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REHEVA BIOSCIENCES SUCCESSFULLY COMPLETES RH324 PHASE I CLINICAL TRIAL FOR ADVANCED NON-SMALL CELL LUNG CANCER

On October 25, 2023 ReHeva Biosciences, a pioneering biopharmaceutical startup with the mission to help people live longer and healthier with cancer through naturally derived complex drugs, reported the successful completion of its Phase I Safety Trial for its novel drug, RH324 (Press release, ReHeva Biosciences, OCT 25, 2023, View Source [SID1234636344]). This achievement marks a significant milestone for the company and its mission of advancing cancer treatment options and underscores ReHeva’s commitment to revolutionizing patient care.

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The Phase I trial was conducted in collaboration with Case Comprehensive Cancer Center University Hospitals and Case Western Reserve University in Cleveland. It evaluated the safety and tolerability of escalating doses of RH324 in patients diagnosed with advanced non-small cell lung cancer (NSCLC) who have failed prior treatments.

"At ReHeva, we are driven by a steadfast belief that cancer treatment can be transformed to help patients live longer and healthier with cancer. The completion of our Phase I clinical trial represents a tremendous milestone toward realizing this vision," said Dr. Zeenia Kaul, CEO, Co-Founder, and Chief Scientific Officer of ReHeva Biosciences. "By maximizing the potential of plant-derived agents to target multiple tissues and mechanisms of action, we are advancing the narrative of cancer treatment."

Furthermore, ReHeva’s proprietary methods of drug preparation set it apart from its competitors.

Founded in 2016 by Dr. Kaul, ReHeva Biosciences draws upon more than two decades of pre-clinical research and development. The company’s commitment to scientific integrity is underscored by studies published in prestigious peer-reviewed journals, cementing its role as a leading force in oncology research.

Receiving the FDA Investigational New Drug allowance (IND) in 2018 paved the way for ReHeva’s Phase I Safety Study in advanced NSCLC patients designed to assess the safety and tolerability of RH324. This is an important step towards the goal of achieving an FDA approved indication for RH324 and its diverse and broad-spectrum potential benefits which empower the drug to effectively target various pathways implicated in cancer progression.

"Rigorous clinical trials evaluating naturally derived products created many of the treatments we use to fight cancer today," said Dr. Santosh Rao, Medical Oncologist and Director of Integrative Oncology at the University Hospitals, Cleveland.

Dr. Afshin Dowlati, Principal Investigator on ReHeva Study, Professor and Director of the Phase 1 Clinical Trials Program at University Hospitals Seidman Cancer Center added "Partnering with ReHeva Biosciences to evaluate the use of RH324 could provide patients with another treatment option for cancer with less toxicity."

Completion of the Phase 1 Safety and Tolerability trial means that future Phase 2 trials can address multiple cancer types. ReHeva Biosciences is looking forward to the RH324 clinical program.

The Power of Partnerships

One strategic partnership that is helping strengthen ReHeva Biosciences’ mission is a pioneering vertical farming company based in Hamilton, Ohio. Recognizing the need for consistent and large-scale production of the botanical raw material is central to their research, ReHeva’s collaboration with 80 Acres Farms bridges the gap between botanical drug manufacturing needs and scalable supply chain necessary for long term clinical development.

"To be successful, we need a consistent supply of high-quality botanical raw material," said Kaul. "That’s why we turned to one of the most exciting new developments in agriculture—controlled environment agriculture (CEA), which promises ingredients that are clean, dependable, and unaffected by weather and the seasons. After researching the CEA space, we recognized that 80 Acres Farms had the technology platform to deliver what we need."

Utilizing cutting-edge controlled-environment agriculture CEA technology, 80 Acres Farms cultivates crops indoors, free from pesticides, while meticulously controlling growth conditions such as light, humidity, nutrients, and water. This precision results in optimal plants for clinical use, forming a reliable supply chain for ReHeva’s groundbreaking research. This strategic partnership exemplifies ReHeva’s commitment to innovation, as both entities collaborate to pioneer next-generation agricultural tools and technologies.

