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ImmVira presented latest encouraging clinical results of two proprietary products at ASCO 2023

On June 6, 2023 ImmVira reported four abstracts covering latest results from Phase I/II clinical trials of MVR-T3011 IT (intratumoral injection) and MVR-T3011 IV (intravenous injection) in both U.S. and China with all selected to be published (1 chosen for poster discussion) at the 2023 American Society for Clinical Oncology Annual Meeting (ASCO 2023) taking place from June 2nd to 6th, 2023 in Chicago, IL (Press release, Immvira, JUN 6, 2023, View Source [SID1234632531]).

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1. Intratumoral product MVR-T3011 IT demonstrated clinical efficacy both as monotherapy and combination therapy

1） Phase I/IIa study of MVR-T3011 IT administered via intratumoral injection in China as monotherapy

Being among the 22 China studies selected for Poster Discussions this year, MVR-T3011 IT clinical updates in China was also presented in a Poster discussion session on June 3rd (see below).

As of January 18, 2023, among 90 patients who received MVR-T3011 IT monotherapy, the most frequent treatment-related adverse events ("TRAEs") were pyrexia and no dose-limiting toxicity ("DLT") events were reported. Recommended Phase II dose ("RP2D") was determined to be 1×108 PFU/ml.

The confirmed objective response rate ("ORR") was 11% and disease control rate ("DCR") was 49% in 55 patients (with head and neck squamous cell carcinoma ("HNSCC"), sarcoma, melanoma, breast cancer, etc.) treated under RP2D evaluable for tumor response. 12 evaluable HNSCC patients who progressed after platinum-based chemotherapy and anti-PD-1/PD-L1 therapy achieved confirmed ORR of 25% and DCR of 50%, respectively.

Meanwhile, 69.2% of patients were observed with increases in tumor-infiltrating CD8+ cell density in biopsy collected at 8 weeks after the first dose. In particular, 3 head and neck cancer patients with partial response ("PR") had notable increases in tumor-infiltrating CD8+ cell density in biopsy.

Trial results showed that, MVR-T3011 IT had excellent safety profile and clinical compliance. The drug didn’t spread to blood, urine or saliva when injected intratumorally. Additionally, MVR-T3011 IT monotherapy demonstrated encouraging anti-tumor activity in advanced HNSCC patients, supporting further evaluation in Phase II studies.

2） Phase I/IIa study of MVR-T3011 IT administered via intratumoral injection in the U.S. as monotherapy and combination therapy combined with Pembrolizumab

As of January 17, 2023, among 29 patients who received MVR-T3011 IT monotherapy or in combination with pembrolizumab, most frequent TRAEs were pyrexia, and no additional safety signals were observed in combination therapy.

12 advanced melanoma patients failing prior PD-1 or PD-1/CTLA-4 combination treatment received MVR-T3011 IT monotherapy. The confirmed ORR and DCR were 25.0% and 33.3%, respectively. 6 patients (including 5 with melanoma and 1 with mesothelioma) were re-challenged with MVR-T3011 IT combined with pembrolizumab after progression on monotherapy, among which 1 patient achieved PR after 4 months and ongoing PR had lasted for more than 8 months as of the data cutoff date.

Meanwhile, remarkable increases in tumor-infiltrating CD8+ cell density in biopsy were observed in 66.7% of patients with PR or stable disease ("SD"). In particular, the increment of CD8+ cell density in 2 melanoma patients with PR was over 15 folds.

Trial results showed that, MVR-T3011 IT monotherapy and combination therapy with pembrolizumab were safe and tolerable. MVR-T3011 may modify tumor microenvironment and overcome immune resistance.

2. MVR-T3011 IV, global first intravenous oHSV product, showed assuring safety profile

As of December 16, 2022, a total of 15 patients (including 12 patients who received single ascending dose and 3 patients who received multiple ascending dose) received MVR-T3011 IV monotherapy with different dosages (1×106 PFU~3×108 PFU), all of which were Stage IV patients with chemotherapy history, including 9 patients who had received third-line or above treatment. Among them, 11 patients achieved SD, and the DCR was 73.3%. Notably, one colorectal cancer patient who progressed after irinotecan-based chemotherapy, anti-VEGF, and radiation therapy had long-term disease control with SD for over 4 months.

Among these patients, three had Grade 3 treatment emergent adverse events ("TEAE") in the Common Criteria for the Evaluation of Adverse Events ("CTCAE") (hypertriglyceridemia, dyspnea, lymphopenia), only one case of Grade 3 TRAE (lymphopenia) was reported, and no≥ Grade 4 adverse event ("AE") was reported. No drug-related Serious Adverse Event ("SAE") or DLT occurred; maximum tolerated dose ("MTD") was not reached.

