On June 5, 2024 Pierre Fabre Laboratories reported the filing of an investigational new drug ("IND") application to the U.S. Food and Drug Administration ("FDA") to initiate a first-in-human (FIH) Phase I/II clinical trial with PFL-002/VERT-002 for solid tumors including non-small cell lung cancer (NSCLC) (Press release, Pierre Fabre, JUN 5, 2024, View Source [SID1234644149]).

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The PFL-002/VERT-002 Phase I/II trial is a multi-center, international study aimed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of PFL-002/VERT-002 in NSCLC patients with MET alterations, including those acquired as resistance mechanism to other treatments. The FDA will review the application and determine its acceptability.

"We are looking forward to initiating the first-in-human trial of PFL-002/VERT-002 later this year. We are confident that this new drug holds significant promise, as a novel therapeutic option with a differentiated mechanism of action, for patients facing MET-altered solid tumors, including NSCLC" said Francesco Hofmann, Head of Research and Development for Medical Care at Pierre Fabre Laboratories.

About PFL-002/VERT-002

PFL-002/VERT-002 is a monoclonal antibody developed by Vertical Bio, offering a unique and differentiating mechanism of action, acting as a degrader of c-MET, a known disease driver in patients with solid tumors, including non-small cell lung cancer (NSCLC) presenting mutations or amplification of MET. The antibody has been optimized preclinically by Vertical Bio, which has been acquired by Pierre Fabre Laboratories.

Pierre Fabre Laboratories is progressing PFL-002/VERT-002 into clinical development and hope to enroll a first patient in the FIH trial by end 2024.

On June 5, 2024 Oricell Therapeutics, a pioneering clinical-stage biopharmaceutical company, reported the two-year long-term follow-up results of OriCAR-017, an open-label Phase I study evaluating GPRC5D-targeted CAR-T therapy in patients with relapsed/refractory multiple myeloma (RRMM), in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, OriCell Therapeutics, JUN 5, 2024, View Source [SID1234644148]).

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Efficacy & Durability of OriCAR-017 in RRMM Patients
The updated data demonstrates that OriCAR-017 elicits deep and durable responses in RRMM patients as well as a favorable safety profile, including those refractory to anti-CD38 therapies, PIs, IMIDs, and those who have failed BCMA targeting CAR-T treatment. The long-term efficacy and safety follow-up results support OriCAR-017 as a promising therapeutic approach for RRMM. Currently, Oricell is smoothly advancing the clinical development of OriCAR-017 in both China (NCT06182696) and the United States (NCT06271252).

As of January 16, 2024, all ten patients responded well to OriCAR-017, with the last patient having completed a 24-month follow-up. The overall response rate (ORR) was 100.0%, with a stringent complete response rate (sCR) of 80.0% and a very good partial response rate (VGPR) of 20.0%. All patients achieved 100% minimal residual disease negativity (MRD) at day 28, which was further confirmed as 100% negative at the 3-months follow-up. The median duration of response (mDoR) was 10.43 months (95% CI, 5.00-17.00), the median progression-free survival (mPFS) was 11.37 months (95% CI, 5.93-18.00), and the median overall survival (mOS) had not yet been reached (7 patients were still under survival follow-up, 1 patient died due to disease progression, and 2 patients died from COVID-19). In the high-dose group, where 67% of patients were previously treated with BCMA CAR-T, the mDoR was 17.23 months (95% CI, 7.33-NR), and the mPFS was 19.10 months (95% CI, 8.30-NR). Currently, a BCMA CAR-T-treated patient is still in remission (>24 months).

Safety Profile of OriCAR-017 in the Treatment of RRMM
The therapy was well-tolerated, with 9 out of 10 patients (90%) experiencing Grade 1 cytokine release syndrome (CRS) and only 1 patient (10%) experiencing Grade 2 CRS. No Grade 3 or higher CRS was observed. The median time to CRS onset was 2 days (range 1-9 days), with a median duration of 6 days (range 3-9 days). No immune effector cell-associated neurotoxicity syndrome (ICANS) or dose-limiting toxicities (DLTs) were observed. There were no serious adverse events (SAEs) or treatment-related deaths, cerebellar disorders, or delayed infections reported.

