On November 12, 2021 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, reported additional clinical data for its tumor infiltrating lymphocyte (TIL) therapy LN-145 in patients with metastatic non-small cell lung cancer (mNSCLC) who enrolled in Cohort 3B of the ongoing basket study IOV-COM-202 (Press release, Iovance Biotherapeutics, NOV 12, 2021, View Source [SID1234595338]). The results are available in a poster at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, November 12-14, 2021, Washington, D.C. and virtual.

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!

The results demonstrate the feasibility of TIL cell therapy in heavily pre-treated patients with NSCLC, and warrant continued investigation of LN-145 as a single-agent and in combination in patients with mNSCLC in ongoing Iovance clinical studies IOV-LUN-202 and IOV-COM-202.

Adam J. Schoenfeld, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center and an investigator in the IOV-COM-202 and IOV-LUN-202 studies, stated, "The clinical data for LN-145 in heavily-treated patients with metastatic non-small cell lung cancer is exciting. It represents the first experience for TIL monotherapy to show clinical benefit in metastatic non-small cell lung cancer and demonstrates the feasibility and safety shown in a multi-center study with a centralized manufacturing process. I am particularly impressed to see responses following multiple prior therapies, including tumors resistant to anti–PD-(L)1 blockade. We observed responses to LN-145 across a range of PD-L1 expression levels, clinical characteristics, and molecular features. I look forward to the ongoing IOV-LUN-202 clinical study in second-line non-small cell lung cancer, where there’s potential to see an increase in overall responses and durability among patients who are earlier in their disease and improve a treatment landscape dominated by chemotherapy."

Following one-time treatment with LN-145 monotherapy, the overall response rate (ORR) is 21.4% in the full analysis set (n=28) and 25% in the efficacy-evaluable set (n=24), including one complete response and five partial responses (August 24, 2021 data cutoff). Two responders, including the CR, had PD-L1 negative tumors and two responders had tumors with KRAS mutations. One complete response and one partial response are ongoing at 20.7 months and 3.0 months, respectively, at a median study follow up of 9.8 months. The treatment-emergent adverse event profile is consistent with the underlying disease and known adverse event profiles of non-myeloablative lymphodepletion and IL-2.

The heavily pre-treated patients in Cohort 3B had received a median of 2 prior therapies. All patients had progressed on prior immune checkpoint inhibitor (ICI) therapy and all six responders received prior chemotherapy. TIL were most commonly grown and manufactured from tumor samples resected from the lung.

Friedrich Graf Finckenstein, M.D., Chief Medical Officer of Iovance, stated, "We are pleased to present our clinical data for LN-145 in metastatic non-small cell lung cancer to the physician community at SITC (Free SITC Whitepaper). There remains a very significant unmet need to increase response rates and prolong survival in the second-line non-small cell lung cancer treatment setting. The data for LN-145 in this signal-finding cohort demonstrated the potential for TIL in metastatic non-small cell lung cancer across a diverse set of patients and informed our ongoing IOV-LUN-202 clinical study in second-line lung cancer. Iovance is committed to advancing both TIL alone and TIL combinations to address multiple non-small cell lung cancer patient populations."

Iovance is currently enrolling patients in the IOV-LUN-202 clinical study to investigate LN-145 in second-line mNSCLC where patients have progressed on prior ICI and chemotherapy. More than 20 clinical sites are currently active in the U.S. and Canada. For more information please visit Iovance.com/clinical or clinicaltrials.gov (identifier NCT04614103).

