On April 12, 2023 The National Cancer Institute, part of the National Institutes of Health (NIH), reported it has helped launch a phase 3 randomized clinical trial (NCT05633602) of a two-drug combination to treat patients with advanced non-small cell lung cancer (NSCLC) (Press release, US NCI, APR 12, 2023, View Source [SID1234630000]). Called the Pragmatica-Lung Study (or S2302), this is one of the first NCI-supported clinical trials to use a trial design that removes many of the barriers that prevent people from joining clinical trials. This "pragmatic" approach aims to increase accessibility to clinical trials.

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The study is part of a broader effort by NIH and the U.S. Food and Drug Administration (FDA) to modernize clinical trials. Pragmatic clinical trials have fewer and simpler eligibility criteria than conventional trials, while still ensuring the safety of patients. The hope is that this type of simplified trial can be less burdensome to patients and investigators, accrue study participants faster, be more representative of the real-world patient population, and serve as a model for future cancer clinical trials.

"This study is designed to eliminate potential barriers to enrollment and provides a model for increasing diversity and enrollment in clinical trials," said Monica M. Bertagnolli, M.D., director of NCI. "Pragmatica-Lung, with its critical public and private partnerships, reflects the innovative approaches NCI is taking to achieve the Cancer Moonshot℠ goals, including reducing the cancer death rate by 50% within the next 25 years."

The trial will evaluate whether a combination of two FDA-approved medications, ramucirumab (Cyramza, manufactured by Eli Lilly and Company) and pembrolizumab (Keytruda, manufactured by Merck), improves overall survival (how long people live) over standard treatment in people with advanced NSCLC whose disease has progressed after previous treatment with immunotherapy and chemotherapy.

"These trials will make it easier for physicians who do not work in big academic medical centers to enroll their patients, resulting in participation by more diverse populations," said James H. Doroshow, M.D., director of NCI’s Division of Cancer Treatment and Diagnosis. "Making trials more accessible, while upholding rigorous scientific and safety standards, means that more health care practitioners and patients will have an opportunity to participate."

The trial will enroll up to 700 participants from around the United States. Adults ages 18 and older with stage 4 or recurrent NSCLC who were previously treated with immune checkpoint inhibitors (a type of immunotherapy) and chemotherapy will be randomly assigned to receive either ramucirumab plus pembrolizumab or standard treatment. The study will look primarily at how long patients in the two groups live and is expected to complete enrollment by the end of 2025.

Pragmatica-Lung seeks to confirm the encouraging results of a randomized phase 2 clinical trial (S1800A)Exit Disclaimer conducted as part of the Lung Cancer Master Protocol (Lung-MAP), the first lung cancer precision medicine trial supported by NCI. That trial involved 136 patients with advanced NSCLC who had been previously treated with chemotherapy and immunotherapy, and it found evidence that the combination of ramucirumab plus pembrolizumab extended survival compared with standard treatment. Ramucirumab is a targeted drug that works by preventing new blood vessels from growing, and pembrolizumab is an immunotherapy that helps the body’s immune system attack the cancer.

The pragmatic approach is most appropriate for trials in which the drugs being studied have already been approved and their side effects are well understood, Dr. Doroshow said.

NCI collaborators for the Pragmatica-Lung Study include the SWOG Cancer Research Network, which designed and is leading the trial in collaboration with the Alliance for Clinical Trials in Oncology.

The study will be conducted with the participation of SWOG, Alliance, and two other U.S. NCI National Clinical Trials Network (NCTN) groups that focus on cancer in adults, ECOG-ACRIN Cancer Research Group and NRG Oncology. Together, these four NCTN groups represent more than 1,600 cancer treatment institutions in the United States, and doctors from any of these sites can enroll patients on the trial.

On April 12, 2023 Microbiotica, a leader in discovering and developing microbiome-based therapeutics and biomarkers, reported that it has entered into a clinical trial collaboration with MSD (Merck & Co., Inc., Rahway, NJ, USA) (Press release, Microbiotica, APR 12, 2023, View Source [SID1234629999]).

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Under the terms of the agreement, Microbiotica will conduct a phase 1b clinical trial to evaluate the safety and tolerability, and initial signs of clinical activity of its live biotherapeutic product, MB097, in combination with KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy, in melanoma patients with primary resistance to an anti-PD-1-containing immunotherapy. Microbiotica will be the study sponsor and MSD will supply KEYTRUDA.

MB097 is an orally administered live biotherapeutic product consisting of a defined consortium of nine bacterial strains designed to enhance the efficacy of immune checkpoint inhibitors (ICIs) such as KEYTRUDA.

The bacterial strains in MB097 were identified by analysing the microbiome of patients in multiple studies of ICIs in melanoma. Microbiotica’s discovery platform facilitates precise, strain-level identification of bacterial signatures associated with clinical response. Moreover, MB097 displayed potent anti-tumour efficacy in combination with ICIs in in vivo tumour models and demonstrated multiple immuno-stimulatory mechanisms in primary human immune cell assays including Cytotoxic T Lymphocyte activation and tumour cell killing in vitro.

Tim Sharpington, CEO of Microbiotica, said: "We are delighted to be working with MSD, a world leader in immuno-oncology. The treatment of patients with advanced melanoma has been revolutionised by ICIs such as KEYTRUDA and there is an opportunity to increase the number of patients who can benefit from these treatments. There is growing evidence that the gut microbiome plays a critical role in determining a patient’s response to ICIs and we believe that MB097, in combination with KEYTRUDA, has the potential to enhance the benefit for patients with advanced melanoma and other difficult-to-treat cancers."

(KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.)

