On October 26, 2022 Exelixis, Inc. (Nasdaq: EXEL) reported promising initial results from the ongoing dose-escalation stage of JEWEL-101, a phase 1 study evaluating XB002, Exelixis’ next-generation tissue factor-targeting antibody-drug conjugate (Press release, Exelixis, OCT 26, 2022, View Source [SID1234622393]). The data are being presented on Friday, October 28 during the Antibody-drug Conjugates Poster Session (abstract 256) at 10:00 a.m. CEST at the 34th Symposium on Molecular Targets and Cancer Therapeutics hosted by the European Organisation for Research and Treatment of Cancer (EORTC), the National Cancer Institute (NCI) and the American Association for Cancer Research (AACR) (Free AACR Whitepaper).

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"Following promising preclinical data, it is encouraging to see that XB002 was well-tolerated across multiple dose levels with a pharmacokinetic analysis supporting the ability of XB002 to remain stable after infusion and reach its target before releasing its cytotoxic payload," said Susanna Ulahannan, M.D., M.Med., Assistant Professor of Medicine in the Section of Hematology/Oncology, University of Oklahoma College of Medicine and Associate Director of Oklahoma TSET Phase 1 Program, OU Health Stephenson Cancer Center at the OU Health Sciences Center. "As the dose-escalation phase progresses, and we initiate enrollment into tumor specific cohorts, I look forward to learning more about how XB002 may benefit people with advanced solid tumors, in particular in tumor types with high unmet need."

JEWEL-101 is enrolling patients with advanced solid tumors for which therapies are unavailable, ineffective or intolerable. A total of 19 patients were enrolled across five initial escalating doses: 0.16 mg/kg (n=3), 0.5 mg/kg (n=3), 1.0 mg/kg (n=6), 1.5 mg/kg (n=3) and 2.0 mg/kg (n=4). The most common types of cancer for patients enrolled were pancreatic cancer, colorectal cancer, cervical cancer and prostate cancer. Median age was 63 years, and 63% of patients had an Eastern Cooperative Oncology Group score of 1. Seventy-nine percent of patients had at least three prior lines of therapy.

"We are pleased to present the first clinical profile of XB002 at ENA 2022, representing an important milestone for our first biologic in clinical development," said Vicki L. Goodman, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. "We are eager to proceed to the expansion cohort stage of JEWEL-101 once the recommended dose is determined, as we aim to further understand the activity of this molecule as a potential new treatment for people who have difficult-to-treat tumors with limited treatment options."

The recommended dose and maximum tolerated dose for XB002 have not yet been determined. As of the data cutoff, there were no dose-limiting toxicities. The primary reasons for treatment discontinuation included radiographic progression (47%), treatment-emergent adverse events (AEs; 11%), lack of clinical benefit (11%) and patient request other than AEs (16%).

A pharmacokinetic analysis demonstrated that XB002 exposure increased more than or proportionately to a dose increase from 0.16 mg/kg to 2.0 mg/kg. XB002 total antibody and intact antibody-drug conjugate pharmacokinetics were similar, suggesting XB002 is stable after infusion. Levels of free payload remained low (<1 ng/mL) at all dose levels. At 2.0 mg/kg, mean AUC0-t was 121 μg∙day/mL for intact antibody-drug conjugate and 4.21 ng∙day/mL for free payload; mean Cmax was 46.6 μg/mL and 0.809 ng/mL, respectively.

Grade 3 treatment-emergent AEs were experienced by 42% of patients; there were no grade 4 or 5 treatment-emergent AEs. Treatment-related AEs were experienced by 63% of patients; all were grade 2 or lower, except for one grade 3 event (hypertension), and improved or resolved prior to the next XB002 dose. Serious AEs were experienced by 16% of patients, and all were considered unrelated to XB002; two patients had grade 3 events (COVID-19 pneumonia and diarrhea), and one patient had grade 2 bacteremia. No bleeding events occurred despite the use of anticoagulant agents in 8 patients (42%).

Ocular treatment-emergent AEs were experienced by 42% of patients, with noninfective conjunctivitis (26%) and dry eye (16%) considered related to XB002 treatment. Incidence of ocular events was higher at the 2 mg/kg dose level (75%) than at the other dose levels (33%). No corneal toxicity was observed. All ocular events were reversible with supportive care, which included lubricating, vasoconstrictive, corticosteroid and/or antibiotic eyedrops.