"As indoor farmers, we’re invested in challenging conventional wisdom, when the data supports it," said Mike Zelkind, CEO and co-founder of 80 Acres Farms. "ReHeva is doing innovative work with plant-derived ingredients at the foundations of modern medicine. We can support that work by growing plants with pharmaceutical precision, year-round—enabling traceability, consistency, and scaling."

Partnerships play a critical role in ReHeva Biosciences work to leverage cutting-edge technology to explore the potential of botanical-based drugs in treating a range of conditions, including cancer. The company is currently exploring educational partnerships with universities including MD Anderson Cancer Center, The Ohio State University and Emory University. Through grants, ReHeva will be able to run additional clinical trials on other cancers to continue proving effectiveness and safety in treating this disease.

A testament to its groundbreaking endeavors, ReHeva Biosciences has garnered over $7 million in funding. To learn more about the transformative work at ReHeva Biosciences, visit ReHevaBiosciences.com.

About RH324

RH324 is an investigational new drug manufactured by ReHeva Biosciences. The botanical drug substance retains a "full spectrum" of the plant’s natural constituents: proteins, amino acids, various fatty acids, carbohydrates, and vitamins, minerals, and phytochemicals. RH324 is being developed in accordance with the FDA Guidance for Industry for Botanical Drug Products (Chemistry June 2004/revised Dec 2016).

Carisma to Present First Results From in vivo CAR-M Collaboration with Moderna at SITC 2023

On October 25, 2023 Carisma Therapeutics Inc. (Nasdaq: CARM) ("Carisma" or the "Company"), a clinical-stage biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported that new pre-clinical data leveraging an mRNA platform to develop in-vivo chimeric antigen receptor macrophage ("CAR-M") will be presented as a late-breaking abstract (#LBA1514) at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting held from Wednesday, November 1, to Sunday, November 5, 2023, in San Diego, California (Press release, Carisma Therapeutics, OCT 25, 2023, View Source [SID1234636343]). Two posters highlighting next-generation enhancements to Carisma’s CAR-M platform, including a custom intronic shRNA approach and data on Engineered Microenvironment Converters (EM-C), will also be presented. Additionally, Carisma will share a trial-in-progress poster overviewing its Phase 1 first-in-human (FIH) study design of its lead program, CT-0508, sharing objectives and eligibility criteria.

Carisma will participate in the virtual SITC (Free SITC Whitepaper) 2023 Annual Meeting Press Conference on Wednesday, November 1, 2023, from 12:00–1:30 pm PT.

"We are excited to present this pre-clinical data from our collaboration with Moderna for the first time," said Steven Kelly, President and Chief Executive Officer of Carisma. "Over the past year, we have leveraged the expertise of both companies to pioneer the development of in-vivo mRNA/LNP-based cell therapy. The study is exploring the potential for an off-the-shelf treatment approach to enhance therapeutic benefit for patients living with cancer."

Oral & Poster Presentations:

In vivo CAR-M: Redirecting endogenous myeloid cells with mRNA for cancer immunotherapy
Primary Author: Bindu Varghese, PhD
Presentation Type/#: Oral – 1514
Session Date/Time (PT): Friday, November 3, 2023, 11:30 am, Session 104: Late Breaking Abstract Session
CAR-Macrophages with custom intronic shRNA exhibit enhanced efficacy against solid tumors
Primary Author: Chris Sloas, PhD
Presentation Type/#: Poster – 307
Session Date/Time: Friday, November 3, 2023, 9:00 am – 7:00 pm
Engineered Microenvironment Converters (EM-C): Macrophages expressing synthetic cytokine receptors reverse immunosuppressive signals in solid tumors
Primary Author: Chris Sloas, PhD
Presentation Type/#: Poster – 389
Session Date/Time: Friday, November 3, 2023, 9:00 am – 7:00 pm
A Phase 1, First in Human (FIH) study of autologous macrophages engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants (pts) with HER2 overexpressing solid tumors
Primary Author: Kim Reiss, MD
Presentation Type/#: Poster – 635
Session Date/Time: Friday, November 3, 2023, 9:00 am – 7:00 pm
Presentation and posters will be available in the Journal for ImmunoTherapy of Cancer (JITC) supplement once published on Tuesday, October 31, 2023, at 9:00 am ET.

