On June 4, 2024 National Cancer Center (President: Hitoshi Nakagama) Hospital East (Director: Toshihiko Doi) and PeptiDream Inc., a public Kanagawa, Japan-based biopharmaceutical company (President: Patrick C. Reid, hereinafter "PeptiDream")(Tokyo: 4587) reported the dosing of the first patient in the human imaging study of PeptiDream’s 64Cu-PD-32766, a 64Cu-labelled radiopharmaceutical targeting Carbonic Anhydrase IX (CAIX), for patients with clear cell renal cell carcinoma (ccRCC) conducted at the National Cancer Center Hospital East ("the clinical research") (Press release, National Cancer Center of Japan, JUN 4, 2024, View Source [SID1234644110]).

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!

Details

The clinical research, which was approved by the National Cancer Center Japan’s clinical review board in April 2024, is a first-in-human imaging study of 64Cu-PD-32766 conducted in collaboration with the National Cancer Center Japan and PeptiDream. This study is intended to evaluate the safety, pharmacokinetics, and accumulation of 64Cu-PD-32766 in tumors using PET in patients with newly diagnosed, relapsed or suspected relapsed ccRCC.

Overview of Clinical Research

Title

Early-phase clinical trial of 64Cu-PD-32766 for the patients with clear cell renal cell carcinoma

Principal Investigator

Anri Inaki (National Cancer Center Hospital East)

Objectives

To evaluate the safety, pharmacokinetics, and exposure dose of PET/CT test with 64Cu-PD-32766 in patients with newly diagnosed, relapsed or suspected to have relapsed ccRCC.

Inclusion Criteria

Proven ccRCC patients with the presence of distant metastatic lesions (including distant metastatic recurrence) or local recurrence lesions from the site of removal after total nephrectomy of the diseased kidney

Number of Subjects

6

Primary outcome

Per-patient PET sensitivity

Secondary outcomes

Per-lesion PET sensitivity, safety, pharmacokinetics and estimated irradiation dose

JRCT trial identifier: jRCTs031240046

CAIX is a cell surface antigen highly expressed in ~95% of ccRCC with minimal expression in normal tissues, making it a potentially ideal target for the diagnosis and treatment of ccRCC. PeptiDream discovered and developed PD-32766 using its proprietary Peptide Discovery Platform System (PDPS) technology, with in vivo imaging and efficacy studies conducted by PDRadiopharma Inc. (PeptiDream’s wholly owned subsidiary). Key advantages of this clinical research are the ability to generate early human imaging data (often referred to as a Phase 0 study) using diagnostic 64Cu agent directly in the target patient population which provides an early look at the diagnostic usefulness of the agent, the likelihood of therapeutic benefit when labeled with a therapeutic radioisotope, and additional critical information that can be used in designing subsequent clinical studies, thereby significantly accelerating clinical development.

Comments of Dr. Toshihiko Doi, Director, National Cancer Center Hospital East

We are delighted to report the initiation of this human imaging study, with the first administration of 64Cu-PD-32766 in patients diagnosed with ccRCC. As one of the leading cancer centers in Japan, our mission is to continuously improve healthcare in Japan, by bringing innovative life changing therapeutics to our patients in need, and we believe that combining PeptiDream’s cancer targeting peptides with the imaging and cancer killing power of radionuclides, represents a highly promising new therapeutic approach toward the diagnosis and treatment of patients with ccRCC.

Comments of Dr. Patrick C. Reid, President & CEO of PeptiDream

We are excited to announce that our collaborators at the National Cancer Center Japan have dosed the first patient in the human imaging study of PD-32766, our CAIX targeting macrocyclic peptide radiolabeled with 64Cu, for the potential diagnosis and treatment of patients with ccRCC. I am extremely proud of the entire PeptiDream team, and grateful to our National Cancer Center Japan collaborators, for this wonderful achievement, and we look forward to sharing the results as they become available. We are deeply committed to utilizing our peptide expertise to develop the next generation of targeted radiopharmaceuticals, which we believe will have a tremendous impact on cancer patient care.

About Renal Cell Carcinoma (RCC)

RCC is the 9th most common cancer in the United States, representing 2% of all global cancer diagnoses and death, with 5-year survival rates at 12% (worldwide an estimated 400,000 people were diagnosed with kidney cancer in 2020, with roughly 9 out of 10 kidney cancers being RCCs). There are largely three main types of RCC, clear cell ("ccRCC"), papillary ("pRCC-type 1 and type 2"), and chromophobe ("chRCC"), with ccRCC representing roughly 70% of RCC cases.