No objective responses were observed. Three patients with stable disease remain on treatment with XB002: one each with metastatic castration-resistant prostate cancer, appendiceal adenocarcinoma and pancreatic adenocarcinoma, at treatment durations of 42 weeks, 10 weeks and 7 weeks, respectively. One additional patient with uterine carcinosarcoma who achieved stable disease as the best response discontinued XB002 at 15 weeks. In the upcoming cohort-expansion stage, the efficacy of XB002 will be further evaluated as a single agent and in combination with nivolumab.

About JEWEL-101

JEWEL-101 is an open-label, multicenter, first-in-human phase 1 study of Exelixis’ next-generation antibody-drug conjugate XB002 in patients with advanced solid tumors. The trial plans to enroll approximately 450 patients and is divided into two parts: a dose-escalation stage and an expansion cohort stage. Expansion cohorts are planned for cervical cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, pancreatic cancer and several other cancers.

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

About XB002

XB002 is a next-generation antibody-drug conjugate that targets tissue factor, which is overexpressed in a variety of solid tumors. After binding to tissue factor on tumor cells, XB002 is internalized, and the cytotoxic agent is released, resulting in targeted tumor cell death. XB002 is currently being developed for advanced solid tumors. Preclinical findings demonstrate that XB002 binds tissue factor without affecting the coagulation cascade — a limitation of prior tissue-factor-targeting molecules.

On October 26, 2022 Nykode Therapeutics ASA (OSE: NYKD), a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel immunotherapies, reported the presentation of positive preliminary safety and immunogenicity results from its Phase 1/2a study of VB10.NEO, a proprietary individualized therapeutic DNA cancer vaccine, in patients with locally advanced or metastatic solid tumors (Press release, Nykode Therapeutics, OCT 26, 2022, View Source [SID1234622392]). The data will be presented today at the Neoantigen-Based Therapies Summit in Boston, Massachusetts. Nykode is developing VB10.NEO worldwide in partnership with Genentech, a member of the Roche Group.

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Michael Engsig, Nykode’s Chief Executive Officer, stated: "I am thrilled with these clinical data which confirm our position at the forefront of the fully individualized cancer immunotherapy field. We believe individualized neoantigen-based immunotherapies will transform the treatment of cancer, and we are excited to continue the journey with our partners at Genentech, a global leader in immuno-oncology."

Klaus Edvardsen, Nykode’s Chief Development Officer, stated: "The data presented today show that VB10.NEO induces a broad, strong and long-lasting CD8 T cell response against patient-specific tumors, in addition to being safe and well-tolerated in combination with other anti-cancer treatments. The data continue to substantiate our differentiated platform technology and support its huge potential within individualized cancer treatments. We are happy to have such strong partners as Genentech for continued development."

Summary of Safety Results

41 patients were dosed with VB10.NEO. The data show that VB10.NEO was generally safe and well-tolerated in patients with solid tumors when administered in combination with various anti-cancer treatments. The most common adverse events reported were fatigue (34%) and diarrhea (27%). The observed adverse events are generally consistent with the known safety profiles of checkpoint inhibitors, chemotherapy, as well as other targeted cancer therapies, with no overt signs of add-on toxicity.

Summary of Immunogenicity Results

22 patients were included in the interim analysis. Blood samples were collected at baseline, week 11, 22, 34 and 54, to assess immune response to individual neoepitopes by ELISpot.

A neoantigen-specific immune response was observed in all patients (ranging from 3-20 neoepitopes)
A vaccine-induced T cell response was observed in 95% of patients, inducing expansion of both novel and pre-existing T cells
The responses were broad and the majority of the neoepitopes included in the vaccines were immunogenic
Polyfunctional Th1 CD4 and Tc1 CD8 T cell responses were observed
Ranging from 53% to 100% (or 85% on average) of the neoepitopes induced a CD8 T cell response. Cytotoxic CD8 T cells are known to be important for killing tumor cells
The breadth and magnitude of immune response increased upon multiple vaccinations
Responses to the majority of the neoepitopes were maintained for at least one year
Additional information
More details on the results will be available in a slide presentation in the Investors section of the Company’s website at View Source

About the Phase 1/2a Trial
VB N-01 is an open-label first-in-human Phase 1/2a study to evaluate safety, feasibility and efficacy of multiple dosing with individualized VB10.NEO or VB10.NEO and bempegaldesleukin (NKTR-214) immunotherapy in patients with locally advanced or metastatic melanoma, NSCLC, clear renal cell carcinoma, urothelial cancer or squamous cell carcinoma of head and neck, who did not reach complete responses with current standard of care immune checkpoint blockade. More information is available at clinicaltrials.gov: identifier NCT03548467.

