO of Regor. " We are proud of the strong data we have generated to date. We look forward to bringing more innovative therapies to patients around the world."

The proposed transaction is expected to close in the fourth quarter of 2024. The closing of the proposed transaction is subject to the satisfaction of customary closing conditions.

BofA Securities, Inc. is acting as the exclusive financial advisor to Regor on this transaction, and Cohen, Tauber Spievack & Wagner PC and DLA Piper are its legal advisors.