On October 23, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported the presentation of early clinical data from the ongoing Phase 1/2 CARE study in pediatric and young adult patients with advanced solid tumors harboring ALK, ROS1 or NTRK alterations (Press release, Turning Point Therapeutics, OCT 23, 2021, View Source [SID1234591834]). These data are being presented today at the virtual 53rd Congress of the International Society of Paediatric Oncology (SIOP) being held October 21-24.

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"These early data for repotrectinib demonstrate encouraging clinical activity in this pediatric patient population," said Mohammad Hirmand, M.D., chief medical officer. "Patient enrollment is continuing in the Phase 1/2 CARE study, and we look forward to further advancing the development of repotrectinib in this patient population."

Early Data from Phase 1/2 CARE Study
The primary objective of the Phase 1 dose escalation portion of the study is to evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) of repotrectinib in pediatric patients less than 12 years old. The primary objective of the Phase 2 portion of the study is to determine the anti-tumor activity of repotrectinib in pediatric and young adult patients less than 25 years old. Repotrectinib is administrated in capsule or suspension formulation using weight-based dosing for patients less than 12 years old. Patients 12 to 25 years old can enroll directly into the Phase 2 portion of the study with a repotrectinib dose of 160 mg QD for the first 14 days and may increase to 160 mg BID thereafter.

The early Phase 1/2 CARE dataset utilizes an August 2, 2021 data cutoff date. Ten patients were treated across two dose levels. The safety analysis includes the ten treated patients, and the preliminary efficacy analysis includes eight evaluable patients. Patients included in the efficacy analysis had baseline measurable disease and at least one post-baseline evaluable scan. Response evaluation was by physician assessment and per RECIST v1.1 or RANO for CNS tumors. Responses were confirmed with a subsequent scan at least 28 days later.

The findings were reported in a pre-recorded presentation by Steven G. Dubois, M.D., associate professor of Pediatrics, Harvard Medical School available on October 23 at 9:12 a.m. ET on the meeting website.

Preliminary Safety Analysis (n=10) and Pharmacokinetic Analysis

Repotrectinib was generally well tolerated.

The most frequently reported treatment-emergent adverse events (TEAEs) were anemia (n=5) and fatigue (n=5). Among patients with anemia, three had baseline history of anemia.

Dizziness events (n=4) were grade 1 or 2 and none led to treatment discontinuation.

No patients discontinued treatment due to reasons other than disease progression and no patients had TEAEs that led to dose reduction.

No dose-limiting toxicities were reported.

Preliminary pharmacokinetics data indicated that the exposure of repotrectinib in different age groups was comparable to the adult exposure at steady-state.
Preliminary Efficacy Analysis (n=8)

Eight patients were evaluable for efficacy, including four TKI-naïve and four TKI-pretreated patients. TKI-naive patients included those with NTRK amplified anaplastic ependymoma (n=1), NTRK fusion glioblastoma multiforme (GBM)/high grade glioma (n=1), NTRK fusion sarcoma (n=1), and ROS1 fusion inflammatory myofibroblastic tumor (IMT) (n=1). TKI-pretreated patients included those with NTRK fusion GBM/high grade glioma (n=2), NTRK fusion mesoblastic nephroma (n=1), and NTRK fusion sarcoma (n=1).

Three TKI-naïve patients (2 NTRK fusion solid tumors; 1 ROS1 fusion IMT) achieved confirmed responses. One of the three responding patients had a NTRK fusion GBM/high grade glioma, was previously treated with tumor resection, whole brain radiotherapy, and multi-agent chemotherapy, and achieved a complete response (CR) and remained in a response for 3.8+ months as of the data cutoff date. The other two confirmed responders remained in response with duration of response of 7.3+ and 12.1+ months, respectively.

Of the four TKI-pretreated patients, one patient with NTRK fusion sarcoma had a best response of stable disease.
The Phase 1 dose finding portion of the study is ongoing in pediatric patients less than 12 years old to confirm the pediatric RP2D. The Phase 2 portion of the study is ongoing for patients 12 to 25 years old.