About CT-0508

CT-0508 is a human epidermal growth factor receptor 2 (HER2) targeted chimeric antigen receptor macrophage (CAR-M). It is being evaluated in a landmark Phase 1 multi-center clinical trial that focuses on patients with recurrent or metastatic HER2-overexpressing solid tumors whose cancers do not have approved HER2-targeted therapies or who do not respond to treatment. Carisma is selecting participants who have tumors of any anatomical origin, but with the commonality of overexpressing the HER2 receptor on the cell surface, which is the target for our CAR-M. The Phase 1 clinical trial marks the first time that engineered macrophages are being studied in humans. The trial continues to enroll patients at seven clinical sites in the U.S., including (i) Penn Medicine’s Abramson Cancer Center, (ii) the University of North Carolina Lineberger Comprehensive Cancer Center, (iii) the City of Hope National Medical Center, (iv) the MD Anderson Cancer Center, (v) the Sarah Cannon Cancer Research Institute, (vi) Oregon Health & Science University and (vii) Fred Hutchinson Cancer Center.

First Patient Dosed for MRCT Phase 3 Study on First-Line LS-SCLC of Henlius Anti-PD-1 mAb Serplulimab in Europe

On October 25, 2023 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the first patient in Europe has been dosed in the international multi-centre phase 3 clinical trial (NCT05353257) of the company’s self-developed anti-PD-1 mAb HANSIZHUANG (serplulimab) in combination with chemotherapy and concurrent radiotherapy in patients with limited-stage small cell lung cancer (LS-SCLC) in EU country Latvia (Press release, Shanghai Henlius Biotech, OCT 25, 2023, View Source [SID1234636342]). The co-leading principal investigators are Jinming Yu, an Academician of the Chinese Academy of Engineering (CAE) and the Director of Shandong Cancer Hospital, Ligang Xing, the vice director of Shandong Cancer Hospital, and Ying Cheng, the Director of Jilin Cancer Hospital. Previously, the first patients in China, the U.S., Australia and other countries and regions have been dosed.

According to GLOBOCAN 2020, lung cancer (LC) is the second most commonly diagnosed and the first mortality cancer around the world. There were 2.2 million new LC cases and 1.8 million new deaths in 2020 worldwide, and LC is still the leading cause of cancer deaths[1]. Small cell lung cancer (SCLC) accounts for 15%–20% of the total number of LC, which is featured by high malignancy, strong invasiveness, early metastasis, and rapid disease progression, with extremely poor prognosis. LC is divided into two stages, including limited stage and extensive stage, and 30%–40% patients are in limited stage at the time of diagnosis. The standard treatment regimens for LS-SCLC are surgery, chemotherapy and concurrent radiotherapy. Traditional chemotherapeutic drugs did not exhibit significant progress in patients with LS-SCLC, and most patients tend to develop drug resistance or rapid relapse[2–4]. The advent of immune checkpoint inhibitors has been proven to bring hope to patients with ES-SCLC but has not yet shown benefit in those with LS-SCLC. Recently, HANSIZHUANG was recommended by the 2022 CSCO Guidelines for Diagnosis and Treatment of Small Cell Lung Cancer for the treatment of ES-SCLC. The company is continuing to explore immuno-oncology therapy for LS-SCLC, with the goal of delivering more effective treatment for patients.

HANSIZHUANG is the first innovative mAb developed by Henlius. It has been approved by the NMPA for the treatment of MSI-H solid tumours, non-small cell lung cancer (sqNSCLC) and ES-SCLC and esophageal squamous cell carcinoma (ESCC), and has since seen benefits in 40,000 patients in China. Regarding unmet clinical needs as a core, Henlius covers the full range of first-line treatments of LC. Two global multi-centre phase 3 clinical trials regarding sqNSCLC and ES-SCLC have been conducted in China, Turkey, Poland, Georgia, and other countries and regions, with over 30% of the total enrolled subjects being White, providing more diverse cases for clinical research. ASTRUM-005, the international multi-centre, phase 3 study in patients with ES-SCLC, has been published in The Journal of the American Medical Association (JAMA), one of the top four medical journals in the world, making ASTRUM-005 became the first study published in JAMA on SCLC immunotherapy. Moreover, HANSIZHUANG has been granted orphan-drug designations for the treatment of SCLC by the United States Food and Drug Administration (FDA) and the European Commission (EC), respectively. The European Medicines Agency (EMA) has validated the application for HANSIZHUANG in combination with chemotherapy for the first-line treatment of ES-SCLC. It is worth mentioning that the first patient has been dosed in a bridging head-to-head trial in the US to comparing HANSIZHUANG to standard of care Atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC, which is expected to propel the product towards US market approval further.