Pharmacokinetics (PK) of OriCAR-017 in RRMM Patients
There were no pharmacokinetic differences between dose levels, with a Cmax of 7354.7 copies/μL and an AUC0-28 of 68587 copies•day/μg. At high doses, CAR-T cells were still detectable at 9 months, and after 21 months of follow-up, one patient had CAR-T cell expansion above the lower limit of quantitation (LLOQ). Patients with Tlast ≥ 9 months had a longer PFS compared to those with Tlast < 9 months.

G5 Expression in Response to OriCAR-017 Treatment in RRMM
No correlation was observed between antigen expression and therapeutic efficacy. Baseline data from all patients showed positive GPRC5D expression in bone marrow CD138+ plasma cells (MMPC), while 50% of relapsed patients showed downregulated expression detected by flow cytometry.

OriCAR-017 Demonstrates Significant Potential in Severely Progressed RRMM Patients
It’s worth noting that the study included patients with complex and advanced disease characteristics. Among the ten R/R MM patients, 40% had extramedullary disease (EMD), 50% had undergone one or more BCMA-directed CAR-T treatments, 70% had high-risk cytogenetics, 70% were classified as ECOG 2 score status, and 80% were at International Staging System (ISS) stages II & III. OriCAR-017 demonstrates its potential as a safe and efficacious treatment option for RRMM patients, marking a substantial progress in the fight against multiple myeloma and offering hope to those facing demanding health conditions.

Details for the presentation as below:
Oral Presentation #7511
Title: OriCAR-017, a novel GPRC5D-targeting CAR-T, in patients with relapsed/refractory multiple myeloma: Long term follow-up results of phase 1 study (POLARIS).
Session Type:Rapid Oral Abstract Session
Session Title: Hematologic Malignancies—Plasma Cell Dyscrasia
Link: View Source

About OriCAR-017

OriCAR-017, a chimeric antigen receptor (CAR) T cell therapy targeting GPRC5D, is a groundbreaking innovation in the treatment of relapsed/refractory multiple myeloma (RRMM). Leveraging Oricell Therapeutics’ cutting-edge proprietary technology platforms, OriCAR-017 exhibits clearly differentiated binding avidity, persistence, anti-tumor efficacy and safety profile. OriCAR-017 received IND approval from FDA in Jan 2024 after its approval by NMPA in 2023. Impressive clinical results from the POLARIS study continue to be released.

Currently, Oricell has assembled a skilled team to operate in both the U.S. and China, collaboratively accelerating pipeline development globally.

On June 5, 2024 AbbVie (NYSE: ABBV) reported that the first patient has been treated with investigational ABBV-383 in the CERVINO Phase 3 study (Press release, AbbVie, JUN 5, 2024, View Source [SID1234644147]). ABBV-383 is a distinctive B-cell maturation antigen (BCMA) and CD3 bispecific antibody T-cell engager composed of bivalent BCMA-binding domains allowing for high BCMA-avidity and a low-affinity CD3 binding domain.1 ABBV-383 is being evaluated in a Phase 3, multicenter, randomized, open-label study compared with standard available therapies in patients with r/r MM who received at least two lines of prior therapy.

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"Despite notable advances in treatment, most patients with multiple myeloma will eventually relapse. Patients with advanced disease, especially in the community setting, often have limited access to novel treatment options and existing options have a high treatment burden, including frequent dosing," said Dr. Peter Voorhees, clinical professor of medicine, director of plasma cell disorders, Atrium Health Levine Cancer Institute. "The CERVINO Phase 3 trial is designed to evaluate the efficacy of ABBV-383 with monthly dosing and we look forward to seeing the data as it emerges."

