1stOncology™: Cancer Intelligence Service – Page 5813 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Exelixis Announces Initial Dose-Escalation Results from the First-in-Human Phase 1 Trial Evaluating XL102 in Patients with Advanced Solid Tumors at SABCS 2022

On December 8, 2022 Exelixis, Inc. (Nasdaq: EXEL) reported initial results from the ongoing dose-escalation stage of QUARTZ-101, a phase 1 clinical trial evaluating XL102, a potent, selective, irreversible and orally bioavailable small molecule cyclin-dependent kinase 7 (CDK7) inhibitor, in patients with advanced solid tumors (Press release, Exelixis, DEC 8, 2022, View Source [SID1234624947]). The data are being presented on Thursday, December 8 during the poster session (abstract P4-01-35) at 7:00 a.m. CST at the 2022 San Antonio Breast Cancer Symposium (SABCS).

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!

"Preclinical data for XL102 showed anti-proliferative activity and an ability to induce cell death across various cancer cell lines," said Amita Patnaik, M.D., Co-Director of Clinical Research at the START San Antonio Center for Cancer Care and lead author of the study. "With the initial dose-escalation results now in hand, I am excited to explore further in the QUARTZ-101 trial how XL102 may benefit patients with advanced solid tumors who have exhausted treatment options."

QUARTZ-101 is enrolling patients with solid tumors that are confirmed to be inoperable, locally advanced, metastatic or recurrent. As of the September 7, 2022 data cutoff, 26 enrolled patients had been treated with single-agent oral XL102 at five dose levels: 20 mg once daily (n=3), 40 mg once daily (n=3), 80 mg once daily (n=7), 120 mg once daily (n=4) and 40 mg twice daily (n=9). The most common types of cancer for patients enrolled were hormone receptor-positive breast cancer (n=12), pancreatic cancer (n=3) and sarcoma (n=3). Median age was 63 years. Seventy-three percent of patients had an Eastern Cooperative Oncology Group score of 1, and 77% had received at least three prior lines of systemic anti-cancer therapy for metastatic disease.

"We are pleased to share these data from QUARTZ-101 at SABCS, providing a first look of our novel CDK7 inhibitor in heavily pretreated patients with advanced cancers," said Vicki L. Goodman, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. "As the trial continues, we look forward to learning more about the potential of XL102, alone and in combination, across various cancer types that have strong unmet treatment needs, including metastatic breast cancer."

A pharmacokinetic analysis demonstrated rapid absorption of XL102 with a Tmax of 1-3 hours and an elimination half-life of 5-9 hours. At day 28, AUC0-24 was doubled with the 40 mg twice-daily dose level versus the 40 mg once-daily dose level, supporting twice-daily oral dosing. Target occupancy was exposure-dependent and prolonged relative to XL102 pharmacokinetics, consistent with covalent binding to CDK7.

The median duration of exposure was 9.1 weeks. XL102 was well tolerated at the dose levels evaluated. Dose reductions and dose delays due to a treatment-emergent adverse event (TEAE) occurred in 8% and 35% of patients, respectively; rates were highest with the 80 mg once-daily dose. The most common reasons for discontinuation were radiographic progression (42%), adverse events (12%), lack of clinical benefit (8%) and patient request (8%).

The most common TEAEs of any grade were diarrhea (42%), nausea (38%), fatigue (35%), anemia (27%) and vomiting (23%). TEAEs were generally grade 1 or 2. In the cohort of patients receiving the 40 mg twice-daily dose, one patient experienced dose-limiting toxicity (grade 4 alanine aminotransferase and grade 3 aspartate aminotransferase elevations), which was reversible and led to full recovery. Other grade 3 TEAEs were anemia, ascites, blood alkaline phosphatase increased, fatigue, gastric varices, hyperkalemia, hypertension and hypokalemia. There were no grade 5 treatment-related adverse events. The maximum tolerated dose and recommended phase 2 dose have not yet been determined.

