On May 26, 2022 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing therapies that combine both targeted and immune-mediated mechanisms, reported positive results from its Phase 1 clinical trial of TPST-1120, a first-in-class1 PPARα antagonist, as a single agent and in combination with nivolumab in patients with advanced solid tumors (Press release, Tempest Therapeutics, MAY 26, 2022, View Source [SID1234615104]). The results will be presented in an oral presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, IL, by Mark Yarchoan, M.D., associate professor of oncology at Johns Hopkins School of Medicine.

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Dr. Yarchoan commented, "The anti-cancer activity observed in these late-stage solid tumor patients is encouraging, particularly in light of their treatment history and the difficult nature of the tumor types. Based on the clinical activity observed with monotherapy, and the responses observed with combination therapy in patients with prior progression on checkpoint inhibitor therapy, a tolerable safety profile and distinct mechanism of action, I see significant potential in multiple tumor types and look forward to the ongoing development of TPST-1120."

Sam Whiting, chief medical officer of Tempest, added, "We are excited to see these positive TPST-1120 results in Tempest’s first presentation of clinical data, especially given the advanced stage and treatment histories of these patients. We look forward to presenting these data at ASCO (Free ASCO Whitepaper) and the continued development of TPST-1120 in the ongoing first-line randomized study in patients with hepatocellular carcinoma."

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1 If approved by the FDA

TPST-1120 Monotherapy Results

In the monotherapy portion of the trial, 19 patients with late-line treatment-refractory solid tumors, including pancreatic, cholangiocarcinoma (CCA), and colorectal cancers, were treated with oral twice-daily TPST-1120. The results showed that 53% (10/19) of patients experienced clinical benefit in the form of disease control, including tumor shrinkage in 21% of the patients. Two patients with late-line CCA, an aggressive tumor type and disease setting usually unresponsive to therapy, including IO therapies, achieved durable stable disease and one of the patients achieved durable tumor shrinkage.

TPST-1120 and Nivolumab Combination Therapy Results

In the combination therapy portion of the trial, 15 patients with heavily-pretreated renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and CCA were treated with oral twice-daily TPST-1120 and the anti-PD-1 therapy, nivolumab. All of the HCC and RCC patients had received an approved anti-PD-1 therapy in at least one prior line of therapy and discontinued that treatment due to disease progression. Promising objective responses (RECIST v1.1) were observed in two patients with late-line RCC who had previously progressed on anti-PD-1 therapy without an objective response (ORR 50%, n=2/4, in evaluable RCC patients). A third RECIST response was observed in a patient with late-line, heavily pre-treated CCA, a tumor type generally not responsive to anti-PD-1 alone.

Notably, all three responders were treated at the two highest doses of TPST-1120 (ORR 30%, 3/10).

Safety

TPST-1120 was well tolerated as both a monotherapy and in combination with nivolumab. The majority of the treatment-related adverse events were Grade 1 and 2, and included nausea, fatigue and diarrhea. No dose-limiting toxicities were reported during dose escalation.

ASCO Events

Presentations Details

Title: A phase 1 study of TPST-1120 as a single agent and in combination with nivolumab in subjects with advanced solid tumors

Session Typer/Title: Oral Abstract Session, Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Session Date and Time: Tuesday, June 7, 2022; 9:45 a.m. – 12:45 p.m. CDT
Abstract Number: 3005

Title: A phase 1 study of TPST-1495 as a single agent and in combination with pembrolizumab in subjects with solid tumors

Session Type/Title: Poster Session, Developmental Therapeutics – Immunotherapy
Session Date and Time: Sunday, June 5, 2022; 8:00 a.m. – 11:00 a.m. CDT
Abstract Number: TPST2696

Tempest Investor Event

Tempest will host and webcast an investor event in conjunction with the ASCO (Free ASCO Whitepaper) Annual meeting on Sunday, June 5, 2022 at 6:30 a.m. CDT. Company management will be joined by key thought leaders:

Mark Yarchoan, M.D.
Associate Professor of Oncology
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Susanna V. Ulahannan, M.D., MMEd
Assistant Professor of Medicine
Associate Director, Oklahoma TSET Phase 1 Program
Stephenson Cancer Center at the University of Oklahoma

Jason Luke, M.D.
Associate Professor of Medicine
Director – Immunotherapy and Drug Development Center
UPMC Hillman Cancer Center