Multiple myeloma is a blood cancer characterized by abnormal proliferation of plasma cells, which can cause end-organ damage and is the second most commonly occurring blood cancer in the world.2 An estimated 176,000 people globally were diagnosed with multiple myeloma in 2020, and 117,000 people died from the disease.3

"The start of the CERVINO Phase 3 trial marks an important step forward in AbbVie’s continued commitment to advance new oncology treatments and elevate the standard of care for blood cancer patients," said Mariana Cota Stirner, M.D., vice president, therapeutic area head oncology, hematology, AbbVie. "ABBV-383 is being evaluated with monthly dosing from the beginning of treatment, with the goal of maximizing treatment simplicity for physicians and patients, if proven in the clinical trials."

About the CERVINO Study

CERVINO (NCT06158841) is a global, Phase 3, multicenter, randomized, open-label, parallel-group study evaluating ABBV-383 in adult patients (≥18 years) with r/r MM and an Eastern Cooperative Oncology Group performance status ≤2 who received at least two prior lines of therapy, including exposure to a PI, an IMiD, and an anti-CD38 mAb. Patients who received prior BCMA-targeted therapy will be excluded. Patients will be randomized 1:1 to receive intravenous ABBV-383 60mg Q4W or the investigator’s choice of SAT (carfilzomib + dexamethasone, elotuzumab + pomalidomide + dexamethasone, or selinexor + bortezomib + dexamethasone), and will continue treatment until confirmed progressive disease or other discontinuation criteria are met.

The dual primary end points are progression-free survival and overall response rate. Secondary end points include overall survival, complete response (CR) or better, very good partial response or better, rate of minimum residual disease negativity, and change in disease symptoms and physical functioning.

Approximately 140 sites globally will enroll approximately 380 total patients.

Additional information about the study can be found at View Source under the identifier NCT06158841.

About ABBV-383

ABBV-383 is an investigational distinctive BCMA x CD3 bispecific antibody T-cell engager composed of bivalent high-avidity BCMA-binding domains, a low-affinity CD3-binding domain designed to reduce cytokine release, and a silenced Fc tail designed for an extended half-life that may support once every 4-week (Q4W) dosing. Clinical relevance of these structure activity relationships has not been established.

BCMA is highly expressed on the surface of malignant plasma cells in multiple myeloma, making it an ideal target for therapy. BCMA plays a crucial role in the survival of myeloma cells by promoting their growth and inhibiting their apoptosis (programmed cell death).

On June 5, 2024 RemeGen Co., Ltd. ("RemeGen" or "the Company") (9995.HK, SHA: 688331), a commercial-stage biotechnology company, reported its innovation in the field of global cancer treatment at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO 2024) held in Chicago from May 31-June 4, 2024, sharing major research results including its proprietary antibody drug conjugates (ADCs) Disitamab Vedotin (RC48) and RC88 (Press release, RemeGen, JUN 5, 2024, View Source [SID1234644146]). RemeGen’s innovative drugs featured in one Clinical Science Symposium, five Poster presentations, and ten online Abstracts at ASCO (Free ASCO Whitepaper) 2024, covering multiple cancer types including gastric and bladder cancer, and gynecological tumors in studies that included both monotherapy and combination therapies.

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Dr. Jianmin Fang, CEO of RemeGen, commented, "It is always such an honor to present our latest research findings on an internationally renowned stage such as ASCO (Free ASCO Whitepaper) Annual Meeting 2024. This not only demonstrates RemeGen’s leading position in the field of antibody-drug conjugates in China but also proves our commitment to continuing our research efforts to provide effective treatment options for patients worldwide."

Clinical Science Symposium

First author Professor Song Li from Qilu Hospital of Shandong University gave an oral presentation at a Clinical Science Symposium at ASCO (Free ASCO Whitepaper) 2024 based on a randomized, controlled (RCT) multicenter, single-arm, Phase II trial investigating the efficacy of RemeGen’s disitamab vedotin (RC48) combined with toripalimab and the oral fluoropyrimidine S-1 in first-line HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma.

