On June 29, 2022 ADC Therapeutics SA (NYSE: ADCT) reported the first patient has been dosed in LOTIS-7, a Phase 1b clinical trial evaluating ZYNLONTA in combination with other anti-cancer agents in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (Press release, ADC Therapeutics, JUN 29, 2022, View Source [SID1234616379]).

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"As ZYNLONTA has been shown in preclinical studies to have synergistic or additive effects when combined with other anti-cancer therapies, we are eager to explore the potential of our differentiated CD19-directed ADC in combination with other established therapies," said Joseph Camardo, MD, Chief Medical Officer of ADC Therapeutics. "We are excited by the opportunity to allow more lymphoma patients to achieve a response and benefit from the new combinations we are evaluating in LOTIS-7."

The first arm of the LOTIS-7 open-label, multi-center, multi-arm Phase 1b trial will evaluate the safety and activity of ZYNLONTA in combination with polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, high grade B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and Burkitt lymphoma. The trial will include multiple arms in two parts – a dose escalation part and a dose expansion part. For more information about the LOTIS-7 trial, please visit www.clinicaltrials.gov (identifier NCT04970901).

ZYNLONTA is also being evaluated in the LOTIS clinical trial program as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy. For more information about the LOTIS trials, please visit View Source

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death.

The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy.

On June 29, 2022 Molecular Targeting Technologies, Inc. (MTTI), reported that the first patient has been dosed in a clinical trial of EBTATE (177Lu-DOTA-EB-TATE) for the treatment of patients with advanced, well differentiated neuroendocrine tumors. This US based, Phase I clinical trial will evaluate the safety and dosimetry of EBTATE (Press release, Molecular Targeting Technologies, JUN 29, 2022, View Source [SID1234616378]).

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EBTATE is a patented peptide targeting radiotherapeutic drug. It selectively targets and binds to somatostatin receptor 2 on neuroendocrine tumors, which are then killed by the radionuclide. EBTATE was designed to bind to serum albumin, extending in vivo residence time, enabling lower, less frequent dosing of the radiopharmaceutical vs. the current standard of care. Early, ex.-US, clinical results in 60 patients showed EBTATE is more effective and safer for neuroendocrine tumor patients*.

Chris Pak, President & CEO of MTTI comments "This is a substantive milestone for MTTI. It marks the advent of safer, more effective, economical targeted radiotherapy drugs for neuroendocrine tumors. Recent clinical data presented at the 2022 SNMMI meeting also suggests that EBTATE treatment without the conventional amino acids infusion is safe and does no harm to kidney function, potentially, significantly improving patient comfort vs current treatments."

On June 29, 2022 Scorpion Therapeutics, Inc. ("Scorpion Therapeutics"), a pioneering biotechnology company redefining the frontier of precision medicine through its Precision Oncology 2.0 strategy, reported that it has selected STX-721 as a development candidate from its STX-EGFR-EXON20 program (Press release, Scorpion Therapeutics, JUN 29, 2022, View Source [SID1234616377]). STX-721 is a next-generation, orally delivered small molecule designed with potentially best-in-class selectivity to target Exon 20 insertion mutations in epidermal growth factor receptors ("EGFR"), a well-known, clinically validated oncogenic driver in non-small cell lung cancer ("NSCLC").

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NSCLC is the most common form of lung cancer and EGFR mutations are one of the most common mutations in NSCLC. NSCLC tumors that express EGFR with Exon 20 insertion mutations have an incidence of approximately 3,400 patients per year in the United States. Commercially available therapies for NSCLC patients with EGFR Exon 20 insertion mutations have moderate clinical efficacy and are limited by significant toxicities associated with the inhibition of wild-type EGFR in healthy tissues such as the skin and GI tract. These toxicities can lead to dose reductions or interruptions, which may reduce efficacy and leave a significant unmet need.

"We are delighted to announce STX-721 as our second clinical program," said Axel Hoos, M.D., Ph.D., Chief Executive Officer of Scorpion Therapeutics. "While currently marketed agents have transformed the treatment of many EGFR-mutant lung cancers, patients presenting with Exon 20 insertion mutations remain underserved by existing options, which lack sufficient selectivity over wild-type EGFR and therefore carry significant, dose-limiting toxicities that narrow the therapeutic window and attenuate their efficacy. STX-721 was designed as a next-generation molecule to overcome these limitations. We look forward to sharing the detailed preclinical profile for STX-721 later this year and to submitting an IND to the U.S. Food and Drug Administration in 2023."