Trial results showed that, MVR-T3011 IV is safe, well-tolerated, and unlikely to spread to close contacts. Encouraging preliminary efficacy and MVR-T3011 viral DNA in blood in a dose-dependent manner with additive effects from repeated doses support continued recruitment of patients to higher dose cohorts.

In the meantime, MVR-T3011 IV’s U.S. Phase I clinical data was also selected to be published at ASCO (Free ASCO Whitepaper) this year. We are expecting to report more intravenous clinical results in both U.S. and China in the future.

About MVR-T3011 IT and MVR-T3011 IV

MVR-T3011 IT and MVR-T3011 IV are two separate products developed on the same basis of MVR-T3011. MVR-T3011 IT is designed for intratumoral injection of solid tumors while MVR-T3011 IV is designed for intravenous injection and is also global first systemic administered oHSV in clinical stage. MVR-T3011, ImmVira’s proprietary 3-in-1 oHSV, is a novel genetic engineered oHSV which aims to achieve the most favorable profile of attenuated HSV-1 with replication potency in tumor cells and highly restricted replication in normal cells. In addition, MVR-T3011 carries two latest and well-validated exogenous genes, PD-1 antibody and IL-12, to further enhance immune responses of tumor microenvironment.

OnQuality Announces FDA Clearance of IND Application for OQL051, for the Prophylaxis of Chemotherapy-Induced Diarrhea

On June 6, 2023 OnQuality Pharmaceuticals ("OnQuality"), a targeted oncology supportive therapy company developing innovative medications to address unmet needs in oncodermatology and oncogastroenterology (cancer therapy-induced toxicities occurring in the skin and gastrointestinal tract) and to improve the quality of life for patients receiving anticancer medications, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for its drug candidate, OQL051, for the prophylaxis of chemotherapy-induced diarrhea (CID) (Press release, OnQuality Pharmaceuticals, JUN 6, 2023, View Source [SID1234632530]).

CID is a common and often debilitating toxicity affecting up to 90% of patients receiving chemotherapy. CID can cause dehydration, electrolyte imbalance, malnutrition, and infection, which may lead to hospitalization, cardiovascular compromise, and in some cases death. Prevention of moderate to severe CID often requires dose reduction. Treatment of CID may require interruption or even permanent discontinuation of chemotherapy, and potentially compromising the effectiveness of cancer therapy.

OQL051 – a first-in-disease, oral, gut-restricted CDK4/6 inhibitor – is designed to prevent the development of CID in patients receiving cytotoxic chemotherapies. The drug works by temporarily arresting the rapidly dividing intestinal mucosal cells in G1 phase. OQL051 locally targets cells of the digestive tract, transiently preventing cell division. This protects the intestinal lining from chemotherapy damage. Preclinical studies have demonstrated that OQL051, when given prior to chemotherapy, delays the onset and reduces the severity of CID without compromising the anti-tumor activity of chemotherapy agents.

"We are delighted to receive IND clearance for OQL051. This is a significant milestone for OnQuality and for patients suffering from CID," said Hong Tang, MD, FACP, Chief Medical Officer at OnQuality. "Prevention of CID is a major unmet medical need. We believe that OQL051 has the potential to make a meaningful difference in the lives of patients who suffer from cancer and the toxic effects of cancer treatment."

"Along with the OQL036 (for the prophylaxis of capecitabine-induced hand-food syndrome in onco-dermatology) clinical clearance by FDA in April this year, the newly cleared OQL051 allows us to advance our drug development in onco-gastroenterology, the second pillar of OnQuality pipeline," added by Jacob Song, Global Regulatory Lead and Director.

OnQuality plans to initiate a Phase I/II clinical trial in coming months to evaluate the safety in healthy volunteers, as well as safety and preliminary efficacy of the drug in cancer patients who plan to receive fluorouracil (5-FU) and irinotecan-based chemotherapy.

About Chemotherapy-Induced Diarrhea and OQL051

Chemotherapy-induced diarrhea (CID) is a common toxicity of chemotherapy, which plays a crucial role in the treatment of cancer. CID can range in severity from mild to severe, and can cause symptoms such as frequent bowel movements, abdominal pain, which may lead to dehydration, electrolyte imbalance, infection, and other potentially serious complications. There are currently no FDA-approved therapies for prevention of CID. The effectiveness of current symptom relief strategies is limited.

OQL051, a first-in-disease, oral, gut-restricted CDK4/6 inhibitor, is designed to prevent the development of CID in patients receiving cytotoxic chemotherapies. The drug works by temporarily arresting the rapidly dividing intestinal mucosa cells in the G1 phase throughout chemotherapy administration. This protects the intestinal lining from chemotherapy damage. Preclinical studies demonstrated that OQL051, when given prior to chemotherapy, delayed the onset and reduced the severity of CID in animal models. Due to its low systemic exposure, the anti-tumor activity of chemotherapeutic agents was not affected.

