On June 3, 2024 TriSalus Life Sciences, Inc. (Nasdaq: TLSI), an oncology company integrating its novel Pressure Enabled Drug Delivery (PEDD) technology with immunotherapy to transform treatment for patients with liver and pancreatic tumors, reported that data from its Phase 1b PERIO-02 clinical trial was presented in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Annual Meeting, taking place May 31-June 4, 2024, in Chicago, Illinois (Press release, TriSalus Life Sciences, JUN 3, 2024, View Source [SID1234644067]).

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The PEDD approach is a proprietary delivery mechanism developed by TriSalus that aims to overcome challenges of the tumor microenvironment (TME) by modulating pressure and flow to enhance local drug concentrations in tumors by improving intravascular therapeutic delivery. The PERIO-02 clinical trial is the hepatic arterial infusion (HAI) of nelitolimod with the PEDD method to enhance tumor response in combination with intravenous checkpoint inhibition in adults with Hepatocellular Carcinoma (HCC) or Intrahepatic Cholangiocarcinoma (ICC).

"The PEDD approach represents a promising new delivery method that addresses the limitations of intravenous infusions or needle injections to deliver therapeutics such as nelitolimod to immune cells throughout and surrounding the tumor microenvironment," said Mary Szela, Chief Executive Officer and President of TriSalus. "The findings from the PERIO-02 clinical trial demonstrate the potential of the PEDD method to treat patients with HCC and ICC and provide initial clinical validation that HAI of nelitolimod is well tolerated with encouraging immunologic activity. We look forward to presenting these data and engaging with the medical community at ASCO (Free ASCO Whitepaper)."

Key Findings from the Phase 1b PERIO-02 Clinical Trial

At the 4 mg dose in cohort C, three of three patients had disease control as best on-treatment response, with one complete response (CR) in the liver (5L ICC), one partial response (PR) (-31%), and one stable disease (SD). For patient 101-017, investigators noted decreases in the target liver lesion (31.3 to 17.5 mm), non-target liver lesion, and extra-hepatic lymph nodes on days 53 and 84 with CR of target liver lesions and stability of extra-hepatic nodal lesions reported on day 154.
Median progression-free survival (PFS) in the Cohort C 4 mg dose level is > 120 days. Median overall survival (OS) for this group has not been reached (range 120-170 days).
Immune effects of nelitolimod included increases in liver tumor CD4 and CD8 T cells and an increase in the CD8 T cell:MDSC ratio.
Gene expression changes revealed increased Th1 programming as well as increased expression of granzyme A, IFNγ, and CXCL10 in both liver tumor and surrounding normal liver.
Changes among plasma marker levels included increased IL-2R and CXCL10 expression, with decreased IL-17A, IDO, and NT5E (CD73).
"The PERIO-02 data presented by Dr. Sunyoung Lee from the University of Texas MD Anderson Cancer Center illustrate that SD-101 is well tolerated when given by the PEDD method in patients who often have underlying liver disease, in association with encouraging biologic activity. The effects noted in PERIO-02 patients, including liver myeloid derived suppressor cell depletion and broad tumor microenvironment immune stimulation, are consistent with previously reported data in metastatic liver tumors (PERIO-01) and locally advanced pancreatic adenocarcinoma (PERIO-03)," said Steven C. Katz, MD, FACS, Chief Medical Officer at TriSalus.

PERIO-02 is an open-label phase 1 trial of nelitolimod given by the PEDD method in HCC and ICC. The study consists of dose-escalation cohorts of nelitolimod alone (Cohort A), with IV pembrolizumab (Cohort B), or IV nivolumab + ipilimumab (Cohort C). Nelitolimod is delivered over two cycles, with three weekly doses per cycle. Blood, liver tumor, and normal liver biopsies are collected for correlative studies.

Details about the presentation can be found below and on the ASCO (Free ASCO Whitepaper) website. Additionally, a copy of the poster will be available on the publications page of the TriSalus website.

