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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

Anixa Biosciences Announces Submission of Protocol Amendment for CAR-T Trial

On September 30, 2024 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer, reported that it and partner Moffitt Cancer Center ("Moffitt") have submitted an amendment to the current protocol that governs its ongoing clinical trial utilizing a CAR-T therapy to treat ovarian cancer (NCT05316129) (Press release, Anixa Biosciences, SEP 30, 2024, https://ir.anixa.com/news/detail/1052/anixa-biosciences-announces-submission-of-protocol-amendment-for-car-t-trial [SID1234646922]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A key change in the protocol provides a second dose of the therapy to patients who might benefit from an additional dose. Previously, Anixa and Moffitt sought and received approval of a single patient IND application to enable a second dose for a single patient who, upon examination of tumor obtained from a biopsy, exhibited cellular infiltration and necrosis, indicating biologic activity of the CAR-T. This amendment will permit all potential patients to receive another leukapheresis and a second dose of CAR-T, without submitting individual INDs for each patient.

Dr. Robert Wenham, Chair of the Gynecologic Oncology Department at Moffitt, and the principal investigator of the trial, stated, "In initial Phase 1 clinical trials, it is customary to begin with low, often subtherapeutic cell doses to verify safety, before increasing the dose levels. In our study, the patient approved for a second dose by the individual IND received the starting, lowest dose. While initially meeting the criteria for progression due to size of her predominate tumor, her cancer has since remained relatively stable and she has not received additional therapy since her first infusion. We are hoping a second, higher dose may improve her overall response and outcome. In general, we anticipate that higher cell doses will lead to efficacy, but for solid tumors, a second dose may be needed in a subset of patients to improve the rate and durability of responses."

"We hope to get approval from regulatory agencies shortly, to enable second doses for the appropriate patients. We are clearly enthusiastic about the progress of this trial and are looking forward to treating additional patients," stated Dr. Amit Kumar, Chairman and CEO of Anixa Biosciences.

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

Half-year report 2024

On September 30, 2024 Valerio Therapeutics reported its half-year 2024 results (Press release, Valerio Therapeutics, SEP 30, 2024, https://valeriotx.com/wp-content/uploads/2024/09/EN_-HY-financial-report-consolidated-Update-Crowe-HAF-v09262024-Formatted-signed.pdf [SID1234647056]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!


Merus Announces First Patient Dosed in LiGeR-HN1, a Phase 3 Trial Evaluating Petosemtamab in Combination with Pembrolizumab in 1L r/m HNSCC

On September 30, 2024 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported that the first patient has been dosed in the Company’s phase 3 trial evaluating the efficacy and safety of petosemtamab, a Biclonics targeting EGFR and LGR5, in combination with pembrolizumab, compared to pembrolizumab as first line (1L) therapy for patients with PD-L1+ recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC), referred to as the LiGeR-HN1 trial (Press release, Merus, SEP 30, 2024, View Source [SID1234646939]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Merus has confirmed through feedback with the U.S. Food and Drug Administration (FDA) that petosemtamab 1500 mg every two weeks is appropriate for further development in HNSCC as monotherapy, and in combination with pembrolizumab.

"Based on our strong phase 2 clinical data reported previously for petosemtamab in HNSCC both as monotherapy and in combination with pembrolizumab, I continue to be confident that petosemtamab has the opportunity to become a new standard of care across r/m HNSCC and potentially beyond," said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. "Our recently announced alignment with the FDA on phase 3 dose, and excellent execution to date has allowed us to promptly initiate our registration trials in 1L and 2/3L HNSCC."

More details of the trial can be found at clinicaltrials.gov.

About LiGeR-HN1
LiGeR-HN1, a phase 3 trial, will evaluate the safety and efficacy of petosemtamab in combination with pembrolizumab, compared to pembrolizumab in 1L PD-L1+ r/m HNSCC patients. The trial is open to adult patients eligible to receive pembrolizumab as 1L monotherapy with tumors expressing PD-L1, CPS ≥1. The primary endpoints are overall response rate as assessed by BICR based on RECIST v1.1 and overall survival. Secondary endpoints are duration of response and progression free survival. Merus plans to enroll approximately 500 patients in the trial.

About Petosemtamab
Petosemtamab, or MCLA-158, is a Biclonics low-fucose human full-length IgG1 antibody targeting the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). Petosemtamab is designed to exhibit three independent mechanisms of action including inhibition of EGFR-dependent signaling, LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity.

About Head and Neck Cancer
Head and neck squamous cell carcinoma (HNSCC) describes a group of cancers that develop in the squamous cells that line the mucosal surfaces of the mouth, throat, and larynx. These cancers begin when healthy cells change and grow in an unchecked manner, ultimately forming tumors. HNSCC is generally associated with tobacco consumption, alcohol use and/or HPV infections, depending on where they develop geographically. HNSCC is the sixth most common cancer worldwide and it is estimated that there were more than 930,000 new cases and over 465,000 deaths from HNSCC globally in 2020.1 The incidence of HNSCC continues to rise and is anticipated to increase by 30% to more than 1 million new cases annually by 2030.2 HNSCC is a serious and life-threatening disease with poor prognosis despite currently available standard of care therapies.