On September 9, 2021 PDS Biotechnology Corporation, a clinical-stage immunotherapy company developing novel cancer therapies based on the Company’s proprietary Versamune T-cell activating technology, reported that it has completed the enrollment of the lead-in safety cohort of its VERSATILE-002 Phase II study evaluating the efficacy and safety of the combination of PDS0101, a clinical stage immunotherapy to treat cancers caused by infection with the human papillomavirus (HPV), and KEYTRUDA (pembrolizumab), a checkpoint inhibitor (CPI) (Press release, PDS Biotechnology, SEP 9, 2021, View Source [SID1234587509]). The combination is being studied for the treatment of advanced human papillomavirus (HPV16)-associated head and neck cancer that has returned or spread. The trial is being conducted in collaboration with Merck & Co.

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The VERSATILE-002 Phase 2 trial is a multi-center, open label, single arm, non-randomized trial that will enroll approximately 100 patients across approximately 25 sites in the U.S. Today the study achieved an important milestone by completing the enrollment of the lead-in safety cohort. Consistent with the study design, further recruitment for the study will commence after a formal analysis by the drug monitoring committee.

VERSATILE-002 is being studied in two groups of HPV16-positive head and neck cancer patients whose cancer has returned or spread. The first group have not been previously treated with a checkpoint inhibitor (CPI naïve). The second group of patients have failed multiple treatments including CPI therapy (CPI refractory).

The advancement of the VERSATILE-002 trial follows the previously disclosed presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting of interim data in a separate Phase 2 trial (NCT04287868) being led by the National Cancer Institute (NCI). That trial is evaluating the combination of PDS0101 with two investigational immunotherapies in patients with advanced HPV-related cancers who have failed prior treatment. Objective responses measured according to RECIST 1.1 (tumor reduction of 30% or more) were reported in 83% (5/6) of HPV16-positive patients who had failed chemotherapy and radiation but were CPI naive. In CPI refractory patients, tumor reduction was reported in 58% (7/12) and objective responses in 42%. Two patients, one in each group were reported to have a complete response (no evidence of disease) at the time of reporting. Current standard of care is reported to result in objective responses of approximately 20% and 10% in CPI naïve and refractory patients respectively. More information on this study can be found on PDS Biotech’s website.

"The early data from these initial studies suggest that Versamune-based immunotherapies administered in combinations that include a checkpoint inhibitor, may have the potential to enhance the immune system’s ability to induce a more powerful and targeted anti-tumor response," commented Dr. Lauren V. Wood, Chief Medical Officer of PDS Biotech. "There is an enormous unmet medical need for more effective treatment of advanced HPV-related cancers and specifically, head and neck cancer. We believe the combination of PDS0101 and KEYTRUDA has the potential to significantly improve clinical outcomes for these patients who have limited treatment options. We look forward to sharing data from this trial as they become available."

Dr. Jared Weiss, Section Chief of Thoracic and Head and Neck Oncology at the University of Carolina at Chapel Hill School of Medicine and Lineberger Comprehensive Cancer Center, is serving as the Lead Principal Investigator of VERSATILE-002. Patients interested in enrolling in this clinical study should email [email protected] or visit the website at View Source to learn more.

On September 9, 2021 Viewpoint Molecular Targeting, Inc., a radiopharmaceutical company developing precision lead-212-based α-particle oncology therapeutics and complementary diagnostic imaging agents, reported that the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug application (IND) to commence a Phase I imaging study of VMT–NET for imaging of neuroendocrine tumors (NETs) (Press release, Viewpoint Molecular Targeting, SEP 9, 2021, https://viewpointmt.com/viewpoint-molecular-targetingtm-receives-fda-clearance-of-investigational-new-drug-application-for-phase-1-imaging-study-for-vmt-a-net-for-neuroendocrine-tumors/ [SID1234587507]). The Phase I imaging study is an investigator-initiated study that will be conducted at the University of Iowa Hospitals and Clinics.

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The Phase I imaging study will evaluate [203Pb]VMT–NET as an agent for imaging somatostatin receptor subtype 2 (SSTR2)-positive neuroendocrine tumors. The images obtained will inform future therapeutic trials of [212Pb]VMT–NET alpha-particle therapy for this tumor type. In parallel to this investigator initiated imaging trial, the Company plans to move forward with a Phase I/IIa therapy study of VMT–NET for the treatment of neuroendocrine tumors.