As of data cutoff, no objective responses had been observed. Two patients with stable disease remain on study treatment as of the data cutoff: one with breast cancer and one with liposarcoma, with treatment durations of 46 and 45 weeks, respectively. One additional patient with breast cancer achieved durable stable disease as the best response and discontinued study treatment at 25 weeks. The efficacy of XL102 will be further evaluated in additional patients in the single-agent dose-escalation cohorts, in the tumor-specific cohort-expansion stage and in planned combination studies.

About QUARTZ-101

QUARTZ-101 is a phase 1, open-label dose-escalation and cohort-expansion study evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity and effect on biomarkers of XL102 administered alone and in multiple combination regimens in up to 298 patients with advanced solid tumors. The study includes patients with advanced solid tumors for whom either life-prolonging therapies do not exist or available therapies are intolerable or no longer effective. The first phase is a dose-escalation stage to determine the maximum tolerated dose and/or recommended oral dose of XL102 as a single agent and in combination therapy. In the subsequent cohort-expansion stage, XL102 will be evaluated in patients with certain types of ovarian, breast and prostate cancers. The goal of the cohort-expansion stage is to evaluate the anti-tumor activity of XL102, as assessed per the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as well as its safety, tolerability and pharmacokinetic profile.

More information about the trial is available at ClinicalTrials.gov.

About XL102

XL102 is a potent, selective and orally bioavailable small molecule CDK7 inhibitor, which is an important regulator of the cellular transcriptional and cell cycle machinery. CDK7 helps regulate cell cycle progression, with overexpression observed in multiple cancers, such as breast, prostate and ovarian cancers. XL102 is currently being developed for advanced or metastatic solid tumors. Preclinical studies demonstrated XL102 has anti-proliferative activity and can induce cell death in multiple cancer cell lines. XL102 was in-licensed as part of a collaboration with Aurigene Discovery Technologies Limited.

Alector Reports Inducement Grants under Nasdaq Listing Rule 5635(c)(4)

On December 8, 2022 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology and innate immuno-oncology, reported that on December 6, 2022, the compensation committee of Alector’s board of directors granted 8 (eight) new employees options to purchase an aggregate of 91,851 shares of the company’s common stock and restricted stock units (RSUs) for an aggregate of 40,961 shares of the company’s common stock (Press release, Alector, DEC 8, 2022, View Source [SID1234624946]). These awards are made under Alector’s 2022 Inducement Equity Incentive Plan (the "Plan").

The stock options each have an exercise price of $9.27 per share, equal to the closing price of Alector’s common stock on December 6, 2022. The stock options each have a ten-year term and vest over a period of four years with one forty-eighth of the shares vesting each month. The RSUs vest over a period of three years with one-twelfth of the shares vesting quarterly.

The above-described awards were each granted as an inducement material to the employees entering into employment with the company in accordance with Nasdaq Listing Rule 5635(c)(4) and were granted pursuant to the terms of the Plan.

Bristol Myers Squibb Announces Dividend Increase

On December 8, 2022 Bristol Myers Squibb (NYSE: BMY) reported that its Board of Directors has declared a quarterly dividend of fifty-seven cents ($0.57) per share on the $.10 par value common stock of the company (Press release, Bristol-Myers Squibb, DEC 8, 2022, View Source [SID1234624941]). The dividend is payable on February 1, 2023 to stockholders of record at the close of business on January 6, 2023.

This quarterly dividend represents a 5.6% increase over last year’s quarterly dividend rate of fifty-four cents ($0.54) per share. At this quarterly dividend rate, subject to the normal quarterly review by the Board of Directors, the annual dividend rate for the fiscal year 2023 is $2.28 per share. This marks the fourteenth consecutive fiscal year that the company has increased its dividend and the 91st consecutive year that the company has paid a dividend.

In addition, the Board of Directors has declared a quarterly dividend of fifty cents ($0.50) per share on the company’s $2.00 convertible preferred stock, payable on March 1, 2023 to stockholders of record at the close of business on January 31, 2023.

