On January 18, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported that new data on its personalized and tumor-informed molecular residual disease (MRD) test, Signatera, will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s 2024 Gastrointestinal Cancers Symposium (ASCO GI), taking place January 18 – 20, 2024 in San Francisco, California (Press release, Natera, JAN 18, 2024, View Source [SID1234639345]).

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Natera and its collaborators will present 11 abstracts that feature new Signatera data across various GI indications, including two oral presentations. An updated analysis from the previously published GALAXY study, the observational arm of the prospective CIRCULATE-Japan trial, will be presented in an oral presentation at the symposium and is also featured in ASCO (Free ASCO Whitepaper) GI’s press program. GALAXY is one of the largest and most comprehensive prospective studies of MRD testing in resectable colorectal cancer (CRC).

Additionally, the first read-out from the Natera-sponsored BESPOKE CRC study will be presented in a rapid oral presentation. BESPOKE CRC is the first large, prospective, US-based study in resectable CRC, with over 130 participating sites.

Highlights from the abstracts selected for oral presentation include:

Abstract ID: 6 | Oral Abstract Session C | CRC | Presenter: Hiroki Yukami, MD
Circulating tumor DNA (ctDNA) dynamics in CRC patients (pts) with MRD: Updated analysis from GALAXY study in CIRCULATE-JAPAN

This latest analysis from GALAXY included close to 3,000 stage I-IV CRC patients. Key findings include:

ctDNA dynamics at the six-month time point post-surgery showed that patients who remained ctDNA-positive were >6 times more likely to recur compared to those who cleared their ctDNA.
ctDNA-positive patients with sustained clearance in subsequent time points as a result of adjuvant chemotherapy (ACT) had remarkably better outcomes compared to those with transient ctDNA clearance (24-month DFS rate; 90.1% vs 2.3%) or no clearance (24-month DFS rate; 90.1% vs 2%).
In ctDNA-positive patients treated with ACT, a >50% decrease in ctDNA MTM/mL levels at six months, including those with complete clearances, was associated with better DFS than a <50% decrease or increase (24-month DFS rate; 51.1% vs 29%).
Abstract ID: 9 | Rapid Oral Abstract Session C | CRC | Presenter: Pashtoon Kasi, MD, MS
ctDNA for informing adjuvant chemotherapy (ACT) in stage II/III CRC: Interim analysis of BESPOKE CRC study

This analysis included 689 patients with stage II/III resectable CRC. Key findings include:

Within the ctDNA-positive cohort, patients receiving ACT had significantly longer DFS compared to those in the observation group (24-month DFS rate; 42.4% vs 12.5%). No benefit of ACT was observed in ctDNA-negative patients.
ctDNA monitoring allowed for oligometastases-directed therapy in 40% of patients who recurred.
A separate poster on the BESPOKE CRC study (abstract ID: 54) found that in 400+ patients surveyed, ≥92% valued the information received from their Signatera results or would use Signatera to guide their clinical care. In addition, 73% reported that Signatera results reduced anxiety about cancer recurrence.
"These latest findings from the landmark CIRCULATE trial underscore Signatera’s ability to identify patients who may be more likely to benefit from adjuvant chemotherapy, showing the value of personalized MRD testing to guide treatment decisions in CRC and potentially spare patients from unnecessary toxicity," said Hiroki Yukami, MD, from the Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University, and lead study author of the GALAXY study. "We are encouraged by the widespread attention and recognition this presentation has received from the oncology community, and are optimistic that the GALAXY study, along with the ALTAIR escalation and VEGA de-escalation arms of CIRCULATE, will fundamentally change the way CRC is treated."

"We are pleased to share new data from the Japanese-based GALAXY and US-based BESPOKE CRC studies, which further demonstrate the prognostic and predictive power of longitudinal testing with Signatera in resectable colorectal cancer," said Minetta C. Liu, MD, chief medical officer of oncology at Natera. "These two prospective clinical trials provide strong evidence supporting the clinical utility of Signatera to inform adjuvant chemotherapy decisions and facilitate surveillance for cancer recurrence."