Reference

A novel Carbonic Anhydrase IX targeting radiopeptide, 64Cu-PD-32766 and 177Lu-PD32766, exhibit promising theranostic potential in ccRCC tumors. (American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024)

Glossary

(Note) Radiotheranostics
Radiotheranostics refers to the use of radioisotope-labelled agents to diagnose and treat patients by using different nuclides. Theranostics integrate the diagnosis and treatment of cancer, narrow down patients who is likely to be effective in treatment and monitor the effectiveness of treatment.

On June 4, 2024 Guardant Health, Inc. (NASDAQ:GH), a leading precision oncology company, reported the launch of a new version of its Guardant360 TissueNext test that expands the number of genes it identifies in a tumor tissue sample to 498 (Press release, Guardant Health, JUN 4, 2024, View Source [SID1234644109])c. These genes, or cancer biomarkers, enable oncologists to identify the targeted therapies or treatment strategies that are most effective for patients with advanced cancer. In addition to the panel expansion, Guardant has improved the test’s operational workflow for a faster turnaround time.

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 new Guardant360 TissueNext test will be covered for Medicare fee-for-service patients with advanced solid tumor cancers as a standalone service, based on coverage conveyed by Palmetto GBA, a Medicare administrative contractor for the Molecular Diagnostics Services program (MolDX), under the existing local coverage determination.

"The launch of the new Guardant360 TissueNext test is another step forward in our mission to conquer cancer with data," said Helmy Eltouky, Guardant Health chairman and co-CEO. "In addition to identifying guideline-recommended biomarkers, the upgraded test now provides more comprehensive gene coverage, so oncologists can make better informed decisions about the optimal treatment strategy for their patients with advanced cancer and help improve their outcomes."

Guardant360 TissueNext identifies clinically relevant actionable biomarkers in tumor tissue to help oncologists select patients with advanced cancer who may benefit from biomarker-informed treatment. Results are provided in less than two weeks.

The test, which first received Medicare coverage in March 2022, is part of Guardant’s comprehensive portfolio of blood- and tissue-based genomic profiling tests, including Guardant360 CDx, the first liquid biopsy test approved by the FDA for comprehensive genomic profiling of all solid tumors. The Guardant360 TissueNext test can be ordered alone or in combination with Guardant360 CDx to support guideline-recommended complementary liquid and tissue genomic profiling testing for advanced breast and lung cancer.

On June 4, 2024 MAIA Biotechnology, Inc., (NYSE American: MAIA) ("MAIA", the "Company"), a clinical-stage biopharmaceutical company developing targeted immunotherapies for cancer, reported new efficacy data from its Phase 2 THIO-101 clinical trial evaluating THIO sequenced with the immune checkpoint inhibitor (CPI) cemiplimab (Libtayo) in patients with advanced non-small cell lung cancer (NSCLC) who failed 2 or more standard-of-care therapy regimens (Press release, MAIA Biotechnology, JUN 4, 2024, View Source [SID1234644108]). Updated results show a favorable overall response rate (ORR) of 38% and a disease control rate (DCR) of 85% from THIO + CPI in third-line treatment. The new data was presented in a poster session at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2024 Annual Meeting on June 3, 2024.

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 primary objectives of THIO-101 Phase 2 trial are to examine the safety and tolerability of THIO as an anticancer drug and as an immune system primer, and to examine the clinical efficacy of THIO in the form of ORR. At the time of the most recent data cut-off (April 30, 2024), all evaluable patients had completed ≥1 post-baseline assessment.

Results from third-line treatment:

Disease control rate (DCR) was 85% for THIO vs. standard of care DCR of 25–35% for chemotherapy1
65% of patients crossed the 5.8-month overall survival (OS) threshold2
85% of patients crossed the 2.5-month progression-free survival (PFS) threshold3-4
Median survival follow-up time is currently 9.1 months (n=20)
Results from third-line treatment with THIO 180mg (optimal dose selection)

Median PFS of 5.5 months (24.1 weeks)
78% OS rate at 6 months
38% ORR vs. standard of care 6–10% for chemotherapy2
75% of patients crossed the 5.8-month OS threshold2
88% of patients crossed the 2.5-month PFS threshold3-4
Median survival follow-up time is currently 9.1 months (n=8)
1 Matsumoto H, et al. Transl Lung Cancer Res 2021;10:2278–89.
2 Girard N, et al. J Thorac Onc 2009;12:1544-1549.
3 Shepherd F, et al. N Engl J Med 2005;353:123-132.
4 Fossella F, et al. J Clin Oncol 2000;18(12):2354-62.

"All exceptional measures of efficacy in our trial to date have exceeded our own expectations and outperformed standard of care treatments," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "The data presented at ASCO (Free ASCO Whitepaper) advances THIO’s excellent clinical profile as a strong, safe, and highly effective alternative for patients who progressed following chemotherapy and other available treatments. We eagerly anticipate full efficacy data from THIO-101 in the second half of this year."