Delcath Systems Announces Private Placement of $6.2 Million

On December 8, 2022 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of primary and metastatic cancers of the liver, reported that it has entered into a securities purchase agreement with certain accredited investors for a private placement transaction (the "Private Placement") (Press release, Delcath Systems, DEC 8, 2022, View Source [SID1234624939]).

Delcath Systems, Inc. is an interventional oncology company focused on the treatment of primary and metastatic liver cancers.

Delcath will issue and sell 1,448,889 shares of its common stock (the "Common Stock") at a price per share of $2.90, or, in lieu of shares of Common Stock, 692,042 pre-funded warrants to purchase Common Stock (the "Pre-Funded Warrants") at a price per Pre-Funded Warrant of $2.89. The Pre-Funded Warrants will have an exercise price of $0.01 per share of Common Stock, be immediately exercisable and remain exercisable until exercised in full.

Delcath expects to receive gross proceeds from the Private Placement of approximately $6.2 million before deducting offering expenses payable by Delcath.

Delcath intends to use the net proceeds from the Private Placement for working capital purposes and other general corporate purposes.

The closing of the Private Placement is subject to the satisfaction of customary closing conditions.

The securities to be sold in the Private Placement, including the shares of common stock underlying the Pre-Funded Warrants, have not been registered under the Securities Act of 1933, as amended, or state securities laws as of the time of issuance and may not be offered or sold in the United States absent registration with the Securities and Exchange Commission ("SEC") or an applicable exemption from such registration requirements. Delcath has agreed to file one or more registration statements with the SEC registering the resale of the Common Stock and the shares issuable upon exercise of the Pre-Funded Warrants purchased in the Private Placement.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

Dantari Debuts With $47 Million Series A To Advance Best-In-Class Targeted Medicines For Solid Tumors

On December 8, 2022 Dantari, Inc. ("Dantari"), a clinical-stage biotechnology company developing best-in-class targeted therapeutics for the treatment of cancers and other diseases, reported that its emergence from stealth mode with $47 million Series A financing (Press release, Dantari, DEC 8, 2022, View Source [SID1234624938]). The Series A financing was led by Westlake Village BioPartners ("Westlake") and included participation from Corner Ventures, Alexandria Venture Investments, and Caltech. The Company also announced the appointment of Richard A. Markus, M.D., Ph.D., as president and chief executive officer (CEO), and its board of directors, chaired by Sean Harper, M.D., a co-founding managing director at Westlake.

Proceeds from the financing support the advancement of Dantari’s differentiated antibody-drug conjugate (ADC) and chemotherapeutic platforms. Dantari’s platform of T-HDC (Targeted High-capacity Drug Conjugate) technology enables a significantly higher drug-antibody ratio (DAR) and tunable-release of chemotherapy compared to today’s ADCs. The Company’s next-generation targeted therapeutics can deliver larger payloads with a DAR of 60 for greater efficacy, and their biodistribution reduces bone marrow exposure, providing broad therapeutic potential.

The Company’s lead clinical investigational product is DAN-222, a novel HDC chemotherapeutic agent with a topoisomerase 1 inhibitor (topo1) payload. The use of topo1 products is often limited due to bone marrow toxicity. Because of its low bone marrow exposure in preclinical models, DAN-222 has the potential to broaden indications and provide new utility as a combination therapy with PARP inhibitors and other agents. DAN-222 is being evaluated in a Phase 1/2 clinical trial for the treatment of metastatic human epidermal growth factor receptor (HER) 2-negative breast cancer. Early results from the dose-escalation portion of the study will be presented today in a poster session at the 2022 San Antonio Breast Cancer Symposium (SABCS). The study is ongoing and full results will be presented in a future scientific forum.