Leveraging its proprietary drug-hunting platform, Scorpion Therapeutics designed a highly differentiated candidate molecule that provides exquisitely selective inhibition of Exon 20 insertion mutations compared to the wild-type form of the protein. This may allow for maximal inhibition of the mutant protein in cancer cells compared to normal tissues, thereby reducing the toxicities that lead to dose limitations or reductions with existing EGFR Exon 20 inhibitors. In preclinical studies, STX-721 demonstrated best-in-class selectivity versus all other disclosed clinical-phase Exon 20 inhibitors, as well as dose-dependent anti-tumor activity in xenograft models at well-tolerated doses. Scorpion Therapeutics expects to present these preclinical data at a medical meeting in the second half of 2022 and to submit an IND for STX-721 in 2023.

On June 29, 2022 Harbinger Health, a biotechnology company pioneering the detection of early cancer, and Sarah Cannon Research Institute (SCRI) reported the initiation of a 10,000-participant clinical study designed to validate and further develop Harbinger’s novel platform technology for blood-based early cancer detection (Press release, Sarah Cannon Research Institute, JUN 29, 2022, View Source [SID1234616376]).

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The Cancer ORigin Epigenetics- Harbinger Health (CORE-HH) study plans to enroll a diverse and representative population with and without cancer at up to 40 sites across the U.S. The study is being run by SCRI’s contract research organization and has begun enrollment at sites affiliated with HCA Healthcare, SCRI’s parent company.

The primary objectives of the case-control study are to further develop and validate the diagnostic accuracy of Harbinger’s platform technology for the detection of early-stage cancer across multiple cancer types and to assess the ability to determine tumor location. The study, which is expected to read out in stages through 2023, is designed to advance Harbinger’s product development strategy.

"We are pleased to work with SCRI, a leading clinical research organization conducting community-based clinical trials, as we drive toward Harbinger’s goal of enabling the detection of cancer at the earliest points of disease, well before current means of screening could find it and when it’s possible to intervene with the greatest possibilities of success," said Stephen Hahn, MD, CEO of Harbinger Health. "We share a vision of a world where nearly all cancers can be identified before they are symptomatic or even visible with simple, highly accurate and reliable blood tests that are widely accessible, particularly to those who have traditionally been underserved in our healthcare system."

"Improving the ability to detect more cancers at earlier stages is important," said Howard A. "Skip" Burris III, MD, FACP, FACSO, President & Chief Medical Officer, SCRI. "Blood-based testing has emerged in recent years as a potential way to address this important need, and we are excited to partner with Harbinger Health to develop testing capabilities that should improve outcomes for cancer patients through earlier diagnosis."

On June 29, 2022 Avacta Group plc (AIM: AVCT), a clinical stage oncology drug company and developer of powerful diagnostics based on its innovative Affimer and pre|CISION platforms, reported that the first-in-human Phase I trial (ALS-6000-101) of AVA6000 Pro-doxorubicin will advance to the third dose cohort following a positive review of the safety data from the dosing of the second cohort (Press release, Avacta, JUN 29, 2022, View Source [SID1234616375]).

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Avacta’s Safety Data Monitoring Committee (SDMC), comprised of clinicians currently recruiting patients, has completed its review of the safety data from the second cohort dosed with AVA6000 at 120mg/m2 in the ongoing Phase I trial. Following this review, the SDMC has recommended that the clinical trial continues as planned and escalates to the next dose of AVA6000 at 160mg/m2.

AVA6000 is a novel form of doxorubicin that has been modified with Avacta’s pre|CISION FAP-activated delivery platform to improve its safety and therapeutic index. AVA6000 has been designed to limit cell penetration of the drug, and therefore its cell killing effect, until it is specifically activated by fibroblast activation protein α (FAP) which is in high concentration in many solid tumours compared with healthy tissues. The resulting reduced exposure of healthy tissues to active doxorubicin has the potential to significantly increase its therapeutic index by reducing the incidence of adverse effects, including cardiotoxicity and myelosuppression. Anthracyclines such as doxorubicin, a generic chemotherapeutic agent, with a market size that is expected to grow to $1.38bn by 20241, are widely used as part of standard of care in several tumour types, but doxorubicin’s use is limited by cumulative toxicity associated with cardiomyopathy.

Dr Alastair Smith, Chief Executive Officer of Avacta, commented: "AVA6000, and the pre|CISION platform more broadly, have the potential to deliver safer and affordable oncology drugs that could significantly improve cancer patients’ lives. We are very pleased with the progress being made with ALS-6000-101 study and look forward to seeing more data as it emerges from the trial."

Neil Bell, Chief Development Officer of Avacta, commented: "The recommendation from the Safety Data Monitoring Committee to initiate dosing in Cohort 3 with 160mg/m2 of AVA6000 is an endorsement of the emerging safety and tolerability profile in the patients enrolled in this study to date. We look forward to providing additional updates as the dose escalation phase of the trial progresses."