Title: PERIO-02: Phase 1b Pressure Enabled Regional Immuno-oncology Trial of nelitolimod (SD-101), a Class C TLR9 agonist, delivered via hepatic artery infusion +/- checkpoint inhibition in intrahepatic cholangiocarcinoma and hepatocellular carcinoma
Presenter: Dr. Sunyoung Lee, associate professor of Gastrointestinal (GI) Medical Oncology at the University of Texas MD Anderson Cancer Center
Date: Saturday, June 1, 2024
Session Time: 9:00-12:00 p.m. CT/10:00-1:00 p.m. ET
Poster Session: Developmental Therapeutics—Immunotherapy
Abstract: 2622

On June 3, 2024 Calidi Biotherapeutics Inc. (NYSE American: CLDI) ("Calidi"), a clinical-stage biotechnology company developing a new generation of targeted immunotherapies, reported the presentation of three abstracts in a poster session during the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Calidi Biotherapeutics, JUN 3, 2024, View Source [SID1234644066]). These posters, presented on June 1, 2024, include an update from the City of Hope-led Phase 1 study of Calidi’s CLD-101 program, and preclinical data surrounding Calidi’s RTNova (CLD-400) and CLD-201 platforms.

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"We are thrilled by the opportunity to present at ASCO (Free ASCO Whitepaper) and showcase the progress we have made across our various programs. Calidi’s cutting edge approach to antitumor virotherapy is evident through the entirety of our pipeline, and these data updates are reflective of the tireless work from our scientific team and collaborators" said Allan Camaisa, CEO and Chairman of the Board at Calidi Biotherapeutics. "In our CLD-101 program, NeuroNova’s safety and tolerability observed in the patients dosed thus far, reaffirms our belief in the combination of neural stem cells and antitumor viruses as a potentially transformative therapy for high-grade glioma patients. We are encouraged by the initial safety profile of cohorts 2 and 3, enabling the ongoing recruitment and dosing of the fourth cohort. Along with our clinical progress, we continue to be excited by our novel preclinical programs, RTNova (CLD-400), and look forward to filing our IND application with the FDA on Supernova (CLD-201) for a future phase 1 clinical trial, with their potential ability to treat a diverse set of solid tumors."

Key highlights from the company’s three presentations at ASCO (Free ASCO Whitepaper) are below:

Poster Title: Phase 1 study of multiple intracerebral doses of a neural stem cell-based oncolytic virotherapy for treatment of recurrent high-grade gliomas

Abstract Number: TPS2102

Session Title: Central Nervous System Tumors

CLD-101 is a cutting-edge therapeutic candidate in Calidi’s NeuroNova program, comprising tumor-tropic neural stem cells (NSCs) that deliver an oncolytic adenovirus – CRAd-S-pk7 – selectively to tumor sites.
The study focuses on the safety and feasibility of delivering up to four weekly intracerebral doses of CRAd-S-pk7 to patients with recurrent high-grade gliomas.
All participants receive a uniform dose of 1.50 x 108 NSCs and 1.875 x 1011 viral particles, the maximum feasible dose from the initial human study.
Secondary objectives for the study include assessing the biological activity, biodistribution, immunogenicity, safety, and preliminary clinical efficacy of CRAd-S-pk7.
The initial patient began treatment in May 2023. Currently, three patients in Treatment Schedule 2 and three in Treatment Schedule 3 have been enrolled and treated safely.
Calidi is currently enrolling patients in Treatment Schedule 4.
Poster Title: Transforming tumor immune microenvironments with a novel systemic enveloped oncolytic virotherapy targeting all tumor sites