Below are the additional Natera poster presentations at ASCO (Free ASCO Whitepaper) GI:

Abstract ID: 54 | CRC | Presenter: Pashtoon Kasi, MD, MS
Patient-reported outcomes from the BESPOKE CRC study
Abstract ID: 27 | CRC | Presenter: Giulia Maddalena, MD
INTERCEPT Program of ctDNA Testing for MRD in CRC: Results from a Prospective Clinical Cohort
Abstract ID: 183 | CRC | Presenter: Hidekazu Oyoshi
Prediction of postoperative recurrence by integrating preoperative ctDNA levels and tumor metastasis volume in pts with CRC with resectable lung or liver metastasis
Abstract ID: 528 | Bile Duct Cancer | Presenter: Woo Jin Choi, MD, PhD
The role of pre-operative ctDNA in resectable intrahepatic cholangiocarcinoma
Abstract ID: 212 | Rectal Cancer | Presenter: Sakti Chakrabarti, MD
Prognostic value of ctDNA testing in rectal cancer pts after neoadjuvant therapy (NAT) and surgery
Abstract ID: 23 | CRC | Presenter: Masaaki Miyo, MD, PhD
Association of ctDNA MRD detection with lymph node metastasis after local excision of pathological T1 CRC: First results from DENEB, a CIRCULATE-Japan GALAXY substudy
Abstract ID: 196 | CRC | Presenter: Andrew Pellatt, MD
Redefining The Prognostic Significance of RAS and BRAF V600E Mutations on Disease Free Survival in CRC Pts in the Era of ct-DNA Defined MRD: Results from the MD Anderson INTERCEPT Program
Abstract ID: 695 | Pancreatic Cancer | Presenter: Ujwal Yanala, MD
Utility of ctDNA for the detection of MRD after curative-intent therapy for pts with localized pancreatic adenocarcinoma (PDAC): A single institution series and meta-analysis
Abstract ID: 214 | CRC | Presenter: Nikolas Naleid, MD
Surveillance of Resected Metastatic Colorectal Cancer Utilizing Circulating DNA
About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer (stage IIb and higher) and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 50 peer-reviewed papers.

On January 18, 2024 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs reported the publication of clinical data from studies of CPP-1X (also known as α-Difluoromethylornithine (DFMO) or Eflornithine) in neuroblastoma (Press release, Panbela Therapeutics, JAN 18, 2024, View Source [SID1234639332]). According to Hogarty et al, children with relapsed refractory neuroblastoma have dismal outcomes and new therapeutic options are needed. Data published in the British Journal of Cancer investigated the tolerability and activity of depleting polyamines by high dose CPP-1X and celecoxib in combination with standard of care chemotherapy in heavily pretreated neuroblastoma patients. Results showed that DFMO treatment was well tolerated, and the median time-to-progression was 19.8 months. The work reflects the Company’s previous collaboration with New Advances in Neuroblastoma Therapy Consortium (NANT) (View Source). A link to the publication can be found here: View Source

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From the Phase 1 dose range finding study of CPP-1X in heavily pretreated neuroblastoma patients, CPP-1X was well tolerated. The best overall response included 2 partial responses (PR), 4 minor responses (MR), 10 Stable disease (SD), 7 progressive disease (PD) and 1 unevaluable. All patients with an overall response of PR or MR sustained this response until stopping or completing protocol therapy. The overall objective response rate (CR+PR) was 9% and rate of any response (CR+PR+MR) was 26%. At 2 years, PFS (progression free survival) for the entire cohort was 29.5%. Notably, three patients completed protocol therapy and remain without disease progression or event at >4 years from treatment end in the absence of additional therapy.