About VB10.NEO
VB10.NEO is a proprietary individualized DNA-based neoantigen vaccine in development for the treatment of locally advanced or metastatic solid tumors under an exclusive, worldwide clinical collaboration with Genentech, a member of the Roche group. The vaccine is designed to be produced on-demand according to the neoantigen profile of an individual patient. Neoantigens are proteins generated by tumor-specific mutations not present in normal tissues and are thus an attractive target for cancer immunotherapy as they may be recognized as foreign by the immune system.

Nykode is currently conducting two clinical studies evaluating VB10.NEO: VB N-01 and VB N-02. VB N-01 is an open-label Phase 1/2a basket study to evaluate the safety and efficacy of multiple dosing with VB10.NEO in patients with locally advanced or metastatic cancer (NCT03548467). VB N-02 is an open-label Phase 1B, dose-escalation study of the safety- and antigen-specific immune responses elicited by VB10.NEO in combination with Roche’s checkpoint inhibitor atezolizumab in patients with locally advanced and metastatic tumors (NCT05018273).

On October 26, 2022 Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, reported the presentation of one-year tumor and renal function outcomes data from its Phase 3 ROMAN trial of avasopasem manganese 90 mg for radiotherapy-induced severe oral mucositis (SOM), as well as topline results from a recently completed meta-analysis of the ROMAN and GT-201 SOM trial results, at the 2022 American Society for Radiation Oncology (ASTRO) Annual Meeting (Press release, Galera Therapeutics, OCT 26, 2022, View Source [SID1234622391]). Final data from its Phase 2 AESOP trial of avasopasem for radiotherapy-induced esophagitis were also presented today in a separate session. In addition, poster presentations during ASTRO highlighted the completed Phase 2 EUSOM trial of avasopasem for SOM in Europe and the ongoing GRECO-1 trial of rucosopasem for non-small cell lung cancer. The presentations and posters are currently available in the ASTRO digital program.

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Highlights from the Phase 3 ROMAN data presented at ASTRO:

After one-year follow-up, patients with locally advanced head and neck cancer treated with avasopasem in combination with the standard-of-care regimen (intensity-modulated radiation therapy (IMRT) + cisplatin) demonstrated comparable tumor outcomes and overall survival to patients in the placebo arm.
Patients treated with avasopasem in combination with IMRT + cisplatin had a 10 percent incidence of chronic kidney disease (CKD) after one year of post treatment follow-up, compared to 20 percent of patients in the placebo arm (p=0.0043). CKD (eGFR <60) is a known toxicity risk with cisplatin for these patients and the results highlight success on a predefined exploratory endpoint of renal function. The prospective exploration of this potential benefit of avasopasem was driven by published preclinical data and a post hoc assessment of patients from the GT-201 trial presented at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
"The ROMAN one-year follow-up data show that avasopasem can protect head and neck cancer patients from severe oral mucositis without affecting the treatment benefit of standard-of-care chemoradiotherapy," said Dr. Carryn Anderson, Clinical Associate Professor of Radiation Oncology at the University of Iowa. "Treatment with avasopasem also significantly reduced the likelihood of patients developing cisplatin-related chronic kidney disease compared to placebo at one-year follow-up, suggesting avasopasem can reduce cisplatin renal toxicities and greatly improve patient quality of life."

In addition to the ROMAN long-term endpoints, a meta-analysis of Galera’s two randomized placebo-controlled trials (ROMAN and GT-201; n=551) was included in Dr. Anderson’s ASTRO presentation; these results reinforced that avasopasem therapy resulted in clinically meaningful reductions in radiotherapy-induced SOM, including a significant reduction in the incidence, duration, onset and severity of SOM compared to placebo.

"The data presented today affirm our belief that avasopasem is providing real benefit for patients with head and neck cancer undergoing the current standard of care," said Mel Sorensen, M.D., Galera’s President and CEO. "We look forward to submitting the NDA to the FDA by the end of 2022 with the intention of bringing avasopasem to patients as the first FDA-approved drug for radiotherapy-induced SOM."

About Severe Oral Mucositis (SOM)

Approximately 42,000 patients with head and neck cancer undergo standard-of-care radiotherapy every year in the U.S. and are at risk of experiencing SOM. In patients with head and neck cancer, radiotherapy is a mainstay of treatment. Approximately 70 percent of patients receiving radiotherapy for head and neck cancer develop SOM, defined by the inability to eat solid food or drink liquids. The impact on patients who develop SOM is substantial, particularly when hospitalization and/or surgical placement of PEG tubes to maintain nutrition and hydration are required. SOM can adversely affect cancer treatment outcomes by causing interruptions in radiotherapy, which may compromise the otherwise good prognosis for tumor control in many of these patients. There is currently no drug approved to prevent or treat SOM for these patients.