Abstract Number: 2559

Session Title: Developmental Therapeutics – Immunotherapy

Calidi’s RTNova (CLD-400) systemic antitumor virotherapy platform is a novel tumor-selective vaccinia virus strain, a program designed to target all tumor sites and capable of producing a high amount of enveloped vaccinia viruses (envRTs) resistant to humoral immunity.
The technology allows the therapy to reach every tumor systemically, killing tumor cells, and expressing any desired protein within the tumor, thus modifying the tumor microenvironment.
In preclinical murine models, envRT-01 targeted multiple tumor types and led to tumor growth inhibition with a single systemic injection of 4.5e6 PFU env-RT-01
envRT-01 induced changes in tumor immune microenvironment, targeted lung cancer and metastatic sites, and induced dramatic changes in lung metastasis tumor microenvironments.
Poster Title: Non-clinical evidence supporting the upcoming SuperNova (CLD-201) clinical trial: Cell-based oncolytic virotherapy for multiple solid tumors

Abstract Number: 2553

Session Title: Developmental Therapeutics – Immunotherapy

Animals treated with the maximum tolerated dose of 2e6 PU/animal showed no signs of adverse toxicity and exhibited a reduction in tumor volume compared to the control group.
No toxicity findings were associated with CLD-201 in the disease-free model, and additionally, virus detection in the lungs was cleared within two weeks following the last CLD-201 treatment.
CLD-201 induced potent cytolysis across multiple cancer types in in-vitro models.
Local administration of CLD-201 induced both robust local and systemic immune cell infiltration.
Calidi is expecting to initiate a Phase 1 non-randomized trial to assess the safety and initial anti-tumor effects of CLD-201 administered intratumorally.
Copies of the posters are available on the Publications section of Calidi’s website.

On June 3, 2024 IDRx, Inc., a clinical-stage biopharmaceutical company dedicated to transforming cancer treatment with purpose-built precision therapies, reported updated preliminary clinical data from the Phase 1 portion of the company’s ongoing StrateGIST 1 study of IDRX-42 in patients with advanced gastrointestinal stromal tumors (GIST) (Press release, IDRx, JUN 3, 2024, View Source [SID1234644065]). These data will be highlighted today in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

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IDRX-42 is a novel, KIT mutant-selective, tyrosine kinase inhibitor (TKI) that has potent activity against both the key activating mutations and broad coverage of the clinically relevant resistance mutations in KIT-driven GIST. IDRX-42 was designed to overcome the twin challenges of on-target treatment resistance and off-target driven adverse events, which limit the clinical benefit of currently available TKIs.

"There is a significant unmet medical need for next-generation therapies for GIST patients. Current standards of care either lack the breadth of resistance mutation coverage necessary for patients to realize long durations of response or disease stabilization, or they lack selectivity, resulting in unwanted side effects, or both," said Professor Patrick Schöffski, M.D., M.P.H., Head of the Department of General Medical Oncology at the University Hospitals Leuven. "These promising Phase 1 data support the potential of IDRX-42 to provide meaningful clinical benefit for GIST patients, with encouraging evidence of clinical activity in patients with activating KIT mutations in exons 9 and 11, as well as in patients with clinically relevant resistance mutations in KIT, importantly those in exons 13 and 17."