Turning Point also announced the publication of preclinical data of repotrectinib in neuroblastoma, the most common pediatric extracranial solid tumor, in the American Association of Cancer Research’s peer reviewed journal, Molecular Cancer Therapeutics. Preclinical studies described in the publication titled "Translational Strategies for Repotrectinib in Neuroblastoma" show that repotrectinib inhibits tumor growth and prolongs survival in patient-derived neuroblastoma xenograft models. In addition, the studies indicated that combining repotrectinib with chemotherapy may be a promising treatment paradigm for neuroblastoma patients.

On October 23, 2021 OncXerna Therapeutics, Inc. ("OncXerna"), a precision medicine company using an innovative RNA-expression based biomarker platform to predict patient responses to its targeted oncology therapeutic candidates, reported new biomarker data from a retrospective analysis of results from its Phase 1b clinical trial of navicixizumab in an electronic poster at the European Society of Gynaecological Oncology (ESGO) Congress 2021 (Press release, OncXerna Therapeutics, OCT 23, 2021, View Source [SID1234591826]).

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Data presented in the poster are from a retrospective analysis of results from an open-label Phase 1b trial evaluating navicixizumab, a potentially first-in-class anti-DLL4/VEGF bispecific antibody targeting tumor vasculature, in combination with paclitaxel in patients with platinum-resistant ovarian cancer (PROC). Pre-treatment biopsies were analyzed using the investigational Xerna TME Panel to retrospectively compare the biomarker classification of patients against clinical outcomes.

"There is a pressing unmet need for new treatments for patients with platinum-resistant ovarian cancer who have progressed on Avastin or failed more than two lines of prior therapy," said Dr. Kathleen Moore, Stephenson Cancer Center, Oklahoma. "I believe the data presented at ESGO demonstrated the potential of navicixizumab together with the Xerna TME Panel to help address this need. The response rate and treatment durability of navicixizumab in this heavily pretreated patient population are very exciting and results showed improved outcomes in patients classified as having a high angiogenesis score by the Xerna TME Panel’s novel, RNA-expression based algorithm. We have been searching for a predictive biomarker for anti-angiogenic therapies and the Xerna TME panel results presented at ESGO are very promising."

Key data and conclusions from the ESGO poster include:

Clinical outcomes were greater in biomarker positive (B+) vs. biomarker negative (B-) patients
Overall response rate (ORR) in B+ patients: 62% (8/13)
ORR in B- patients: 25% (5/20)
ORR across all patients: 43% (19/44)
Disease control rate (DCR) in B+ patients: 100% (13/13)
DCR in B- patients: 65% (13/20)
DCR across all patients: 77% (34/44)

A consistent correlation was seen between B+ subtype and improved progression-free survival (PFS)
Median PFS in B+ patients: 2 months (95% confidence interval: 5.5 – not estimable)
Median PFS in B- patients: 9 months (95% confidence interval: 1.8 – 8.9)

Laura Benjamin, Ph.D., President and Chief Executive Officer of OncXerna, commented, "The retrospective biomarker analyses presented at ESGO provide an important point of validation for the development of the Xerna TME Panel. Our next step is to further explore these findings through a prospective Phase 3 trial of navicixizumab plus paclitaxel that is also designed to quantify the Xerna TME Panel’s predictive value. We look forward to the initiation of this trial and the evaluation of our Xerna TME Panel as a potential companion diagnostic for immuno-oncology and anti-angiogenic agents."

A copy of the ESGO poster (Abstract 918), entitled: "Correlative analyses of a Phase 1b study of navicixizumab plus paclitaxel in patients with platinum-resistant ovarian cancer using the Xerna TME Panel," can be found here.

About the Phase 1b Trial

The Phase 1b trial was an open-label, non-randomized, dose-escalation and expansion study of the safety, tolerability, and efficacy of navicixizumab plus paclitaxel in patients with platinum-resistant ovarian cancer. The trial enrolled patients who previously received Avastin (bevacizumab) and/or more than 2 prior lines of therapy. Patients were treated with navicixizumab once every two weeks together with weekly paclitaxel. The primary endpoint of the trial was incidence of dose limiting toxicities. Secondary endpoints included response rate assessed by RECIST criteria 1.1 and progression-free survival. For more information, see ClinicalTrials.gov Identifier: NCT03030287.