In the future, the company will continue to emphasize unmet clinical needs and actively promote the combination immunotherapy of serplulimab and international commercialization process to benefit more patients around the world.

About NCT05353257

This randomised, double-blind, multi-centre, phase 3 clinical study aims to compare the efficacy and safety of serplulimab versus placebo, in combination with chemotherapy (carboplatin/cisplatin-etoposide) and concurrent radiotherapy in patients with limited-stage small cell lung cancer (LS-SCLC). Eligible patients will be randomised at a ratio of 1:1. The primary objective of this study is to evaluate the anti-tumour activity of serplulimab plus chemotherapy and concurrent radiotherapy in LS-SCLC patients. The primary endpoint is overall survival (OS). The secondary endpoints include progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) assessed by investigators per RECIST 1.1, as well as safety and immunogenicity.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first anti-PD-1 mAb for the first-line treatment of SCLC. Up to date, 4 indications are approved for marketing in China, 1 marketing application is under review in the EU, and more than 10 clinical trials are ongoing across the world.

HANSIZHUANG was launched in March 2022 and has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC). Its marketing applications of the first-line treatment for ES-SCLC are under review by the EMA. Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. It has successively obtained clinical trial approvals in China, the U.S., the EU and other countries and regions to initiate more than 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications. As of now, the company has enrolled more than 3,600 subjects in China, the U.S., Turkey, Poland, Georgia and other countries and regions, and the proportion of White is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The results of 3 pivotal trials of HANSIZHUANG were published in the Journal of the American Medical Association (JAMA), Nature Medicine and the British Journal of Cancer, respectively. Furthermore, HASIZHUANG was recommended by the CSCO Guidelines for Small Cell Lung Cancer, the CSCO Guidelines for Non-Small Cell Lung Cancer, the CSCO Guidelines for Esophageal Cancer, the CSCO Guidelines for Colorectal Cancer, the CSCO Clinical Practice Guidelines on Immune Checkpoint Inhibitor, the China Guidelines for Radiotherapy of Esophageal Cancer, and other definitive guides, providing valuable references for clinical diagnosis and treatment of tumours. On the other hand, serplulimab was granted orphan drug designations by the U.S. FDA and the EC for the treatment of SCLC, and its bridging head-to-head trial in the United States to compare HANSIZHUANG to standard of care atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC is well under way.

Qilu Pharmaceutical announces the latest results from its clinical study on QL1706, in combination with chemotherapy, as a first-line treatment for recurrent or metastatic cervical cancer

On October 25, 2023 Qilu Pharmaceutical reported the latest findings from a multicenter, single-arm Phase II clinical trial at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Congress 2023 (Press release, Qilu Pharmaceutical, OCT 25, 2023, View Source [SID1234636341]). This trial studied the use of QL1706 (iparomlimab and tuvonralimab) in combination with chemotherapy, with or without bevacizumab, as a first-line treatment of recurrent or metastatic cervical cancer (r/mCC). Professor Danbo Wang from Liaoning Cancer Hospital & Institute reported these findings.

The study results indicated that using QL1706 in combination with chemotherapy, with or without bevacizumab, as a first-line treatment for r/mCC showed a promising objective response rate (ORR) and survival benefits. Moreover, the treatment exhibited a manageable safety profile without any new safety signals observed, making it a potential new first-line treatment option for r/mCC patients.