Updated Preliminary Clinical Data Summary

As of the data cut-off date of April 28, 2024, 73 patients have been treated with IDRX-42 in the Phase 1 portion of the ongoing StrateGIST 1 trial across dose cohorts ranging from 120 mg once daily (QD) to 600 mg twice daily (BID). All 73 patients had KIT-mutant GIST. 66 patients were evaluable for efficacy as of the time of the data cut-off. Patients who were efficacy evaluable must have had at least 1 post-baseline tumor assessment or had clinical progression or death before the first post-baseline tumor assessment.
While a maximum tolerated dose was not reached, dose escalation in the Phase 1 portion of the trial has completed, and the Phase 1b dose confirmation portion of the trial has been initiated utilizing a dose of 300mg tablet formulation, which is equivalent to the 400mg capsule formulation.
Patients were heavily pretreated, with a median of four prior lines of therapy.
19% (14/73) patients had received one prior line of therapy.
11% (8/73) patients had received two prior lines of therapy.
70% (51/73) patients had received three or more prior lines of therapy.
74% of patients remained on study treatment, and the median duration of treatment was 16 weeks as of the data cut-off.
100% of second line patients remained on treatment as of the data cut-off.
The objective response rate (ORR) by modified RECIST v1.1 in the efficacy evaluable population was 23% (15/66) treated across all lines of therapy, of which all were partial responses (12 confirmed PRs, 3 pending confirmation).
The ORR across second line patients was 43% (6/14; 4 confirmed PRs, 2 pending confirmation).
In analyses of circulating tumor DNA (ctDNA), reductions in mutant allele fraction were observed consistently across KIT mutations detected in baseline samples.
Reductions in mutant allele fraction, including to undetectable levels, as best response were observed in exon 9 and 11 activating mutations, and in resistance mutations exon 13, 14, and 17.
IDRX-42 exhibited a favorable safety profile and treatment-related adverse events (TRAEs) were mainly low grade.
The most frequently reported TRAEs (≥20%) were gastrointestinal symptoms (diarrhea, nausea, decreased appetite, vomiting, dysgeusia) and fatigue.
Gastrointestinal adverse events were Grade 1 in most patients, when they occurred.
A low rate of dose modifications due to TRAEs was observed at the 400mg QD dose level, with only 6% dose reductions, 9% dose interruptions, and 0% discontinuations due to TRAEs.
Dose-limiting toxicities (DLTs) were observed in 3/73 patients at doses of 600 mg, 800 mg and 1200 mg, respectively. All 3 patients elected to reduce dose and remained on study as of the data cut-off (range: >3 to >11 months); 2 of these patients have achieved a confirmed PR at a reduced dose of 400 mg QD.
A flat and dose-linear pharmacokinetic profile was observed.
"In this dataset, IDRx has presented preliminary proof-of-concept of IDRX-42 supporting its potentially best-in-class profile in patients with GIST," said Tim Clackson, Ph.D., Chief Executive Officer of IDRx. "Importantly, we believe these efficacy and safety data support our plan to move IDRX-42 rapidly into early lines of therapy, including second-line and front-line, where patients haven’t seen a new treatment option in over 15 years."

"We are excited for these data to be presented today, as they support all aspects of our target product profile, including evidence of potent activity against relevant activating and resistance mutations in KIT, combined with a favorable safety profile," said David Kerstein, M.D., Chief Medical Officer of IDRx. "Across a wide dose range and in this heavily pre-treated patient population, promising signs of clinical activity have been observed, and the initial data compares favorably against approved therapies and those in clinical development. We are encouraged by the emerging safety and tolerability profile, characterized mainly by low grade, manageable gastrointestinal adverse events with a notable lack of adverse events generally associated with off-target activity, such as hand-foot skin reaction and hypertension, supporting the overall selectivity of the molecule. We would like to express our gratitude to the patients and investigators for their participation in the ongoing StrateGIST 1 study."

The Data Will be Highlighted in an Oral Presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting:

Title: StrateGIST 1: A first-in-human (FIH), phase 1 study of IDRX-42 in patients with metastatic gastrointestinal stromal tumors resistant to prior treatment with tyrosine kinase inhibitors (TKIs)
Presenter: Patrick Schöffski, M.D., M.P.H.
Abstract Number: 11501
Presentation Type: Oral Abstract Session
Session Title: Sarcoma (Sub Track Gastrointestinal Stromal Tumors)
Time: 3:12 P.M. CDT

About GIST

Gastrointestinal stromal tumors (GIST) are the most common subtype of soft tissue sarcoma. Approximately 80% of cases arise from gain of function mutations in the KIT receptor tyrosine kinase, driving the malignancy through constitutive activation of aberrant signaling. Resistance mutations in KIT emerge in ~90% of patients treated with imatinib, the current standard of care for GIST. In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type.