These results build upon the recent FDA approval of CPP-1X or DFMO to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB) who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy. Results from these studies suggest that CPP-1X is a safe, oral treatment option that may improve response rates in heavily pretreated relapsed refractory neuroblastoma patients and are the basis for the ongoing ANBL-1821 Phase 2 trial.

"We are excited about the publication of these Phase 1 trial results in light of the recent DFMO FDA approval for patients in maintenance therapy. From this dose escalation study, our collaborators were able to demonstrate high dose DFMO is well tolerated and demonstrated activity in patients with heavily pretreated neuroblastoma," said Elizabeth Bruckheimer, PhD, Vice President & Chief Scientific Officer of Panbela. "Moreover, three patients remain alive over four years from treatment end without any additional therapy which suggests that high dose DFMO treatment in combination with chemotherapy may be a potential treatment option for this high unmet need population."

"Overall, these results in addition to the recent approval of DFMO as a maintenance therapy, suggests a role for polyamine inhibition therapy for neuroblastoma that may impact other cancer types such as prostate cancer. We are excited by these results and the potential role for CPP-1X in the clinical management of neuroblastoma and cancer as a whole." said Dr. Bruckheimer. "These studies were the basis for the ongoing Children’s Oncology Group Phase II trial in relapsed refractory neuroblastoma to support the goal of developing effective novel therapies for patients with unmet medical needs."

First author Michael Hogarty, MD, Professor of Pediatrics at the University of Pennsylvania, and Children’s Hospital of Philadelphia said, "The results from the Phase 1 study have built upon the preclinical work performed in my laboratory demonstrating a role of deep polyamine depletion as a potential therapeutic target for relapsed or refractory neuroblastoma. By understanding the underlying biology and role of MYC signaling and the polyamine pathway in neuroblastoma, we are able to show the potential impact of high-dose DFMO in neuroblastoma."

On January 18, 2024 Novocure (NASDAQ: NVCR) reported that its Premarket Approval (PMA) application seeking approval for the use of Tumor Treating Fields (TTFields) therapy together with standard systemic therapies for the treatment of non-small cell lung cancer (NSCLC), following progression on or after platinum-based therapy, has been accepted for filing by the U.S. Food and Drug Administration (FDA) (Press release, NovoCure, JAN 18, 2024, View Source [SID1234639346]).

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"We are thrilled to announce the FDA has accepted our PMA application for review of the LUNAR data in NSCLC," said Asaf Danziger, Novocure’s Chief Executive Officer. "This significant milestone brings us one step closer to treating patients seeking treatment for NSCLC, post-platinum, for which very few effective non-toxic options exist today. I would like to thank our investigators and patients, as well as our Novocure colleagues, for their dedication in pursuit of bringing our novel therapy to thousands of patients in need."

The PMA application for LUNAR was submitted with a filing date of December 15, 2023, and is now under substantive review by the FDA. Novocure expects to receive a regulatory decision from FDA in second half 2024.

About LUNAR

LUNAR tested the safety and effectiveness of TTFields therapy when used together with either an immune checkpoint inhibitor (ICI) or docetaxel for the treatment of patients diagnosed with metastatic NSCLC following progression on or after the use of platinum-based therapy. Patients randomized to receive TTFields therapy together with standard therapies (n=137) demonstrated median overall survival (OS) of 13.2 months compared to 9.9 months in patients treated with standard therapies alone (n=139). Patients randomized to receive TTFields therapy and physician’s choice ICI (n=66) demonstrated a median OS of 18.5 months versus a median OS of 10.8 months in patients treated with an ICI alone (n=68; HR=0.63; P=0.03). Patients randomized to receive TTFields therapy and docetaxel (n=71) had a positive survival trend with a median OS of 11.1 months vs 8.7 months in patients treated with docetaxel alone (n=71). TTFields therapy was well-tolerated with no added systemic toxicities and few grade 3 (no grade 4 or 5) device-related adverse events.