Investor presentation

On June 6, 2023 Oncocyte presented its investor presentation (Presentation, Oncocyte, JUN 6, 2023, View Source [SID1234632529]).

Zai Lab and Novocure Announce LUNAR Phase 3 Clinical Trial Demonstrates Statistically Significant and Clinically Meaningful Extension in Overall Survival for Patients with Metastatic Non-Small Cell Lung Cancer After Platinum-Based Therapies

On June 6, 2023 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) and Novocure (NASDAQ: NVCR) reported positive results from the phase 3 LUNAR clinical trial evaluating the use of Tumor Treating Fields (TTFields) therapy together with standard therapies for the treatment of non-small cell lung cancer (NSCLC) at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Zai Laboratory, JUN 6, 2023, View Source [SID1234632527]). The LUNAR trial met its primary endpoint with a statistically significant and clinically meaningful 3-month improvement in median overall survival (OS) when TTFields therapy was added to standard therapies (HR: 0.74, P=0.035).

Patients randomized to receive TTFields therapy together with standard therapies (n=137) demonstrated median OS of 13.2 months compared to 9.9 months in patients treated with standard therapies alone (n=139). A profound OS benefit from TTFields therapy was demonstrated in the immune checkpoint inhibitor (ICI) subgroup. Patients randomized to receive TTFields therapy and physician’s choice ICI (n=66) demonstrated a median OS of 18.5 months versus a median OS of 10.8 months in patients treated with ICIs alone (n=68; HR=0.63; P=0.03). Patients randomized to receive TTFields therapy and docetaxel (n=71) had a positive survival trend with a median OS of 11.1 months vs 8.7 months in patients treated with docetaxel alone (n=71). TTFields therapy was well-tolerated with no added systemic toxicities and few grade 3 (no grade 4 or 5) device-related adverse events.

"The results of the LUNAR study are highly encouraging," said primary investigator Ticiana Leal, M.D., a researcher and medical oncologist at Winship Cancer Institute of Emory University and associate professor and director of the Thoracic Medical Oncology Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta. "The LUNAR trial is the first study in more than seven years to show a significant improvement in overall survival in metastatic non-small cell lung cancer post-platinum chemotherapy. I am heartened by this progress and the potential of this innovative therapy to help many metastatic lung cancer patients in need of new treatment choices following platinum therapy, without added systemic toxicity."

"The significant improvement in overall survival as demonstrated in the LUNAR study is groundbreaking. Lung cancer is the leading cause of cancer-related death in China, and non-small cell lung cancer is the most common form of this disease. The prognosis is often very poor for patients who progress after treatment with a platinum-containing regimen in the front-line setting," said professor Li Zhang, M.D., Sun Yat-sen University Cancer Center. "I am very excited that this novel, non-invasive device can bring significant benefit to patients living with metastatic NSCLC in China."

Baseline characteristics were well balanced between cohorts: median age was 64 years (range, 22-86); 65% male; 96% of patients had an ECOG performance status of 0-1. Patients were enrolled at sites in North America (30%), Western Europe (30%), Eastern Europe (30%) and East Asia (9%). One-year survival rates for patients treated with TTFields therapy together with standard therapies was 53% versus 42% for patients treated with standard therapies alone (P=0.04). A landmark three-year survival analysis for patients treated with TTFields therapy together with standard therapies demonstrated a nearly threefold improvement, extending to 18% versus 7% for patients treated with standard therapies alone (P=0.015). Median progression-free survival (PFS) for patients treated with TTFields therapy together with standard therapies was 4.8 months versus 4.1 months in patients treated with standard therapies alone.
Of patients randomized, 89% had one prior line of systemic therapy and 31% of patients randomized had been treated with an ICI (58% of patients randomized to the docetaxel cohort and 2% of patients randomized to the ICI cohort). ICIs were approved for first-line NSCLC in 2017 during the conduct of the LUNAR study, and PD-L1 expression data were collected thereafter in geographic regions where ICIs had been adopted. Tumor Proportion Scores were available for 151 patients globally (55%) and were well balanced across the cohorts. In all patients treated with ICI and with measured Tumor Proportion Scores, 63% had PD-L1 expression >1%, which is in-line with real-world data. PD-L1 expression data were collected from 83% of patients (69 of 83 patients) enrolled at U.S. sites and were well balanced across the four cohorts.
1

PD-L1 Status:
PD-L1 Expression TTFields + SOC (n=137) SOC
(n=139) TTFields + ICI (n=66) ICI
(n=68) TTFields + DTX (n=71) DTX
(n=71)
<1% 17% 17% 18% 24% 16% 10%
1-49% 27% 29% 26% 27% 28% 31%
>50% 7% 13% 8% 12% 7% 14%

DTX = docetaxel; ICI = immune checkpoint inhibitor; SOC = standard of care
Novocure has submitted the LUNAR clinical trial results for publication in a leading, peer-reviewed medical journal. The LUNAR clinical trial data are expected to serve as the basis for a Premarket Approval (PMA) submission to the U.S. Food and Drug Administration in the second half of 2023. Zai Lab contributed to the China portion of the LUNAR study and plans to submit a Marketing Authorization Application (MAA) to China’s National Medical Products Administration (NMPA) following Novocure’s submission to the FDA.