About the StrateGIST 1 Study

StrateGIST 1 is an ongoing, open-label, first-in-human Phase 1/1b study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of IDRX-42 in patients with metastatic and/or surgically unresectable GIST after failure of imatinib and other approved drugs. The study is currently enrolling patients with documented pathogenic mutation in KIT or any platelet-derived growth factor receptor alpha (PDGFRA) mutation (other than PDGFRA exon 18) at sites in the U.S., Belgium, Germany and Spain. The Phase 1b portion will include expanded exploratory cohorts based on defined lines of prior TKI therapy.

About IDRX-42

IDRX-42 is a potent, oral, highly selective KIT inhibitor targeting all major categories of activating and resistance mutations in patients with KIT-mutant GIST (including variants in exons 9, 11, 13 and 17). In preclinical studies, IDRX-42 demonstrated superior antitumor activity compared to imatinib, the current first-line of therapy, in GIST human xenograft models expressing mutations in KIT exons 9 and 11. In xenograft models expressing secondary resistance mutations in KIT exon 13 or 17, IDRX-42 treatment resulted in potent and dose-dependent antitumor activity superior to the second-line standard of care agent, sunitinib. IDRX-42 is currently being evaluated in a first-in-human Phase 1/1b study.

On June 3, 2024 Fulgent Pharma, a subsidiary of Fulgent Genetics, Inc. (NASDAQ: FLGT) and a leading nanobiotechnology company specializing in innovative cancer therapeutics, reported that Phase 1 clinical data on its lead therapeutic development candidate, FID-007, to treat Head and Neck cancer, was presented at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on June 2, 2024 in Chicago, Illinois (Press release, Fulgent Pharma, JUN 3, 2024, View Source [SID1234644064]).

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Of eleven head and neck squamous cell carcinoma (HNSCC) evaluable patients with weekly dose levels from 15 mg/m2 to 160 mg/m2, five (45%) had a partial response and three (27%) had stable disease by RECIST. Three out of five HNSCC patients with PR had previously been treated with taxane. The duration of follow-up (months), median (range) is 4.0 (1.0 – 15.0). No high-grade neuropathy has been noted to date. FID-007 demonstrates preliminary evidence of anti-tumor activity in heavily pre-treated HNSCC patients across different primary tumor sites, with an overall response rate of 45%. Phase 2 study of FID-007 combination with cetuximab in patients with HNSCC has begun enrollment.

Commenting on the data, Ming Hsieh, Chairman of the Board and Chief Executive Officer, said, "We are very encouraged by the data from these Head and Neck cancer patients, in particular the preliminary evidence of relatively lower toxicity and improved treatment tolerance with FID-007 compared to prior therapies. These data support the Phase 2 clinical study we recently began in head and neck squamous cell carcinoma, and we look forward to bringing FID-007 to more patients as we continue enrollment."

The poster is available on the News & Events section of the company’s Investor Relations website at View Source

About FID-007

FID-007 consists of paclitaxel encapsulated in a polyethyloxazoline (PEOX) polymer excipient designed to enhance PK, biodistribution, and tolerability. In addition to allowing the drug to remain in solution until it can enter a cancer cell, the PEOX nanoparticle is designed to preferentially deliver paclitaxel to the tumor through the leaky hyperpermeable vasculature.

On June 3, 2024 Novocure (NASDAQ: NVCR) reported the presentation of clinical data from the phase 3 METIS trial, which investigated the use of Tumor Treating Fields (TTFields) therapy in the treatment of brain metastases from non-small cell lung cancer (NSCLC) (Press release, NovoCure, JUN 3, 2024, View Source [SID1234644063]). These data will be presented at the ongoing 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago.

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The METIS trial enrolled 298 adult patients with 1-10 brain metastases from NSCLC, who were randomized following stereotactic radiosurgery (SRS) to receive either TTFields therapy and best supportive care (BSC) (n=149) or BSC alone (n=149). METIS met its primary endpoint, demonstrating a statistically significant improvement in time to intracranial progression. Patients treated with TTFields therapy and BSC exhibited a median time to intracranial progression of 21.9 months compared to 11.3 months in patients treated with BSC alone (hazard ratio=0.67; P=0.016). Median TTFields therapy duration was 16 weeks and median usage was 67%. Baseline patient demographics and characteristics were well balanced between arms.