Iovance Posters and Presentations at SITC (Free SITC Whitepaper) Annual Meeting (November 12-14, 2021)

Title: Phase 2 efficacy and safety of autologous tumor-infiltrating lymphocyte (TIL) cell therapy in combination with pembrolizumab in immune checkpoint inhibitor-naïve patients with advanced cancers
Authors: D O’Malley, et al.
Presentation Type: Oral Presentation
Date and Time: Saturday, November 13, 2021 at 4:30 p.m. ET
Abstract ID: 492

Title: First phase 2 results of autologous tumor-infiltrating lymphocyte (TIL; LN-145) monotherapy in patients with advanced, immune checkpoint inhibitor-treated, non-small cell lung cancer (NSCLC)
Authors: A Schoenfeld, et al.
Presentation Type: Poster (available online)
Abstract ID: 458

Title: Successful generation of tumor-infiltrating lymphocyte (TIL) product from renal cell carcinoma (RCC) tumors for adoptive cell therapy
Authors: B Halbert, et al.
Presentation Type: Poster (available online)
Abstract ID: 176

Title: Expansion of tumor-infiltrating lymphocytes (TIL) using static bag for the clinical manufacturing rapid expansion protocol (REP) process
Authors: K Onimus, et al.
Presentation Type: Poster (available online)
Abstract ID: 101

Conference Call and Webcast on Saturday, November 13, 2021 at 5:30 p.m. ET

Iovance will host a webcast and conference call on Saturday, November 13, at 5:30 p.m. ET to discuss SITC (Free SITC Whitepaper) clinical data updates for Iovance TIL in relapsed, refractory lung cancer as well as Iovance TIL in combination with pembrolizumab in patients with advanced cancers.

Iovance senior leadership will be joined by the following key opinion leaders and principal investigators in Iovance clinical studies:

Omid Hamid, M.D., Chief of Research/ImmunoOncology, The Angeles Clinic and Research Institute; Co-Director, Cutaneous Malignancy Program, Cedars Sinai CANCER
David M. O’Malley, M.D., Professor of Obstetrics and Gynecology at The Ohio State University College of Medicine; Director of the Division of Gynecologic Oncology, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James)
Adam J. Schoenfeld, M.D., Medical Oncologist, Memorial Sloan Kettering Cancer Center
The conference call dial-in numbers are 1-844-646-4465 (domestic) or 1-615-247-0257 (international) and the access code is 3263399. The live webcast can be accessed in the Investors section of the company’s website at www.iovance.com. The archived webcast will be available for one year following the event.

On November 12, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported results from an immunologic analysis of Phase 2 study data showing that trilaciclib enhances both CD4 and CD8 T cell function in certain patients with metastatic triple negative breast cancer (mTNBC) when administered prior to chemotherapy (Press release, G1 Therapeutics, NOV 12, 2021, View Source [SID1234595337]). Patients receiving placebo prior to chemotherapy did not demonstrate enhanced T cell function . Results of the immunologic analysis are being presented in a poster session at the 36th Annual Meeting of The Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), Nov. 10-14, 2021. The poster is available in the scientific publications section of the G1’s website.

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!

"The Phase 2 immunologic data analysis suggests that administering trilaciclib prior to chemotherapy may enhance antitumor efficacy by modulating the composition and response of immune cell subsets," said John Yi, PhD, Director of Translational Medicine at G1 Therapeutics.

In the exploratory analysis, researchers sought to investigate the immune mechanisms underlying the improved rate of overall survival shown in the 2020 Phase 2 trial of TNBC patients receiving trilaciclib in combination with gemcitabine/carboplatin (GCb) compared with GCb alone. The researchers evaluated tumor samples and peripheral blood samples from patients at baseline and after trilaciclib/GCb administration or after placebo/GCb administration to identify differential gene expression and changes in immune function between the two groups. Further, they measured qualitative and quantitative differences between patients who did respond or did not respond to trilaciclib plus GCb. Response to treatment was defined as partial or complete response, while nonresponse was defined as stable or progressive disease.