About Navicixizumab

Navicixizumab is an anti-DLL4/VEGF bispecific antibody product candidate that demonstrated antitumor activity in patients who were previously treated with Avastin (bevacizumab) in a Phase 1b clinical trial. The U.S. Food and Drug Administration granted Fast Track designation to navicixizumab for the treatment of high-grade ovarian, primary peritoneal, or fallopian tube cancer in patients who have previously received Avastin and/or more than 2 prior lines of therapy. Navicixizumab is an investigational agent that has not been approved, and it has not been demonstrated to be safe or effective for any use, including for the treatment of advanced ovarian cancer.

About the Xerna TME Panel

The Xerna TME Panel uses proprietary RNA-based gene expression data and a machine learning-based algorithm to classify patients based on the interplay between angiogenic and immunogenic dominant biologies of the tumor microenvironment (TME). The Xerna TME Panel is an investigational assay that has not been approved and has not been demonstrated to be safe or effective for any use.

On October 22, 2021 Theratechnologies Inc. (Theratechnologies, or Company) (TSX: TH) (NASDAQ: THTX), a biopharmaceutical company focused on the development and commercialization of innovative therapies, reported the publication of a peer-reviewed article demonstrating that the Company’s novel investigational peptide-drug conjugates (PDCs) TH1902 and TH1904, derived from its SORT1+ Technology, are effective in inhibiting vasculogenic mimicry (VM) in in vitro ovarian and triple negative breast cancer (TNBC) models (Press release, Theratechnologies, OCT 22, 2021, View Source [SID1234596236]).

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The article was published in the science journal Frontiers in Oncology and is titled "New Peptide-Drug Conjugates for Precise Targeting of SORT1-Mediated Vasculogenic Mimicry in the Tumor Microenvironment of TNBC-Derived MDA-MB-231 Breast and Ovarian ES-2 Clear Cell Carcinoma Cells."

"The results published in Frontiers in Oncology showcase for the first time that the sortilin receptor plays a role in the formation of VM, which is associated with cancer progression and resistance. By targeting SORT1, TH1902 and TH1904 have the potential to inhibit VM and cancer cell growth," said Dr. Christian Marsolais, Senior Vice President and Chief Medical Officer at Theratechnologies. "This recognition by our scientific peers highlights the great potential of our PDCs as a unique and effective vehicle for the potential treatment of many types of cancers in which SORT1 receptors are overexpressed and provides additional evidence that SORT1 plays a major role in the generation of VM, particularly in TNBC and ovarian cancer."

The article is the first to report that SORT1 plays a key role in VM formation and highlights the novel results from preclinical models evaluating the efficient inhibitory properties of TH1902 and TH1904 against VM in in vitro ovarian and TNBC cell models. These results further support the expectation that TH1902 and TH1904 may alter the VM process by bringing anticancer drugs, like docetaxel and doxorubicin, into SORT1-positive cancer cells.

The article can be accessed online here.

About Vasculogenic Mimicry
The formation of microvascular channels by deregulated cancer cells leads to aggressive, metastatic and resistant cancer cells and is known as vasculogenic mimicry. VM is believed to be associated with tumor growth, resistance and poor prognosis in many types of aggressive cancers including ovarian and TNBC.

About SORT1+ Technology
Theratechnologies is currently developing a platform of new proprietary peptides for cancer drug development targeting SORT1 receptors called SORT1+ TechnologyTM. SORT1 is a receptor that plays a significant role in protein internalization, sorting and trafficking. It is highly expressed in cancer cells compared to healthy tissue making it an attractive target for cancer drug development. Expression has been demonstrated in, but not limited to, ovarian, triple-negative breast, endometrial, skin, lung, colorectal and pancreatic cancers. Expression of SORT1 is associated with aggressive disease, poor prognosis and decreased survival. It is estimated that the SORT1 receptor is expressed in 40% to 90% of cases of endometrial, ovarian, colorectal, triple-negative breast and pancreatic cancers.