About NSCLC

Lung cancer is the most common cause of cancer-related death worldwide, and NSCLC accounts for approximately 85% of all lung cancers. It is estimated that approximately 193,000 patients are diagnosed with NSCLC each year in the U.S. Physicians use different combinations of surgery, radiation and pharmacological therapies to treat NSCLC, depending on the stage of the disease. Surgery, which may be curative in a subset of patients, is usually used in early stages of the disease. Since 1991, radiation with a combination of platinum-based chemotherapy drugs has been the first-line standard of care for locally advanced or metastatic NSCLC. Certain immune checkpoint inhibitors have been approved for the first-line treatment of NSCLC and the standard of care in this setting appears to be evolving rapidly. The standard of care for second-line treatment is also evolving and may include platinum-based chemotherapy for patients who received immune checkpoint inhibitors as their first-line regimen, docetaxel, immune checkpoint inhibitors or pemetrexed.

On January 18, 2024 Portage Biotech presented its corporate presentation (Presentation, Portage Biotech, JAN 18, 2024, View Source [SID1234639333]).

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On January 18, 2024 Alaya.bio, a biotechnology company developing a novel polymeric delivery platform towards in situ cell therapies, reported a collaboration with CAR-T pioneer Michel Sadelain, MD, PhD, Stephen and Barbara Friedman Chair and Director, Center for Cell Engineering at the Memorial Sloan Kettering Cancer Center (MSK) in New York City (Press release, Memorial Sloan-Kettering Cancer Center, JAN 18, 2024, https://www.businesswire.com/news/home/20240118114142/en/Alaya.bio-announces-significant-collaboration-with-leading-global-cancer-center-to-advance-in-situ-CAR-T-Therapy [SID1234639347]). The collaboration will advance research into in situ CAR-T cell therapies and evaluate their potential to deliver faster, more effective, and cost-efficient treatments for patients.

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Dr. Sadelain will join Alaya.bio as a scientific co-founder. The collaboration with the Sadelain lab includes a license agreement and a sponsored research agreement. Over the coming two years the Sadelain lab will lead activities to advance Alaya.bio’s polymeric delivery platform into the clinic in a chosen hematological malignancy.

Alaya.bio is developing a unique in situ CAR solution. While offering tremendous promise, traditional ex vivo CAR therapies suffer from significant complexity, long manufacturing cycles and high cost that still represent major hurdles to their widespread use. Alaya.bio’s proprietary polymeric in situ delivery platform is configured to meet the stringent demands of CAR therapy: its targeting agent, grafted onto the polymeric shell, precisely directs nanoparticles to T-cells, ensuring efficient and safe delivery of the therapeutic cargo. This innovative approach guarantees stable expression of the CAR transgene and preserves transduced T-cells from exhaustion, two crucial features for long-term clinical benefit.

Cécile BAUCHE, Ph.D., co-founder and CSO at Alaya.bio, emphasizes the privilege to collaborate with a world-leading institute, such as MSK and a CAR-T pioneer like Dr. Sadelain: "It is an immense pride that MSK and Dr. Sadelain decided to join forces to develop Alaya.bio’s in situ CAR-T platform."

"The ingenuity of Alaya.bio’s targeting polymeric nanoparticles has the potential to simplify and refine the development, manufacturing, and administration of CAR-T cell therapies in ways that expand applications and make them more accessible to patients," said Dr. Sadelain. "I am excited to leverage this technology and support its advancement on the frontiers of cell and gene therapy for patients."

Renaud Vaillant, co-founder and CEO at Alaya.bio, underscores, "Our collaboration with Dr. Sadelain will accelerate the validation of our novel polymeric delivery platform. In parallel, we will take advantage of our platform versatility, through partnering opportunities, to extend its use to adjacent therapeutic areas, while leveraging other innovative payloads like mRNA and gene editing technologies."

Renaud Vaillant will present information about this new collaboration at the MSK Life Sciences Innovation Showcase on January 26, 2024, in New York City.