To date, treatment with THIO + cemiplimab has been generally well tolerated in a heavily pre-treated patient population. Full enrollment in THIO-101 was completed on February 19, 2024, earlier than expected as per trial design. The Company expects that THIO-101 will be the first completed clinical study of a telomere targeting agent in the field of cancer drug discovery and treatment.

The poster and updated Company presentations can be accessed on the company’s website.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is a first-in-class investigational telomere-targeting agent currently in clinical development to evaluate its activity in Non-Small Cell Lung Cancer (NSCLC). Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. The modified nucleotide 6-thio-2’-deoxyguanosine (THIO) induces telomerase-dependent telomeric DNA modification, DNA damage responses, and selective cancer cell death. THIO-damaged telomeric fragments accumulate in cytosolic micronuclei and activates both innate (cGAS/STING) and adaptive (T-cell) immune responses. The sequential treatment with THIO followed by PD-(L)1 inhibitors resulted in profound and persistent tumor regression in advanced, in vivo cancer models by induction of cancer type–specific immune memory. THIO is presently developed as a second or later line of treatment for NSCLC for patients that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

About THIO-101, a Phase 2 Clinical Trial

THIO-101 is a multicenter, open-label, dose finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s anti-tumor activity when followed by PD-(L)1 inhibition. The trial is testing the hypothesis that low doses of THIO administered prior to cemiplimab (Libtayo) will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or developed resistance and progressed after first-line treatment regimen containing another checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety and tolerability of THIO administered as an anticancer compound and a priming immune activator (2) to assess the clinical efficacy of THIO using Overall Response Rate (ORR) as the primary clinical endpoint. Treatment with cemiplimab (Libtayo) followed by THIO has been generally well-tolerated to date in a heavily pre-treated population. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.

On June 4, 2024 Beijing Avistone Biotechnology Co., Ltd. (also referred to as Avistone Biotechnology or Avistone), an innovative biotechnology company focused on precision oncology therapeutics, reported results from the two presentations at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL (Press release, Avistone Pharmaceuticals, JUN 4, 2024, View Source [SID1234644107]).

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!

Details and highlights from the presentations are as follows:

Oral Presentation:
Title: Efficacy and safety of the Vebreltinib in previously treated, secondary glioblastoma / IDH mutant glioblastoma patients with PTPRZ1-METFUsion GENe (FUGEN): a randomised, multicentre, open-label, phase II/III trial
Presenter: Zhaoshi Bao, MD, PhD Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China
Session Title: Central Nervous System Tumors
Published Abstract Number: 2003

Isocitrate dehydrogenase (IDH)-mutant gliomas carry a high risk of malignant transformation from low-grade gliomas into high-grade gliomas within 10 years, resulting in poor prognosis. Effective targeted drugs for high-grade gliomas are still lacking.

In this open-label, phase II/III trial, 84 patients with histologically confirmed secondary GBM or IDH-mutant GBM were assigned in a 1:1 ratio to receive twice-daily oral vebreltinib at a 300 mg dose or the investigator’s choice of chemotherapy (temozolomide [100-150 mg/m2/day, 7 days on followed by 7 days off ]) or cis-platinum [80-100 mg/m2 for 3 days] combined with etoposide [100mg/m2/day for 3 days]) every 28 days. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and objective response rate (ORR).

42 patients of the vebreltinib group and 39 patients of the chemotherapy group were included in the full analysis set. After a median follow-up of 4.44 months, the median OS in the vebreltinib group and chemotherapy group was 6.31 months (95% CI, 4.44-8.77) and 3.38 months (95% CI, 2.37-4.27), respectively. The HR for OS was 0.52 (90% CI, 0.32-0.85; P = 0.009). The median PFS in the vebreltinib group and chemotherapy group was 1.87 months (95% CI, 1.41-2.76) and 1.05 months (95% CI, 0.95-1.77), respectively. The HR for PFS was 0.54 (95% CI, 0.33-0.88; P = 0.014). No significant differences were observed in ORR (9.5% vs. 2.6%) for the vebreltinib group and chemotherapy group.

Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the vebreltinib group, as compared with 12.2% of those in the chemotherapy group. No treatment-related deaths were observed.

These results of the FUGEN trial support the use of vebreltinib as the first target therapy in patients with previously treated, PTPRZ1-MET fusion gene positive, secondary glioblastoma / IDH-mutant glioblastoma, and shed light on a novel therapeutic pathway in the landscape of IDH-mutant high-grade gliomas.

"The development of drugs for indications related to MET targets has always been a difficult one. This is not only a victory for translational medicine, but also marks the advent of the era of targeted therapy in the field of brain glioma," said Dr. Hepeng Shi, Chairman, CEO, and Founder of Avistone.