The Company’s innovative peptide-drug conjugates (PDCs) generated through its SORT1+ TechnologyTM demonstrate distinct pharmacodynamic and pharmacokinetic properties that differentiate them from traditional chemotherapy. In contrast to traditional chemotherapy, Theratechnologies’ proprietary PDCs are designed to enable selective delivery of certain anticancer drugs within the tumor microenvironment, and more importantly, directly inside SORT1 cancer cells. Commercially available anticancer drugs, like docetaxel, doxorubicin or tyrosine kinase inhibitors are conjugated to Theratechnologies’ PDC to specifically target SORT1 receptors. This could potentially improve the efficacy and safety of those agents.

In preclinical data, the Company’s SORT1+ TechnologyTM has shown to improve anti-tumor activity and reduce neutropenia and systemic toxicity compared to traditional chemotherapy. Additionally, in preclinical models, SORT1+ TechnologyTM has shown to bypass the multidrug resistance protein 1 (MDR1; also known as P-glycoprotein) and inhibit the formation of vasculogenic mimicry – two key resistance mechanisms of chemotherapy treatment.

About TH1902
TH1902 combines Theratechnologies’ proprietary peptide to the cytotoxic drug docetaxel. TH1902 is currently Theratechnologies’ lead investigational PDC candidate for the treatment of cancer derived from its SORT1+ Technology. The FDA granted fast track designation to TH1902 as a single agent for the treatment of all sortilin-positive recurrent advanced solid tumors that are refractory to standard therapy. TH1902 is currently being evaluated in a Phase 1 clinical trial for the treatment of cancers where the sortilin receptor is expressed.

The Company is also evaluating TH1904 in preclinical research, a second PDC derived from its SORT1+ TechnologyTM TH1904 is conjugated to the cytotoxic drug doxorubicin.

The Canadian Cancer Society and the Government of Quebec, through the Consortium Québécois sur la découverte du médicament (CQDM), contributes a total of 1.4 million

On October 22, 2021 Aadi Bioscience, Inc. ("Aadi") (Nasdaq: AADI), a clinical-stage biopharmaceutical company focusing on precision therapies for genetically-defined cancers with alterations in mTOR pathway genes, reported the publication of "nab-Sirolimus for Patients with Malignant Perivascular Epithelioid Cell Tumors", detailing its AMPECT study of investigational ABI-009 in the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s Journal of Clinical Oncology (Press release, Aadi Bioscience, OCT 22, 2021, View Source [SID1234592017]). The authors concluded that investigational nab-sirolimus (ABI-009, formerly known as nab-rapamycin), if approved, may represent an important new treatment option in malignant PEComa, a rare cancer and aggressive form of sarcoma, with no currently approved treatment.

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The content of the publication included the primary analysis, which occurred 6 months after the last patient on the AMPECT study initiated treatment, as well as a 1.5-year follow-up after the primary analysis with a data cutoff of November 23, 2020. In the trial, 34 patients were treated with ABI-009. In the 31 evaluable patients, the overall independently assessed response rate was 39% (12 of 31; with a 95% confidence interval, 22% to 58%) with 1 complete and 11 partial responses. In addition, 52% (16 of 31) of patients had stable disease. The responses were durable and median duration of response was not reached after a median follow-up for response of 2.5 years, and 7 of 12 responders with treatment ongoing (range 5.6-47.2+ months). Responses were of rapid onset (67% by week 6). The safety profile was found to be acceptable with most treatment-related adverse events characterized as low grade and manageable for long-term treatment.

Andrew Wagner, M.D., Ph.D., a senior oncologist at the Dana-Farber Cancer Institute and Principal Investigator of the study, said, "We are excited to publish the data obtained from this trial. nab-Sirolimus delivered highly durable responses in patients with advanced PEComa. Most of the responding patients rapidly achieved a response by their first assessment at 6 weeks following initiation of therapy and these patients have stayed on therapy for extended periods with an acceptable safety profile. We are encouraged by the outcomes in this first-ever prospective clinical trial in patients with this extremely rare disease".