Poster Sessions

First author Professor Sheng Xinan from Peking University Cancer Hospital presented RemeGen’s poster session (Poster #263) of a Phase II study of neoadjuvant treatment with disitamab vedotin plus toripalimab in patients with HER2-expressing muscle-invasive bladder cancer (MIBC) focusing on the preliminary efficacy and safety results of RC48-C017. The standard of care for MIBC is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy plus pelvic lymph node dissection (RC + PLND). Disitamab vedotin monotherapy, or combined therapy with toripalimab, showed promising anti-tumor activity in metastatic urothelial carcinoma. This Phase II trial aimed to evaluate the safety and efficacy of disitamab vedotin plus toripalimab as perioperative therapy in MIBC patients and the interim results presented at ASCO (Free ASCO Whitepaper) showed promising efficacy results with a manageable safety profile in operable MIBC patients. These results support further investigation for disitamab vedotin plus toripalimab in this population.

Other poster presentations included a Phase II multi-center study in poster session (poster #311a) on adjuvant or rescue disitamab vedotin (RC48-ADC) for high-risk non-muscle invasive bladder cancer with HER2 expression; and a prospective, single-arm, single-center clinical study in poster session (poster #513a) on disitamab vedotin combined with toripalimab in patients with advanced penile cancer who have progressed on treatment or are intolerant to cisplatin chemotherapy.

Online Abstract Publications

Ten other online abstracts accepted by ASCO (Free ASCO Whitepaper) reflected results of RemeGen’s RC48 and RC88 in bladder, breast, and GI cancers, demonstrating the Company’s prolific innovation in global cancer treatment.

About ASCO (Free ASCO Whitepaper)

The ASCO (Free ASCO Whitepaper) 2024 meeting is the premier event for strategies to improve quality care in oncology. It provides superb panels featuring experts who are leading and implementing innovative programs focused on value. ASCO (Free ASCO Whitepaper)’s diverse network of nearly 42,350 oncology professionals recognizes ASCO (Free ASCO Whitepaper)’s dedication to providing the highest-quality resources in education, policy, the pioneering of clinical research, and above all, advancing the care for patients with cancer.

On June 5, 2024 MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the Standard Market of the Tokyo Stock Exchange (Code Number: 4875), reported that it has received a Notice of Allowance from the U.S. Patent and Trademark Office for a pending patent application which covers MN-166 (ibudilast) for the prevention of metastasis in various cancers including pancreatic cancer, lung cancer, breast cancer, colorectal cancer, melanoma, and ovarian cancer (Press release, MediciNova, JUN 5, 2024, https://investors.medicinova.com/news-releases/news-release-details/medicinova-receives-notice-allowance-new-patent-covering-mn-31 [SID1234644145]).

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Once issued, this patent is expected to expire no earlier than July 2042. The allowed claims cover the use of MN-166 (ibudilast) in combination with one or more additional therapies including chemotherapy, immunotherapy, radiotherapy, photodynamic therapy, epigenetic therapy, and liver-directed therapy and others. The allowed claims specifically cover the use of MN-166 (ibudilast) for preventing, ameliorating, or minimizing metastasis of various cancers including pancreatic cancer, lung cancer, breast cancer, colorectal cancer, melanoma, or ovarian cancer. The allowed claims cover oral administration, a wide range of doses, a range of different dosing frequencies, and a range of different treatment periods.

Kazuko Matsuda, MD, PhD, MPH, Chief Medical Officer of MediciNova, Inc., commented, "Cancer metastasis is often the major driver of cancer-related deaths rather than the primary cancer. Recently we were granted a patent *1 to cover preventing metastasis of uveal melanoma. We are delighted to see our growing intellectual property patent portfolio and value of MN-166 (ibudilast) increase with the addition of patents covering the prevention of metastasis of various solid tumors."

*1: MediciNova Receives Notice of Allowance for New Patent Covering MN-166 (ibudilast) for the Prevention of Metastasis of Eye Cancer
https://investors.medicinova.com/news-releases/news-release-details/medicinova-receives-notice-allowance-new-patent-covering-mn-30

About MN-166 (ibudilast)

MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It is in late-stage clinical development for the treatment of neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); and is also in development for glioblastoma, Long COVID, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) was evaluated in patients that are at risk for developing acute respiratory distress syndrome (ARDS).