I. Research Background

Currently, the preferred standard first-line treatment for r/mCC patients is cisplatin or carboplatin and paclitaxel plus bevacizumab, and efficacy and safety of the treatment also need to be considered. For r/mCC patients with positive PD-L1 expression, the PD-1 inhibitor pembrolizumab, administered with chemotherapy and with or without bevacizumab, is recommended as the standard first-line treatment. Immunotherapy combined with chemotherapy has now become the standard care for r/mCC [1-2]. The latest results from the KEYNOTE-826 study showed that the median progression-free survival (PFS) of PD-L1-positive (CPS ≥1) r/mCC treated with immunotherapy-chemotherapy-pembrolizumab, with or without bevacizumab, increased from 8.2 months to 10.4 months. Furthermore, the median overall survival (OS) extended from 16.5 months to 28.6 months. While the PD-1 inhibitor combined with chemotherapy have significantly improved patient survival compared to chemotherapy alone, the survival benefits for patients remain limited, indicating an unmet clinical need [3-4].

II. Study Design

This study enrolled r/mCC patients who had not undergone systemic therapy. These patients were treated with either QL1706-chemotherapy (Cohort 1) or QL1706-chemotherapy-bevacizumab (Cohort 2) until disease progression, the occurrence of intolerable toxicity or the patient’s withdrawal of informed consent. The primary endpoint of the study was safety. Secondary endpoints included ORR, duration of response (DOR), disease control rate (DCR), PFS, which were assessed by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and OS. The study design is illustrated in Figure 1.

III. Study Results

A total of 60 patients were enrolled to cohort 1 and cohort 2, 30 patients in each cohort. Patients in cohort 1 were treated with QL1706 monoclonal antibody combined with either cisplatin or carboplatin and paclitaxel. Patients in Cohort 2 received the same regimen as the first but with addition of bevacizumab. The mean age of the patients was 52.0 years, with 58.3% having an ECOG Performance Status of 1. Squamous cell carcinoma was the pathological type in 78.3% of the patients, while recurrent CC was found in 86.7%.

As of April 24, 2023, the median follow-up was 14 months. Out of 58 patients who received at least one post-baseline efficacy evaluation, ORR was 81.0% (95% CI, 68.6-90.1). Among these patients, eight achieved complete response (CR) and 39 achieved partial response (PR). The DCR was 98.3% (95% CI, 90.8-100.0). The median PFS reached 14.3 months (95% CI, 9.2 months to not estimable), while the median OS had not yet been reached. In cohort 2, with combination treatment of bevacizumab, the median PFS was 16.4 months. (Figure 2)

In terms of safety, treatment-related adverse events (TRAEs) were observed in all patients, with a 71.7% incidence of grade 3 or higher adverse events. The most common TRAEs included white blood cell count decreased (71.3%), neutrophil count decreased (68.3%), and anemia (43.3%). The incidence of treatment-related serious adverse events was 30%; the occurrence of immune-related adverse events (irAEs) was 13.3%; TRAEs leading to discontinuation of therapy occurred in 26.7% of patients; and the incidence of treatment-related deaths was 1.7%, possibly related to bevacizumab (Figure 3).

IV. Summary

The results of this study demonstrated that the first-line treatment of r/mCC with QL1706 combined with chemotherapy, with or without bevacizumab, showed promising efficacy and favorable safety, regardless of level of PD-L1 expression.

Based on these findings, a Phase III clinical trial of QL1706 in combination with chemotherapy, with or without bevacizumab, for the treatment of persistent, recurrent, or metastatic CC is currently ongoing. Furthermore, the New Drug Application (NDA) for the treatment of r/mCC patients who have failed at least one first-line standard platinum-based therapy with QL1706 was accepted by the Center for Drug Evaluation (CDE) in August of this year.

References:

1. Guidelines Working Committee of the Chinese Society of Clinical Oncology. Guidelines for the Diagnosis and Treatment of Cervical Cancer [M]. 2023. Beijing: People’s Medical Publishing House, 2023:70.

2. Tewari KS, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med. 2014 Feb 20;370(8):734-43. doi: 10.1056/NEJMoa1309748. Erratum in: N Engl J Med. 2017 17;377(7):702.

3. Colombo N, et al. Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. N Engl J Med. 2021 11;385(20):1856-1867.

4. J Clin Oncol 41, 2023 (suppl 16; abstr 5500).

ESMO 2023 Presentation

On October 25, 2023 Moderna presented its corporate presentation (Press release, Moderna Therapeutics, OCT 25, 2023, View Source [SID1234636340]).