On April 12, 2023 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported that enrollment has been completed in Part A of the Phase 2 DeFianCe study evaluating DKN-01, Leap’s anti-Dickkopf-1 (DKK1) antibody, in combination with standard of care bevacizumab and chemotherapy as a second-line treatment for patients with advanced colorectal cancer (CRC) (Press release, Leap Therapeutics, APR 12, 2023, View Source [SID1234629998]).

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"The completion of enrollment of Part A of the DeFianCe study is an important milestone for the DKN-01 colorectal cancer development program," said Cynthia Sirard, M.D., Chief Medical Officer of Leap. "We were very pleased with the enthusiasm of our investigators and patients for participating in Part A, which reflects the unmet medical need of second-line CRC patients and their conviction in the DKN-01 preclinical data and mechanism of action. We look forward to initial data from the study in mid-2023."

The DeFianCe study (NCT05480306) is a Phase 2, randomized, open-label, multicenter study of DKN-01 in combination with standard of care bevacizumab and chemotherapy in patients with advanced CRC who have received one prior systemic therapy for advanced disease. The study began with an initial Part A cohort that has enrolled 33 patients and is designed to expand into a 130-patient Part B randomized controlled trial. The primary objective is progression free survival. Secondary objectives include overall response rate, duration of response, and overall survival.

About DKN-01

DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 has an important role in mediating an immune suppressive tumor microenvironment and in promoting tumor proliferation, metastasis, and angiogenesis. By removing free DKK1 from the tumor microenvironment, DKN-01 activates NK cells, reduces immune suppressor cells, and stimulates an immune-mediated anti-tumor response. In addition to the DeFianCe study, DKN-01 is being evaluated in the randomized controlled DisTinGuish study in first-line gastric cancer patients in combination with tislelizumab and chemotherapy and in an investigator-sponsored trial in advanced endometrial cancer patients in combination with pembrolizumab.

About Colorectal Cancer

Colorectal cancer (CRC) includes colon cancer, rectal cancer, and anal cancer. When the symptoms of CRC appear, such as rectal bleeding, anemia, or abdominal pain, most patients are already in the advanced stage where cancers are aggressive, malignant, and metastatic. CRC is the third most frequent cancer globally and the second leading cause of cancer-related death. According to the WHO, there were nearly 2,000,000 new cases of CRC in 2020, with nearly 1,000,000 deaths. It is estimated that there will be approximately 150,000 cases of CRC in the US in 2023, resulting in more than 50,000 deaths.

On April 12, 2023 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported that the first patient has been dosed in a Phase 1/2 clinical study evaluating KVA12123 alone and in combination with the immune checkpoint inhibitor pembrolizumab in patients with advanced solid tumors (Press release, Kineta, APR 12, 2023, View Source;utm_medium=rss&utm_campaign=kineta-announces-first-patient-dosed-in-phase-1-2-clinical-study-of-kva12123-for-advanced-solid-tumors [SID1234629994]). KVA12123 is a novel VISTA blocking immunotherapy designed to address immunosuppression in the tumor microenvironment (TME). Patients are currently being enrolled for this study across multiple clinical sites in the United States. Initial readout of Phase 1 data is expected by the end of 2023.

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There is a strong clinical rationale for targeting VISTA with an antibody immunotherapy. VISTA is up-regulated after checkpoint inhibitor therapy and the protein is highly expressed in colorectal, renal cell carcinoma, head and neck, ovarian, and non-small cell lung cancers. These factors correlate with poor outcomes in cancer patients. KVA12123 is a fully human engineered IgG1 monoclonal antibody that was designed to bind to VISTA through a unique epitope at both physiologic and acidic pH levels. KVA12123 has demonstrated compelling activity in a range of preclinical cancer models as monotherapy and in combination with checkpoint inhibitor therapy. It was also observed to be well-tolerated in preclinical toxicology studies.

"New cancer immunotherapies continue to transform the standard of care and have significantly improved overall survival for patients with cancer. Despite the introduction of these novel therapies, most patients still progress following treatment leaving an urgent medical need for new treatments," said Evan Yu, M.D., Section Head for Cancer Medicine, Clinical Research Division at the Fred Hutchinson Cancer Center and Principal Investigator of the study. "We are excited to kick off this Phase 1 trial to evaluate Kineta’s VISTA blocking immunotherapy as a potential approach to alleviate immunosuppression and promote antitumor immune responses in the tumor microenvironment."

The Phase 1/2 clinical study (NCT05708950) is designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and tumor response of KVA12123 alone and in combination with pembrolizumab in patients with advanced solid tumors. The study will be conducted in 4 parts. The Phase 1 study (Parts A and B) will focus on dose escalation of KVA12123 as a single-agent and in combination with pembrolizumab and will transition into a Phase 2 study (Parts C and D) that will focus on dose expansion. Additionally, Parts A and B will be used to determine a recommended Phase 2 dose (RP2D) for Parts C and D.

"KVA12123 represents a potentially promising new treatment option for a number of difficult-to-treat cancers," said Shawn Iadonato, Ph.D., Chief Executive Officer of Kineta. "Initiation of this first-in-human trial of KVA12123 marks an important milestone for Kineta and brings us one step closer to delivering a next-generation immunotherapy that addresses cancer immune resistance."

On April 12, 2023 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported that John A. Scarlett, M.D., Geron’s Chairman and Chief Executive Officer, is scheduled to participate in fireside chats at following investor conferences (Press release, Geron, APR 12, 2023, View Source [SID1234629993]):

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22nd Annual Needham Virtual Healthcare Conference
Thursday, April 20 at 10:15 a.m. ET

Stifel 2023 Virtual Targeted Oncology Days
Tuesday, April 25 at 2:00 p.m. ET

A webcast of each fireside chat and corporate presentation will be available through the Investor Relations section of Geron’s website under Events. Following each scheduled conference event, the related webcast will be archived and available for replay for a period of 30 days.