"We are incredibly pleased that our second product has received IND clearance from the FDA, allowing our collaborators at the University of Iowa to proceed with another first-in-human Phase I imaging study. We continue to be encouraged by the preclinical results demonstrated to date, that show the promise of treating this disease with targeted alpha-particle therapy. With this milestone now achieved, Viewpoint together with the team at the University of Iowa is excited to progress toward enrollment and provisional results in our imaging study over the remainder of this year," commented Frances L. Johnson, MD, Chief Executive Officer and Co-Founder of Viewpoint Molecular Targeting.

Preclinical data seen to-date provides strong evidence that the VMT–NET image-guided approach can be an effective therapy with a promising toxicity profile. Supported by over $4 million in the form of Small Business Innovation Research grants and R01 academic research grants from the NCI to advance this treatment, VMT–NET is well-positioned to apply the new transformative power of alpha-particle treatment to NET tumors and other cancers that express the SST2R biomarker.

Neuroendocrine tumors are rare forms of cancers that occur most commonly in the pancreas or other areas of the gut such as the stomach, small intestine, rectum, colon, or appendix. A neuroendocrine tumor may grow slowly or aggressively and spread to other parts of the body. Diagnosis and treatment of neuroendocrine tumors depend on the type of tumor, its location, whether it produces excess hormones, how aggressive it is and whether it has spread to other parts of the body. Some approaches may include surgery, radiation, and chemotherapy.

On September 9, 2021 Novavax presented Investor Presentation (Presentation, Novavax, SEP 9, 2021, View Source [SID1234587505]).

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On September 9, 2021 Jazz Pharmaceuticals reported that it wasn’t able to ride a breakthrough FDA nod to a pivotal trial win for conditionally approved small cell lung cancer (SCLC) drug Zepzelca (Press release, Jazz Pharmaceuticals, SEP 9, 2021, View Source [SID1234587502]). But after talking with the FDA, the company and partner PharmaMar see a new path forward.

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In previously treated SCLC, the combination of Zepzelca and doxorubicin failed to extend patients’ lives over physician’s choice of doxorubicin-based chemo or Hycamtin, according to data presented at the 2021 World Conference on Lung Cancer virtual meeting.

Jazz and PharmaMar first unveiled the phase 3 ATLANTIS failure in December. Now we know patients who mostly got the Zepzelca regimen as their second-line treatment lived a median 8.6 months, versus 7.6 months in the control arm.

If successful, the trial could have served as the confirmatory trial to convert Zepzelca’s accelerated approval earned last June into a full one. In a previous single-arm study, Zepzelca monotherapy shrunk tumors in 35% of relapsed SCLC patients as measured by investigator assessment. The response lasted a median 5.3 months.

Pascal Besman, chief operating officer at PharmaMar, noted that the ATLANTIS study used a 2-mg/m2 dose of Zepzelca, which is lower than the FDA-approved dose of 3.2-mg/m2. Although the Zepzelca-doxorubicin combo didn’t improve survival, "the overall results support the activity and tolerability of Zepzelca monotherapy in second-line therapy," Besman said in an email interview.

As ATLANTIS investigator Luis Paz-Ares, M.D., Ph.D., noted in a prepared presentation, the research team ran a so-called exposure-response analysis to gauge Zepzelca’s contribution on patient survival. The model predicted that single-agent Zepzelca, at the 3.2-mg/m2 dose, would have had a statistically significant advantage over the control arm at prolonging the lives of patients in the ATLANTIS study.

Jazz stands "firmly behind the favorable benefit/risk profile of monotherapy Zepzelca" in second-line SCLC as shown in its phase 2 trial, the company’s chief medical officer, Rob Iannone, M.D., said in a separate email interview.

For now, Zepzelca will remain on the market. Jazz and PharmaMar have agreed "in principle" with the FDA to run another phase 3 as the confirmatory trial, Besman said.

The three-arm trial will test Zepzelca monotherapy at 3.2 mg/m2, and a second experimental arm will combine the drug at 2 mg/m2 with Pfizer’s Camptosar (irinotecan).