Clinical Trials Information: NCT06105619 and ChiCTR2300077783

Poster Presentation:
Title: Efficacy and Safety of Vebreltinib in Patients with Advanced NSCLC Harboring MET Exon 14-Skipping: Results of 2.5-year follow-up in KUNPENG
Presenter: Jin-Ji Yang, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
Session Title: Lung Cancer – Non-Small Cell Metastatic
Abstract Number: 8557

MET exon 14 skipping mutation is present approximately 3% to 4% of non-small cell lung cancers (NSCLCs) and is associated with poorer survival rates. Vebreltinib (PLB1001), a potent and highly selective c-MET inhibitor, demonstrated superior objective response rate (ORR) benefits in locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients (pts) with MET exon 14 (METex14) skipping mutations in the previous analysis of the phase II KUNPENG study.

In this Phase II, open-label, multicenter, and multi-cohort study, tumor tissue was assessed for METex14 skipping mutation using next-generation sequencing (NGS) from CAP or CLIA certificated local or central laboratories. Patients in Cohort 1 received 200 mg of vebreltinib twice daily (28 days per cycle) until discontinuation criteria were met. The primary endpoint was ORR assessed by blinded independent review committee (BIRC).

Between Jan 17, 2020 and Feb 09, 2021, 52 patients were enrolled in Cohort 1. As of the data cutoff date (Aug 09, 2023), the median duration of follow-up was 19.1 months (range, 1.0-42.7) and the median duration of treatment was 9.9 months (range, 0.6-42.7). Per BIRC assessment, the ORR was 75% (95% CI: 61.1-86.0), the disease control rate (DCR) was 96.2% (95% CI 86.8-99.5), the median duration of response (DoR) was 16.5 months (95% CI 9.2-19.4), the median time to response (TTR) was 1.0 month (95% CI 1.0-2.8), the median progression-free survival (PFS) was 14.3 months (95% CI 6.4-18.2), and the median overall survival (OS) was 20.3 months (95% CI 16.2-29.7). The 3-year OS rate was 35.1%. Subgroup analyses showed the ORR was 100.0%, 66.7%, 85.7% and 100.0% among pts with any baseline brain metastases (N=5), pts with any baseline liver metastases (N=6), pts aged 75 years and older (N=21) and pts with co-occurring of MET amplification (N=12), respectively.

The most common (≥20%) treatment-related adverse events (TRAEs) in all of the 135 patients enrolled in this study were peripheral edema (56.3%), hypoalbuminemia (27.4%), hypoproteinemia (25.9%) and anemia (20.7%).

"With this study, we continue to see best-in-class potential of Vebreltinib in patients with MET exon 14 skipping mutation NSCLC," said Dr. Hepeng Shi, Chairman, CEO, and Founder of Avistone.

Clinical trial information: NCT04258033

On June 4, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to lunresertib in combination with camonsertib for the treatment of adult patients with CCNE1 amplified, or FBXW7 or PPP2R1A-mutated platinum-resistant ovarian cancer (Press release, Repare Therapeutics, JUN 4, 2024, View Source [SID1234644106]).

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!

Lunresertib in combination with camonsertib is currently being evaluated in Repare’s MYTHIC Module 2 Phase 1 dose expansion clinical trial at the recommended Phase 2 dose in patients with ovarian and endometrial cancers harboring CCNE1 amplification or FBXW7 or PPP2R1A mutations. In addition to the Fast Track designation announced today, the FDA previously granted Fast Track designation to lunresertib in combination with camonsertib for the treatment of adult patients with CCNE1 amplified, or FBXW7 or PPP2R1A mutated endometrial cancer in the third quarter of 2023. Repare expects to present data from the MYTHIC Module 2 dose expansion cohorts in approximately 20-30 patients each with ovarian and endometrial cancer in the fourth quarter of 2024.

"The FDA’s decision to grant Fast Track designation supports our goal of quickly and efficiently developing the lunresertib-camonsertib combination for patients with genomically-defined platinum-resistant ovarian cancer," said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. "Ovarian cancer patients need therapies that provide long-term benefit beyond that observed with standard of care. Our precision medicine approach targets treatment to patients who could most benefit from a well-tolerated alternative to chemotherapy."

The FDA’s Fast Track process is designed to facilitate the development and expedite the review of therapies intended to treat serious conditions and address unmet medical needs to potentially bring important new medicines to patients earlier. Companies whose programs are granted FTD are eligible for more frequent interactions with the FDA during clinical development and potentially accelerated approval and/or priority review, if relevant criteria are met. For more information on Fast Track Designation, please visit the FDA’s website at View Source

About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.