Toni K. Choueiri, M.D.
Director, Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute
Jerome and Nancy Kohlberg Chair and Professor of Medicine,
Harvard Medical School

To access the live or archived recording of the investor event, please visit the investor section of the Tempest website at View Source

About TPST-1120

TPST-1120 is a first-in-class2 oral selective PPAR⍺ antagonist with a dual mechanism designed to target both tumor cells directly and suppressive immune cells in the tumor microenvironment. Both types of targeted cells are dependent on fatty acid metabolism, which is regulated by the PPAR⍺ transcription factor. In extensive non-clinical studies, TPST-1120 as a monotherapy and in combination with other anti-cancer drugs resulted in significant reductions in tumor growth and stimulation of durable anti-tumor immunity. In addition to the study being presented at ASCO (Free ASCO Whitepaper), in collaboration with F. Hoffmann La Roche, TPST-1120 is also advancing through a randomized, first-line, global, Phase 1b/2 clinical study in combination with the standard-of-care regimen of atezolizumab and bevacizumab in patients with advanced or metastatic hepatocellular carcinoma.

On May 26, 2022 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported additional exploratory data for poziotinib in non-small cell lung cancer (NSCLC) patients harboring HER2 exon 20 insertion mutations at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held in Chicago from June 3-7 (Press release, Spectrum Pharmaceuticals, MAY 26, 2022, View Source [SID1234615103]).

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In poziotinib treated patients with advanced NSCLC harboring HER2 exon 20 insertion mutations, baseline ctDNA presence was associated with the tumor tissue genotyping with a concordance of 95%. In patients who responded to treatment, reduced ctDNA levels were associated with tumor mass reduction by central imaging. Increases in ctDNA were observed prior to confirmation of tumor escape, or disease progression.

"This early data suggests that a reduction in ctDNA may be a predictor of response to treatment with poziotinib," said Francois Lebel, M.D., Chief Medical Officer of Spectrum Pharmaceuticals. "We are encouraged by these findings and look forward to further investigate ctDNA as a potential predictive biomarker of poziotinib treatment response."

Poziotinib is currently under review by the U.S. Food and Drug Administration (FDA) with a PDUFA date of November 24, 2022 and has received Fast Track designation from the agency.

Session title and information for the poster is listed below and is available on the ASCO (Free ASCO Whitepaper) online itinerary planner.

Circulating tumor DNA (ctDNA) in HER2 exon 20 insertion mutations and responses in NSCLC HER2 exon 20 insertion treated with poziotinib
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Session Date and Time: Sunday, June 5, 2022, 8-11 a.m. CDT, 6-9 a.m. PT
Location: McCormick Place, Chicago IL
Abstract: 3051 / Poster: 43

Copies of the presentation will be available on Spectrum’s website at View Source following presentation at the meeting.

About the ZENITH20 Clinical Trial

The ZENITH20 study is a multicenter, open-label Phase 2 trial, evaluating poziotinib in patients with advanced or metastatic NSCLC patients with EGFR or HER2 exon 20 insertion mutations. The trial is comprised of 7 independent cohorts. Cohorts 1 – 4 were each independently powered for a pre-specified statistical hypothesis with a primary endpoint of ORR, or objective response rate evaluated by independent review committee (RECIST v1.1). Cohorts 5 – 7 are exploratory. Secondary outcome measures are disease control rate, duration of response, progression-free survival, and safety and tolerability. The patients’ quality of life is also measured and assessed throughout. Cohort 4 includes first-line NSCLC patients with HER2 exon 20 mutations and cohort 5 includes previously treated or treatment-naïve NSCLC patients with EGFR or HER2 exon 20 insertion mutations.

About Poziotinib

Poziotinib is a novel, oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that inhibits the tyrosine kinase activity of EGFR as well as HER2 and HER4. Importantly this, in turn, leads to the inhibition of the proliferation of tumor cells that overexpress these receptors. Mutations or overexpression/amplification of EGFR family receptors have been associated with a number of different cancers, including non-small cell lung cancer (NSCLC), breast cancer, and gastric cancer. HER2 exon 20 insertion mutations are a rare subset accounting for approximately 2-4% in NSCLC. There is no approved therapy for either treatment-naïve or previously treated NSCLC with HER2 exon 20 insertion mutations. The company holds an exclusive license from Hanmi Pharmaceutical to develop, manufacture, and commercialize poziotinib worldwide, excluding Korea and China. Poziotinib is currently being investigated by the company and Hanmi in several mid-stage trials in multiple solid tumor indications.