About Avasopasem

Avasopasem manganese (avasopasem, or GC4419) is a selective small molecule dismutase mimetic in development for the reduction of radiotherapy-induced severe oral mucositis (SOM) in patients with locally advanced head and neck cancer (HNC) and for the reduction of radiotherapy-induced esophagitis in patients with lung cancer. The FDA has granted Fast Track and Breakthrough Therapy designations to avasopasem for the reduction of SOM induced by radiotherapy, with or without systemic therapy.

On October 26, 2022 Targovax ASA (OSE: TRVX) reported that it will announce its third quarter 2022 results on Thursday 3 November 2022 (Press release, Targovax, OCT 26, 2022, View Source [SID1234622390]). Targovax’s management will present the results at a live streamed webcast at 10:00 am CET to investors, analysts and the press.

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The results report and the presentation will be available at www.targovax.com in the Investors section from 07:00 am CET, on 3 November 2022.

Presentation
There will be a virtual presentation of the results with a live webcast 3 November at 10.00 am CET. You can join the webcast here. It will be possible to ask questions during the presentation

On October 26, 2022 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that it is supporting a Phase 2 investigator initiated study (ISS) of trilaciclib and lurbinectedin in patients with extensive stage small cell lung cancer (ES-SCLC) (Press release, G1 Therapeutics, OCT 26, 2022, View Source [SID1234622389]). An ISS is a study that is proposed, developed, and conducted by a qualified sponsor external to G1 Therapeutics who assumes full responsibility for the conduct of the study.

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Trilaciclib, an IV-administered transient CDK4/6 inhibitor, is a first-in-class therapy designed to preserve bone marrow and immune system function during chemotherapy to improve patient outcomes.

"Pretreatment with trilaciclib may improve the therapeutic potential of lurbinectedin, another important medication for SCLC, in multiple ways," said Jared Weiss, M.D., Professor of Medicine, Division of Oncology, Lineberger Comprehensive Cancer Center at the University of North Carolina Chapel Hill, NC and principal investigator in this study. "Trilaciclib is a proven myeloprotective agent, but studies to date have only assessed it in the context of topotecan-containing and platinum/etoposide-containing chemotherapeutic regimens. Lurbinectedin is effective, but also highly myelosuppressive, which is particularly problematic given recent data that clarify the importance of maintaining adequate exposure for efficacy. The opportunity for immunological synergy with lurbinectedin – which potently suppresses myeloid derived suppressor cells (MDSCs) – is also evident given data that suggest trilaciclib’s ability to induce novel T cell clonality, improve the CD8+ T cell/Treg ratio, and increase antigen expression and presentation."

This is a prospective, non-randomized, single-arm Phase 2 study, to evaluate trilaciclib administered intravenously prior to lurbinectedin in approximately 30 subjects with platinum refractory ES-SCLC. Patients will receive trilaciclib and lurbinectedin on day one of each 21-day cycle until discontinuation or disease progression.

The primary endpoint is the rate of grade 4 neutropenia in any cycle when trilaciclib is administered prior to lurbinectedin in subjects with extensive stage small cell lung cancer (ES-SCLC). Secondary endpoints include mean duration (days) of grade 4 neutropenia in cycle 1, overall survival (OS), progression-free survival (PFS), overall rate of response (ORR), quality of life assessments, and the use of secondary/reactive supportive measures including G-CSF administration.

About Small Cell Lung Cancer
In the United States, about 29,000 cases of small cell lung cancer (SCLC) are diagnosed each year. SCLC, one of the two main types of lung cancer, accounts for about 10% to 15% of all lung cancers. SCLC is an aggressive disease and tends to grow and spread faster than NSCLC. It is usually asymptomatic; once symptoms do appear, it often indicates that the cancer has spread to other parts of the body. About 70% of people with SCLC will have cancer that has metastasized at the time they are diagnosed. The severity of symptoms usually increases with increased cancer growth and spread. From the time of diagnosis, the general 5-year survival rate for people with SCLC is 6%. The five-year survival rates for limited-stage (the cancer is confined to one side of the chest) SCLC is 12% to 15%, and for extensive stage (cancer has spread to the other lung and beyond), survival rates are less than 2%. Chemotherapy is the most common treatment for SCLC.