Second-line patients in the control arm will get physician’s choice or either Camptosar or Hycamtin. The trial, expected to launch this year, will also support a regulatory filing to the European Medicines Agency, Besman added.

In addition, Jazz is collecting data from an observational phase 4 trial to understand Zepzelca’s real-world profile in second-line SCLC, Iannone noted.

Meanwhile, Jazz is also looking to move Zepzelca earlier in the treatment line. Through a partnership with Roche, a phase 3 trial dubbed ImForte will test Zepzelca with immunotherapy as a first-line maintenance therapy for patients with extensive-stage SCLC after induction chemotherapy. If successful, the new regimen could pressure AstraZeneca and its Imfinzi, which is currently dominating the front-line SCLC space.

On September 8, 2021 Diaccurate, a French biotech company that develops sole-in-class drug candidates in oncology and immunotherapy, reported the exclusive worldwide in-licensing of the dual targeted PAM inhibitor, formerly M2698, now DIACC3010, from Merck KGaA, Darmstadt, Germany, thus, transforming Diaccurate into a clinical-stage company (Press release, Merck KGaA, SEP 9, 2021, View Source [SID1234587501]).

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DIACC3010 is an oral small molecule inhibitor of the PAM pathway*, one of the most frequently dysregulated molecular circuits involved in cancer progression and resistance to therapies). By acting simultaneously on two key steps of the pathway – AKT1/3 and p70S6 – DIACC3010 is expected to result in a more favorable efficacy and safety profile when compared to other PAM inhibitors. Pre-clinical and Phase I studies have demonstrated that DIACC3010 crosses the blood-brain barrier, a physical frontier that protects the brain from numerous threats but also prevents most drugs from reaching it.

Merck KGaA, Darmstadt, Germany, has completed a multi-institutional Phase I trial led by Apostolia-Maria Tsimberidou, M.D., Ph.D., professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. The study evaluated the safety and efficacy of DIACC3010 as monotherapy in patients with advanced, refractory solid tumors who failed standard therapies, or as combination therapy with trastuzumab and/or tamoxifen in patients with advanced breast cancer**. DIACC3010 was well tolerated as monotherapy. Combined with trastuzumab or tamoxifen, DIACC3010 demonstrated early signs of antitumor activity in patients with advanced breast cancer resistant to multiple standard therapies. Potential biomarkers of DIACC3010 pharmacological activity were seen in peripheral blood mononuclear cells and tumor tissues. Diaccurate will continue to characterize this potential sole-in-class asset in Proof-of-Concept (PoC) Phase II clinical trials in solid tumors enriched with PAM mutations and aggressive lymphomas to be initiated by H2 2022.

"We are confident that Diaccurate’s strong scientific background in developing novel mechanisms makes them the right partner to advance the development of M2698 in cancers with high unmet needs," said Andreas Stickler, Chief Financial Officer and Head of Strategy, Business Development and Portfolio Management of the Healthcare business sector of Merck, KGaA, Darmstadt, Germany.

"We are very proud that, after a highly competitive selection process, Merck KGaA, Darmstadt, Germany, has chosen Diaccurate to bring DIACC3010 into advanced clinical development", said Dominique Bridon, Ph.D., CEO of Diaccurate. "This dual PAM inhibitor could overcome limitations of existing anti-cancer treatments, and, if successful, would be a breakthrough innovation providing hope to patients with high unmet medical needs."

As part of its plan to develop DIACC3010, Diaccurate has designed an extensive PoC clinical program exploring both incurable solid tumors and refractory hemato-oncology indications. The solid tumor component of the program will first focus on cancers associated with a high-prevalence of PAM mutations: Triple Negative Breast Cancer and Gastric Cancer. The hemato-oncology program will address cancers in which the PI3K pathway plays a major role: relapsed/refractory B-cell and T-cell lymphomas. Both Phase II trials are scheduled to be initiated in H2 2022. Further details on the clinical program will be provided in due time.

"Diaccurate is laying the foundations of a successful modern biotech company with a new highly specialized portfolio approach. This is an exciting agreement that will take the Company to the next level, bringing the best of medical science innovation to patients", concluded Philippe Pouletty, M.D., Co-founder & Chairman of Diaccurate, Co-founder & CEO of Truffle Capital.