Among the findings in the poster titled, "Immune Profiling to Investigate Improved Survival in Patients with Metastatic Triple-Negative Breast Cancer Receiving Trilaciclib Prior to Chemotherapy":

Patients who received trilaciclib prior to GCb showed increased T cell function as measured by greater production of inflammatory cytokines
Patients who received trilaciclib had fewer immune suppressing cells known as myeloid-derived suppressor cells (MDSCs) than patients who received GCb alone, whether they were responders or non-responders to treatment
Non-responders to trilaciclib/GCb had a reduction in circulating CD4 and CD8 T cells and a decreased production of inflammatory cytokines
"It is critical that we fully understand the underlying immune mechanisms that contributed to the overall survival improvement that was seen in the Phase 2 mTNBC trials, and to identify biomarkers that will clearly distinguish between trilaciclib responders and non-responders," said Dr. Yi. "We are further investigating the impact of trilaciclib on changes to the tumor-infiltrating immune response in our Phase 3 PRESERVE 2 trial in patients with mTNBC and in a planned mechanism-of-action trial in the neoadjuvant TNBC setting."

About Triple Negative Breast Cancer (TNBC)
According to the American Cancer Society, nearly 300,000 new cases of invasive breast cancer are diagnosed annually in the U.S. Triple-negative breast cancer makes up approximately 15% to 20% of such diagnosed breast cancers. TNBC is cancer that tests negative for estrogen receptors, progesterone receptors, and excess HER2 protein. Because TNBC cells lack key growth-signaling receptors, patients do not respond well to medications that block estrogen, progesterone, or HER2 receptors. Instead, treating TNBC typically involves chemotherapy, radiation, and surgery. TNBC is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. In general, survival rates tend to be lower with TNBC compared to other forms of breast cancer, and TNBC is also more likely than some other types of breast cancer to return after it has been treated, especially in the first few years after treatment. It also tends to be higher grade than other types of breast cancer.

On November 12, 2021 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported updated results from its Phase 1/1b clinical trial of mupadolimab (formerly CPI-006), a humanized monoclonal antibody directed against CD73 with a proposed unique mechanism of activating B cells to generate immune responses to tumor antigens and viruses, and inhibiting the production of immunosuppressive adenosine in the tumor microenvironment (Press release, Corvus Pharmaceuticals, NOV 12, 2021, View Source [SID1234595334]). The clinical data, along with pre-clinical data, further strengthen mupadolimab’s mechanism of action and demonstrate its potential anti-tumor activity in cancer patients.

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!

The data were made available today in an on-demand, electronic poster format for registered participants of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, which is taking place from November 10 to 14, 2021. The poster is also being presented in-person at SITC (Free SITC Whitepaper) by Jason J. Luke, M.D., principal investigator of the trial and Director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center and Associate Professor of Medicine at the University of Pittsburgh School of Medicine.

"We continue to broaden our understanding of mupadolimab’s unique characteristics as an anti-CD73 antibody that exhibits potent blockade of adenosine production as well as powerful adenosine-independent effects on the immune system that result in enhanced B cell and T cell function," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "Recent research has demonstrated that B cells have a vital role in the immune response to tumors from non-small cell lung cancer (NSCLC) and head and neck squamous cell cancers (HNSCC) each frequently containing high numbers of B cells in the tumor and tumor microenvironment. In our Phase 1/1b clinical trial, treatment with mupadolimab in these cancers resulted in tumor regression in patients that failed to respond to, and progressed through prior treatment with anti-PD(L)-1 therapy. This suggests that, in some patients, mupadolimab’s novel mechanism of action may overcome resistance to anti-PD(L)1 therapies."

Dr. Miller added, "In addition, the results presented at SITC (Free SITC Whitepaper) provide important data on the immunologic effects of mupadolimab, as well as pharmacokinetic, pharmacodynamic and safety data for monotherapy and combination therapy. Looking forward, we are now enrolling additional patients with HNSCC and NSCLC in expansion cohorts. These patients will receive the combination of mupadolimab and pembrolizumab and we anticipate reporting results from these expansion cohorts in early 2022. We believe that the data presented at SITC (Free SITC Whitepaper) and data obtained from ongoing expansion cohorts may provide the rationale for a randomized controlled study of mupadolimab, which we expect could begin in 2022."