On May 26, 2022 SHINE Technologies, LLC (SHINE), a next-generation nuclear technology company, reported CEO and founder Greg Piefer will give an invited presentation at the Wisconsin Entrepreneurs’ Conference in Milwaukee (Press release, Shine Medical Technologies, MAY 26, 2022, View Source [SID1234615102]). On Thursday, June 2 at 8:45 a.m., Piefer will present the opening keynote before engaging in discussion with the audience.

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Produced by the Wisconsin Technology Council, the Entrepreneurs’ Conference is among the largest events for entrepreneurs and early-stage investors in the Upper Midwest. The theme for the 20th annual conference is "Putting Early Stage Pieces Together." It is one of the Midwest’s premiere hands-on events for entrepreneurs of all ages and experience levels. Attendees range from entrepreneurs who are still developing their ideas to emerging company leaders who have already attracted angel and/or venture funding. These businesses cover a broad span of categories, from information technology to cleantech, from advanced manufacturing to the life sciences, and from business services to consulting.

Piefer will discuss progress at SHINE, headquartered in Janesville, Wis., which raised several hundred million dollars from investors in the last three years alone for its revolutionary, fusion-based technologies. Early applications include production of commonly used medical radioisotopes to diagnose and treat serious illnesses such as heart disease and cancer. 

Piefer holds a Ph.D. in nuclear engineering and related degrees from UW-Madison. A recent speaker at a White House summit on commercial fusion energy, Piefer has received the UW-Madison Early Career award; is the primary inventor on multiple patents; is author or co-author of many publications; and serves on several for-profit and non-profit board of directors.

On May 26, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported top-line clinical data from its Phase 1/2 trial of galinpepimut-S (GPS), the Company’s Wilms Tumor-1 (WT1)-targeting peptide immunotherapeutic, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients diagnosed with WT1(+) relapsed or refractory platinum resistant advanced metastatic ovarian cancer (Press release, Sellas Life Sciences, MAY 26, 2022, View Source [SID1234615101]).

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Data from 15 patients enrolled in the study, conducted under a Clinical Trial Collaboration and Supply Agreement with Merck & Co., Inc., Rahway, N.J., USA (known as MSD outside the United States and Canada), has been preliminarily analyzed with final data for all 17 patients enrolled in the clinical trial expected by the end of 2022. All enrolled patients were resistant to standard of care platinum-based therapy and 78.5 percent of evaluable patients were refractory to or had failed their first- or second-line therapies with 21.5 percent having failed three or more lines of therapy, including one patient who failed five previous lines of therapy. Of the 15 patients, 13 received at least three doses of GPS, the last of which was in combination with pembrolizumab, and were evaluable for response outcomes.

Summary of Top-Line Clinical Data

The overall response rate (ORR) of the trial is (7.7 percent), similar to the response to checkpoint inhibitors.
An ad hoc analysis of clinical outcomes in this cohort shows a disease control rate (DCR), the sum of overall response rate and rate of stable disease, of 53.9 percent at a median follow-up of 43.1 weeks. In a checkpoint inhibitor single agent study in a similar platinum-resistant ovarian cancer patient population treated with a checkpoint inhibitor alone, the observed DCR was 37.2 percent, consistent with a DCR rate increase of 45 percent in the GPS combination with pembrolizumab over that seen for checkpoint inhibitors alone.
Median progression-free survival (PFS) was 12 weeks compared to 8.4 weeks for checkpoint inhibitors alone seen in studies with similar patient populations, a 43 percent increase in the GPS combination with pembrolizumab. Patients with fewer previous lines of chemotherapy experienced a more favorable median PFS than those with more than two previous lines: for patients with two or fewer previous lines of therapy treated with GPS in combination with pembrolizumab, median PFS was 24 weeks.
With 43.1 weeks of follow-up the median overall survival has not been reached.
The safety profile of GPS in combination with pembrolizumab was similar to pembrolizumab alone, with the only addition of low-grade rapidly resolving local reactions at the GPS injection site, consistent with observations from other GPS clinical studies.
"These early data are an example of a new direction in development of immunotherapy for platinum-refractory ovarian cancer," commented Jeffrey S. Weber, M.D., Ph.D.; Deputy Director of the Perlmutter Cancer Center at New York University (NYU)-Langone Health; Co-Director of its Melanoma Research Program Center; and Chair of SELLAS’ Scientific Advisory Board. "In patients who failed as many as five lines of previous therapy, with small numbers of patients, the disease control rate and progression free survival that were observed merit further study. The GPS combination with checkpoint blockade, such as pembrolizumab, should be further explored, both in active disease as well as potentially in the setting of maintenance therapy after patients reach minimal residual disease post salvage therapies," added Dr. Weber.