Neil Desai, Ph.D., co-author of the article and Founder, Chief Executive Officer and President of Aadi Bioscience, said, "The Aadi Bioscience team is extremely grateful to the patients, families, and clinical trial teams who help expand the boundaries of available care through their participation in clinical trials. The publication of these results is an important milestone not only for malignant PEComa patients but also for the ongoing development of nab-sirolimus across the planned investigation in TSC1 and TSC2 indications and other combination strategies."

A New Drug Application for investigational ABI-009 is under review by the U.S. Food and Drug Administration for treatment of patients with PEComa and has a Prescription Drug User Fee Action target date of November 26, 2021. If approved, ABI-009 will be known as FYARRO.

On October 22, 2021 Privo Technologies, Inc. ("Privo"), reported the positive results of their Phase 1/2 clinical trial examining their lead asset PRV111 in subjects with early-stage Head and Neck Squamous Cell Carcinoma (HNSCC). PRV111 is an innovative transmucosal delivery system capable of delivering cisplatin topically and directly to the tumor site (Press release, Privo Technologies, OCT 22, 2021, View Source;utm_medium=rss&utm_campaign=privo-technologies-inc-announces-positive-results-from-phase-1-2-clinical-trial-for-prv111-in-head-and-neck-squamous-cell-carcinoma [SID1234591884]). The data from the trial supports the Company’s intended mission since its inception of optimizing state-of-the-art chemotherapeutic drugs to be "Tough on cancer, Easy on patients".

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The primary endpoint of the study, which was to determine a safe and efficacious dose of PRV111 based on the incidence of dose-limiting toxicities (DLTs) and tumor volume changes from baseline, was met. PRV111 was associated with an observable tumor volume reduction of 35-100% (mean 69%). The secondary endpoints were to evaluate tumor responses and evaluate systemic, tumor and lymph node platinum levels following administration of PRV111. The overall tumor response rate in evaluable subjects was 87.5% with an average time to response of 5.5 days. No loco-regional recurrence was observed in 100% of subjects who completed a six-month follow-up. An increase in tumor-infiltrating lymphocytes was present post-treatment.

PRV111 showed a favorable safety profile with no severe adverse events (SAEs). Reported treatment emergent adverse events (TEAEs) were mild or moderate in severity, and no dose-limiting toxicities (DLTs) were observed. PRV111 treatment resulted in cisplatin levels that were found to be >350 times higher in the tumor, >110 times higher in lymph nodes, and >700 times lower in the blood than standard of care cisplatin IV treatments. No reported cases of systemic toxicity were observed.

The clinical trial design was Open-Label, Single-Arm Safety, Tolerability, Anti-Tumor Effects, Systemic Exposure, and Device Technical Effects of PRV111 in subjects with Head and Neck Squamous Cell Carcinoma. This was a two-stage, adaptive, first-in-human pharmacokinetic (PK), safety, and efficacy study. In Stage 1 and Stage 2, a total of 10 enrolled subjects were analyzed for safety and PK; eight of the 10 enrolled subjects were analyzed for efficacy.

Following an End-of-Phase 2 Meeting with the U.S. Food & Drug Administration (FDA), Privo is working on establishing the key elements of a Phase 3 program to support a New Drug Application (NDA) for the treatment of early-stage head and neck squamous cell carcinoma (HNSCC) of the oral cavity.

These clinical trial results have clinically validated the Privo’s transmucosal delivery system, and Privo is now also working to further develop PRV111 platform in a range of mucosal cancers including anal, colorectal, genitourinary, nasal and skin cancers and to explore the use of PRV111 for the treatment of precancerous oral cavity lesions.

About SCC

Squamous cell carcinoma (SCC) is cancer of the squamous cells – thin and flat cells that line the epithelia. SCC is found for the most part as a part of skin cancer, but SCC also accounts for the majority of oral, cervical, vaginal/vulval, and colorectal cancers. SCC in body cavities historically is associated with low survival rates and disfiguring surgeries, demonstrating a clear need for a better treatment. Privo focuses on SCC of the oral cavity as it is on the rise globally and lacks a clear treatment option for such a rare disease. Privo was granted Orphan Drug Designation for Treatment of anatomically accessible oral cancers (lip, tongue, gum, floor of mouth, salivary gland, and other oral cavity) by the U.S. FDA.