Mupadolimab Phase 1/1b Clinical Trial Key Results Presented at SITC (Free SITC Whitepaper) 2021
Mupadolimab is being studied in a Phase 1/1b clinical trial in patients with a variety of advanced, refractory cancers, including NSCLC and HNSCC that have failed previous treatment with anti-PD-1 therapy and chemotherapy. The study design included mupadolimab dose escalation from 1 mg/kg to 24 mg/kg intravenous infusion every 3 weeks until disease progression or dose limiting toxicities were reached. Cohorts of patients were treated with mupadolimab monotherapy; combination with ciforadenant, Corvus’ small molecule inhibitor of the A2A receptor; combination with pembrolizumab; or triplet combination with ciforadenant and pembrolizumab.

The data presented at SITC (Free SITC Whitepaper) showed that mupadolimab doses of 12mg/kg are optimal, resulting in complete occupancy of the CD73 target and maximal effects on B cell activation. In the assessment of anti- tumor activity in patients receiving optimal doses of mupadolimab, tumor regression (not meeting the threshold for partial response by RECIST) was seen in five patients who had progressive disease as best response to most recent therapy, which included anti-PD(L)1 therapy (see waterfall plot below). This indicates that tumor regression could occur in patients with tumors refractory to anti-PD(L)1 that are treated with mupadolimab.

A figure accompanying this announcement is available at View Source

"The findings of tumor regression with mupadolimab in patients who had grown through their most recent prior therapy with an anti-PD(L)1 is noteworthy. This supports the possibility that mupadolimab’s mechanism of action could serve to add to effectiveness or overcome limitations of current anti-PD(L)1 therapies. This activity would be expected to be more impactful in patients treated earlier in their disease, with less prior therapies," said Dr. Luke. "We look forward to expanding our experience with mupadolimab in combination with anti-PD(L)-1 in earlier lines of therapy."

Additional mupadolimab oncology program highlights from the SITC (Free SITC Whitepaper) poster presentation include:

Pharmacokinetic (PK) and pharmacodynamic (PD) results showed complete CD73 target occupancy with mupadolimab at doses of 12 mg/kg and higher. Doses up to 18 mg/kg were tolerated without dose limiting toxicities.
Within 30 minutes of mupadolimab intravenous infusion, a reduction in B cells in blood was seen, consistent with redistribution of B cells to lymphoid tissues.
Corvus presented updated preclinical data characterizing mupadolimab’s dual mechanism of action: Mupadolimab is an IgG1 humanized antibody that has been engineered to be Fc gamma receptor binding deficient. Lab data demonstrated that it completely blocks adenosine production from AMP without a hook effect, which is a reduction in binding with higher concentrations of antibody that may limit efficacy to a narrow range of concentrations. In vitro studies showed that binding of mupadolimab to B cells stimulates activation and differentiation into plasmablasts (antibody producing cells) in a mechanism that is independent of adenosine. In vitro studies showed that T cell functions are inhibited by adenosine monophosphate (AMP) and restored by the addition of mupadolimab.
Corvus analyzed CD73 expression in tumor biopsies, obtained from outside sources, using immunohistochemistry from 75 patients with NSCLC and 31 patients with HNSCC. High CD73 expression was seen in tumor cells and/or stroma in all patients. In HNSCC, CD73 expression is predominantly stromal.
Corvus is also developing mupadolimab as a therapeutic for infectious disease, starting with COVID-19. Preclinical data with humanized mice (mice with human immune system) inoculated with SARS-CoV-2 and influenza viral antigens showed that treatment with mupadolimab enhanced antibody responses that were viral specific, demonstrating its potential to be a universal therapy or adjuvant for viral diseases. In September, Corvus announced results from its Phase 3 clinical trial of mupadolimab for COVID-19, which have been published online at medRxiv.org. The results, which cover 40 patients that were enrolled in the trial prior to its voluntary discontinuation, suggest improvement in the primary and key secondary endpoints in patients treated with single doses of mupadolimab at 2mg/kg and 1mg/kg compared to placebo. Due to the small sample size, the results did not reach statistical significance. No drug related adverse events were reported in the trial.