"GPS has been primarily designed as maintenance therapy in order to provide an overall survival benefit after patients reach the minimal residual disease state or complete remission. However, in this very difficult to treat patient population with active disease, who underwent intensive chemotherapies with no apparent clinical benefit and a severe toxicity toll, the combination of GPS and pembrolizumab seems to be effective in the active disease state by halting or slowing down progression without significant further side effects," said Angelos Stergiou, M.D., Sc.D. h.c., President and CEO, SELLAS.

"As we continue to do further analyses, including immune response and correlative analyses, which will be presented at an upcoming medical conference, we are also considering how to best pursue development of GPS in combination with PD1 inhibitors in this patient population and we are excited about the path ahead. I would like to wholeheartedly thank all patients for participating in the study as well as their physicians, nurses and study teams as well as collectively our teams at SELLAS and Merck," concluded Dr. Stergiou.

About Ovarian Cancer
Ovarian cancer is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women in the United States. Over 22,000 cases are diagnosed annually, and there are an estimated 15,500 deaths per year. The majority of patients have widespread disease at presentation. The 5-year survival for advanced-stage disease remains less than 30 percent. Combining GPS with the checkpoint inhibitor pembrolizumab, which beneficially and profoundly alters the tumor microenvironment (TME) is hypothesized to increase the proportion of patients who develop an immune response against their cancer and potentially improve their clinical outcome over checkpoint inhibitors monotherapy, without the burden of additional toxicities in macroscopically measurable malignancies.

On May 26, 2022 Rubius Therapeutics, Inc. (Nasdaq:RUBY), a clinical-stage biopharmaceutical company that is genetically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics for the treatment of cancer and autoimmune diseases, reported that the Company will present a Trials in Progress poster presentation for its second broad immune stimulation program, RTX-224, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held virtually from June 3-7, 2022 (Press release, Rubius Therapeutics, MAY 26, 2022, View Source [SID1234615100]).

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The Trials in Progress poster presentation will summarize the proposed mechanism of action of RTX-224, preclinical observations to date and the clinical trial design, including the translational medicine approach, for the ongoing Phase 1/2 clinical trial of RTX-224 for the treatment of patients with select advanced solid tumors, including cutaneous melanoma, head and neck squamous cell carcinoma, non-small cell lung cancer, triple negative breast cancer and urothelial cancer.

Poster Title: A Phase 1/2 Study of RTX-224, an Engineered Red Blood Cell Expressing 4-1BB Ligand and Membrane-Bound IL-12, for the Treatment of Patients with Select Advanced Solid Tumors
Session Title: Developmental Therapeutics—Immunotherapy
Abstract Number: TPS2680
Date and Time: Sunday, June 5, 2022, 8:00-11:00 a.m. CDT

About the RTX-224 Phase 1/2 Clinical Trial

This is a Phase 1/2 open label, multicenter, multidose, first-in-human dose-escalation and expansion study to determine the safety and tolerability, pharmacokinetics, maximum tolerated dose and a recommended Phase 2 dose and dosing regimen of RTX-224 in adult patients with certain relapsed/refractory or locally advanced solid tumors including non-small cell lung cancer, cutaneous melanoma, head and neck squamous cell carcinoma, urothelial (bladder) carcinoma and triple-negative breast cancer. The trial will also assess pharmacodynamic changes in immune cell populations relative to baseline and anti-tumor activity. The study will include a monotherapy dose escalation phase followed by an expansion phase in specified tumor types during the Phase 2 portion of the trial.

About RTX-224

RTX-224 is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to express hundreds of thousands of copies of 4-1BB ligand (4-1BBL) and interleukin-12 (IL-12) on the cell surface. RTX-224 is designed to broadly stimulate the immune system by activating and expanding NK and CD8+ memory T cells and is expected to produce a broad and potent anti-tumor T cell response, an innate immune response and generate anti-tumor activity in those tumor types with known sensitivity to T cell killing, including tumor types with high mutational burden, PD-L1 expression and/or known responsiveness to checkpoint inhibitors.