"I would like to thank our patients, their families and caregivers for participating in the LUNAR trial," said William Doyle, Novocure’s Executive Chairman. "I would also like to thank Dr. Leal and all of our investigators for their expertise and dedication to advancing the care of patients. The LUNAR trial results represent tremendous progress for the treatment of metastatic non-small cell lung cancer, and the LUNAR trial demonstrates the broad and versatile potential of TTFields therapy in improving the survival of cancer patients with high unmet needs. We are energized by the LUNAR results and are moving forward quickly to make TTFields therapy available to patients with metastatic non-small cell lung cancer."

"Each year in China, approximately 740,000 patients are newly diagnosed with non-small cell lung cancer, and most patients are diagnosed at an advanced stage. The LUNAR trial results demonstrate the potential of TTFields to meaningfully extend survival for many patients with advanced, platinum-resistant NSCLC," said Dr. Samantha Du, Founder, Chairperson, and Chief Executive Officer of Zai Lab. "We are pleased to have been able to contribute to the LUNAR study, and we look forward to working with Novocure to bring TTFields to patients with metastatic NSCLC as soon as possible."

Novocure is dedicated to advancing TTFields therapy for patients with solid tumors. The LUNAR clinical trial is the first of four phase 3 clinical trials expected to readout by the end of 2024 studying the use of TTFields therapy for the treatment of solid tumors of the brain, torso and abdomen. Based on the strength of the LUNAR data, Novocure intends to launch additional phase 3 trials evaluating TTFields therapy in earlier lines of treatment and together with ICIs and other standards of care.

In addition to LUNAR, Zai Lab participated in two of Novocure’s ongoing phase 3 clinical trials – the METIS trial (brain metastases resulting from NSCLC) and the PANOVA-3 trial (pancreatic cancer). Zai Lab also conducted the EF-31 phase 2 trial, in collaboration with Novocure, studying the use of TTFields in the treatment of gastric cancer in China.

Investor Event details

Novocure will host an investor event at 2 p.m. CDT on Tuesday, June 6, 2023. The event will include a presentation and discussion of the LUNAR clinical trial data, featuring leading thoracic oncologists, investigators, and Novocure leadership. A live webcast of the event will be available on the investor relations page of www.novocure.com. For more information or to request in-person attendance, please contact Novocure investor relations ([email protected]).

About LUNAR

LUNAR is a phase 3 trial testing the safety and effectiveness of TTFields therapy when used together with ICI or docetaxel (experimental arm) versus ICI or docetaxel alone (control arm) for patients with metastatic NSCLC who progressed during or after platinum-based therapy. The primary endpoint is superior overall survival of patients treated with TTFields therapy plus ICI or docetaxel versus ICI or docetaxel alone. The powered secondary endpoints are superior overall survival of patients treated with TTFields therapy plus ICI versus ICI cohort and superior overall survival of patients treated with TTFields therapy plus docetaxel versus docetaxel alone. TTFields therapy is intended principally for use with other concomitant standard of care treatments, and LUNAR was designed to generate data that contemplates multiple outcomes, all of which Novocure believes will be clinically meaningful.

About NSCLC in China

Lung cancer is the most commonly diagnosed cancer type and the leading cause of cancer death in China. There were approximately 871,000 new cases and 767,000 deaths of lung cancer in China in 2022, respectively.1 NSCLC accounts for approximately 85% of lung cancer, and approximately 70% of NSCLC is locally advanced or metastatic at initial diagnosis. Similar to the global clinical practice, physicians use different combinations of surgery, radiation and pharmacological therapies to treat NSCLC, depending on the stage of the disease. Surgery, which may be curative in a subset of patients, is usually used in early stages of the disease. Since 1991, radiation with a combination of platinum-based chemotherapy drugs has been the first-line standard of care for locally advanced or metastatic NSCLC. Certain immune checkpoint inhibitors have been approved for the first-line treatment of NSCLC and the standard of care in this setting appears to be evolving rapidly. The standard of care for second-line treatment is also evolving and may include platinum-based chemotherapy for patients who received immune checkpoint inhibitors as their first-line regimen, pemetrexed, docetaxel or immune checkpoint inhibitors.

Corporate presentation

On June 6, 2023 Xenetic Biosciences presented its corporate presentation (Presentation, Xenetic Biosciences, JUN 6, 2023, View Source [SID1234632526]).