Conference Call, Webcast and Presentation Slides
Corvus will host a conference call and webcast today, November 12, 2021, at 9:00 a.m. ET (6:00 a.m. PT), to discuss the update on mupadolimab and other topics. The conference call can be accessed by dialing 1-877-407-0784 (toll-free domestic) or 1-201-689-8560 (international) and using the conference ID 13724618. The live webcast, which will include presentation slides, may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.

On November 12, 2021 Greenwich LifeSciences Presented the Corporate Presentation (Presentation, Greenwich LifeSciences, NOV 12, 2021, View Source [SID1234595326]).

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!

On November 12, 2021 Anaveon, a clinical stage, immuno-oncology company, reported that it will present a poster on its lead program ANV419 at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting being held from Wednesday, November 10, 2021 to Sunday, November 14, 2021 (Press release, Anaveon, NOV 12, 2021, View Source [SID1234595325]).

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!

Non-Human Primate (NHP) data presented demonstrate that ANV419 has excellent safety and tolerability and selectively proliferates CD8 T cells and natural killer cells. Despite rapid intravenous injection over 1 minute, there were no signs of vascular leak syndrome, cytokine release syndrome or eosinophilia that are normally associated with recombinant IL-2 (aldesleukin) treatment up to the highest treated dose, with the highest dose of 0.3mg/kg considered the No Observed Adverse Effect Level (NOAEL). This favorable pharmacokinetic (PK)/pharmacodynamic (PD) and safety profile of ANV419 in NHPs supports a clinical dosing interval of every two weeks or greater at therapeutically relevant doses.

Based on the safety and the strong pharmacodynamic effects demonstrated in NHPs, Anaveon is conducting a Phase I ascending dose study of ANV419 monotherapy in patients with advanced solid tumors to determine safety and identify a Recommended Phase II Dose (RP2D) for ANV419 treatment. Early clinical data of ANV419 are consistent with the NHP results and suggest an attractive safety/PD relationship, warranting further development in patients with malignant tumors. ANV419, a powerful and selective interleukin-2 (IL-2) agonist, has been designed to overcome known challenges with tolerability and selectivity of recombinant human IL-2.

The abstract is available on the SITC (Free SITC Whitepaper) website and the accompanying poster will be on display on the SITC (Free SITC Whitepaper) 2021 virtual meeting platform and also available on Anaveon’s website.

"We are highly encouraged by the data presented at SITC (Free SITC Whitepaper)," said Christoph Huber, Chief Scientific Officer of Anaveon. "ANV149 has shown a class leading safety profile and we look forward to presenting the first clinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting in April 2022 and to exploring the drug’s efficacy in a range of cancer indications, as well as in combination with other therapeutics."

Details of the poster presentation:

Title: Favorable pre-clinical safety profile of the novel not-alpha IL-2 agonist ANV419 supports first in human clinical development

Poster Presentation: Poster #703 – The ePoster will be on display on the SITC (Free SITC Whitepaper) 2021 virtual meeting platform from 7:00 am ET on Friday, November 12, 2021 and will be presented on both Friday, November 12, 2021 and Saturday November 13, 2021 between 7.00 am and 8.30 am ET.

Anaveon was founded in December 2017. The Company is developing selective IL-2 Receptor Agonists, which have the potential to therapeutically enhance a patient’s immune system to respond to tumors. In the body, human IL-2 stimulates a type of immune cell, called a T-cell, to multiply and become activated. Activated T-cells are able to attack tumors and, consistent with this approach, human IL-2 is already approved as a therapeutic for the treatment of metastatic melanoma and renal cancer; however, due to lack of specificity, human IL-2 has severe, dose-limiting side effects and a short half-life that requires frequent infusions. The lead compound, ANV419, is designed to preferentially signal through the IL-2 beta/gamma receptor and therefore overcome known challenges of human IL-2. This novel type of therapeutic, if approved, could potentially have a wide utility in oncology, including in combination with cell therapies, vaccines, checkpoint inhibitors and radiotherapy.