Dantari’s pipeline also includes several next-generation ADC programs leveraging the T-HDC platform. The Company’s next program, DAN-311 for HER2-positive and HER2-low breast cancer, is planned to enter the clinic in the second half of 2023. Dantari’s other T-HDC product candidates combining validated targets and payloads for a variety of solid tumors including prostate cancer are progressing through preclinical development.

"We are excited to announce Dantari’s launch and initial clinical data. Our vision is to deliver groundbreaking next-generation targeted high-capacity therapeutics with enhanced efficacy and safety," said Dr. Markus. "DAN-222, our lead program in HER2-negative breast cancer, has significant commercial potential while also substantially de-risking our T-HDC platform technology. We look forward to sharing our dose-escalation data today at SABCS which demonstrate excellent translation from preclinical species into patients. We will continue to progress our pipeline as rapidly as possible, including advancing our lead T-HDC candidate DAN-311 in HER2-positive and HER2-low breast cancer into the clinic in 2023. We look forward to bringing much-needed new options to patients who have failed current therapies including traditional ADCs."

Dantari’s HDC and T-HDC platform technology originated at the California Institute of Technology (Caltech) with more than 20 years of research and uses standard organic chemistry manufacturing. Dantari’s T-HDC platform uses chemically defined polymers with a high degree of control and flexibility to optimize performance of targeted drug conjugates and leverages validated targets across a broad range of therapeutic payload options. Payload conjugation enables tunable-controlled release, with no ‘burst release’ and the high drug load enables more payload for greater bystander effect killing of tumor cells including in heterogenous tumors.

Dr. Harper commented, "The Dantari team has made great progress in building a world-class platform for oncology drug innovation. Dantari’s proprietary T-HDC platform provides significantly enhanced capabilities for targeted delivery of therapeutics, which I believe will usher in a step-change in the treatment of solid tumors. With Richard at the helm and this outstanding team, we look forward to the exciting future for this company and the medicines it will advance for patients."

As part of the Series A financing, Mark Davis, Ph.D., Warren and Katherine Schlinger Professor of Chemical Engineering at Caltech, and Pascal Touchon, president and CEO of Atara Biotherapeutics, join Drs. Harper and Markus on the Company’s board of directors.

DAN-222 Phase 1 dose-escalation data at San Antonio Breast Cancer Symposium
Poster Title: A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects with Metastatic Breast Cancer (NCT05261269)
Presenter: Tim Hagerty, Ph.D., vice president of translational sciences, Dantari
Poster ID: OT3-28-01
Session: Ongoing Trials Poster Session 3
Date/Time/Location: Thursday, December 8, 2022; 5:00-6:15 PM CT, Henry B. Gonzalez Convention Center

DAN-222, a novel clinical investigational product, has complementary mechanism of action with PARP inhibitors and can be used in combination since it has demonstrated reduced bone marrow risk in preclinical models. Importantly, the complementary enhanced efficacy is independent of tumor homologous repair deficiency (HRD) status, including BRCA status.

This is an open-label, multicenter, dose-escalation study designed to assess the safety, tolerability, and pharmacokinetics (PK) of intravenously (IV) administered DAN-222 and includes a dose-escalation of DAN-222 in combination with niraparib in patients with HER2-negative metastatic breast cancer.

Results from the first three cohorts showed that the PK profiles of DAN-222 are linear and dose proportional, and that DAN-222 is stable and releasing the payload with consistent kinetics with very low variability between patients (CV% = 7.1 – 20.5). The PK profile of DAN-222 is consistent with and without niraparib.

"These early data on DAN-222 are encouraging as they show this novel platform with high chemotherapy capability appears to be delivering as expected and is well tolerated by patients," said Sara A. Hurvitz, M.D., associate professor at the David Geffen School of Medicine at University of California, Los Angeles (UCLA), medical director of the Jonsson Comprehensive Cancer Center Clinical Research Unit, co-director of the Santa Monica-UCLA Outpatient Oncology Practices, director of the Breast Cancer Clinical Trials Program at UCLA, and clinical consultant and principal investigator of the study.