Patients treated with TTFields therapy demonstrated improved quality of life deterioration-free survival, with median time to quality of life deterioration-free survival not reached in the TTFields therapy cohort compared to 7.7 months in control arm (P=0.038). A positive trend was observed in patients treated with TTFields therapy in the majority of scales and items assessed by the EORTC QLQ C30 and BN20 patient questionnaire. There was no evidence of worsening cognitive functioning in the TTFields therapy arm compared to the control arm. Consistent with prior clinical trials, TTFields therapy was well-tolerated with no additive systemic toxicity.

Preliminary analyses of key secondary endpoints did not demonstrate statistical significance. Median overall survival for patients randomized to receive TTFields therapy and BSC was 11.3 months compared to 10.6 months in patients treated with BSC alone. Full analysis of secondary endpoints is ongoing.

"One of the key challenges in combatting the spread of brain metastases is maintaining patients’ quality of life and cognitive function," said lead investigator Minesh Mehta, MD, Chief of Radiation Oncology and Deputy Director at Miami Cancer Institute, part of Baptist Health South Florida. "The ability of TTFields therapy to prolong the time to intracranial progression without negatively impacting either quality of life or cognitive function has the potential to change the way brain metastases from non-small cell lung cancer are treated."

"Despite the high incidence level of brain metastases from NSCLC, the treatment options available for patients are very limited," said Nicolas Leupin, MD, Novocure’s Chief Medical Officer. "The observations from the METIS trial are an important first step in potentially adding a new treatment option for these patients and we are eager to pursue the necessary steps to ensure TTFields therapy is available to those in need."

These data will be featured by Dr. Mehta in an oral presentation (abstract #2008) at 10:24 a.m. CDT on Monday, June 3, 2024 during ASCO (Free ASCO Whitepaper)’s Central Nervous System Tumors session. Novocure intends to publish these findings in a peer-reviewed scientific journal and submit these data to regulatory authorities.

About METIS

METIS [NCT02831959] is a phase 3 trial of stereotactic radiosurgery with or without TTFields therapy for patients with 1-10 brain metastases from NSCLC. 298 adult patients were enrolled in the trial and randomized to receive either TTFields therapy with supportive care or supportive care alone following SRS. Supportive care consisted of, but was not limited to, treatment with steroids, anti-epileptic drugs, anticoagulants, pain control or nausea control medications. Patients in both arms of the study were eligible to receive systemic therapy for their NSCLC at the discretion of their treating physician. Patients with known tumor mutations for which targeted agents are available were excluded from the trial.

The primary endpoint of the METIS trial is time to first intracranial progression, as measured from the date of first SRS treatment to intracranial progression or neurological death (per RANO-BM criteria), whichever occurs first. Time to intracranial progression was calculated according to the cumulative incident function. Patient scans were evaluated by a blinded, independent radiologic review committee. Secondary endpoints include, but are not limited to, time to distant progression, time to neurocognitive failure, overall survival, time to second intracranial progression, quality of life and adverse events. Key secondary endpoints (time to neurocognitive failure, overall survival, and radiological response rate) were planned to be used in labeling claims, if successful. Full analysis of secondary endpoints is ongoing. Patients were stratified by the number of brain metastases (1-4 or 5-10 metastases), prior systemic therapy, and tumor histology. Patients were allowed to crossover to the experimental TTFields therapy arm following confirmation of second intracranial progression.

About Tumor Treating Fields Therapy

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. The multiple, distinct mechanisms of TTFields therapy work together to selectively target and kill cancer cells. Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or targeted therapies in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors. To learn more about Tumor Treating Fields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.