On June 1, 2024 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, reported Phase 1 clinical data of IBI343 (TOPOi anti-CLDN18.2 ADC) for the treatment of advanced pancreatic ductal adenocarcinoma or biliary tract cancer at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (NCT05458219) (Press release, Innovent Biologics, JUN 1, 2024, View Source [SID1234643951]). In addition, clinical data of the treatment for advanced gastric or gastroesophageal tumors from this Phase 1 trial will be published in oral presentation at the ESMO (Free ESMO Whitepaper) Gastrointestinal Cancers Congress 2024 this month.

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Dr. Hui Zhou, Senior Vice President of Innovent Biologics, said, "We are excited to share the latest clinical development updates on IBI343 at ASCO (Free ASCO Whitepaper). As an innovative TOPOi ADC, IBI343 showed a positive clinical signal in subjects with advanced pancreatic cancer and the incidence of grade 3 or above gastrointestinal adverse events is low. It is the first CLDN18.2 ADC to achieve a breakthrough in this difficult-to-treat cancer and shed light on the exploring directions to this therapeutic field. We will continue to follow up on the clinical data update of IBI343. As one of the few biopharmaceutical companies with leading R&D capabilities in both immunotherapy (IO) and antibody-drug conjugates (ADCs), we will also explore combination therapy of IBI343 and its therapeutic potential in other solid tumors such as gastric cancer for the benefit of more patients."

Safety and efficacy of IBI343 (anti-CLDN18.2 ADC) in patients with advanced pancreatic ductal adenocarcinoma or biliary tract cancer: preliminary results from a Phase I study

Abstract#:3037

This Phase I study is conducted in China and Australia, aiming to evaluate the safety, tolerability and preliminary efficacy of IBI343 in subjects with advanced solid tumors. Data on patients with advanced pancreatic ductal adenocarcinoma or biliary tract cancer were presented at this congress. As of December 19, 2023, a total of 35 patients with advanced pancreatic ductal adenocarcinoma (PDAC) or biliary tract cancer (BTC) were enrolled, and all subjects had received at least one prior systemic treatment, with a median of 2 lines of treatment.

The results showed that:

As of January 15, 2024, 25 subjects had performed at least one post-baseline tumor evaluation. 7 subjects achieved partial response (PR), 5 of which were PDAC patients, 2 were BTC patients. The objective response rate (ORR) was 28.0% (95% CI: 12.1-49.4), and the disease control rate (DCR) was 80.0% (95% CI: 59.3-93.2).
In the 6 mg/kg dose group, 13 subjects with CLDN18.2 1/2/3+≥60% had at least one post-baseline tumor assessment, of which 5 achieved PR with an ORR of 38.5% (95%CI: 13.9-68.4) and a DCR of 84.6% (95% CI：54.6-98.1). Among the 10 subjects with advanced PDAC in this subgroup, the ORR was 40% (95% CI: 12.2-73.8). DoR and PFS data are not mature yet.
In terms of safety, 80.0% of subjects experienced treatment-related adverse events (TRAEs). Common TRAEs were anemia (42.9%), neutrophil count decreased (28.6%), nausea (25.7%), vomiting (25.7%) and white blood cell count decreased (22.9%). 25.7% of participants developed ≥ grade 3 TRAEs. No TRAE led to death.
Professor Xianjun Yu, Fudan University Shanghai Cancer Center, said: "Advanced pancreatic cancer and biliary tract cancer progress rapidly while the clinical course is initially insidious. Most patients are often not diagnosed until advanced stages with poor prognosis. Currently, chemotherapy remains a mainstay of the first-and-second line treatments for advanced pancreatic cancer and bile duct cancer. The clinical options for second-line treatment are particularly limited and cannot bring significant clinical benefits to patients. FOLFOX is used as a second-line standard of care for advanced biliary tract cancer with an ORR of 5%, a median overall survival OS of 6.2 months [1]. In the second-line treatment of pancreatic cancer, the response rate to chemotherapy is only 6%~16%, and the median survival time is only about 3~6 months [2].

CLDN18.2 has become a promising target for the treatment of patients with digestive malignancies, which has a high expression rate in pancreatic cancer and biliary tract cancer. The expression rate in pancreatic cancer patients is 50%~70% [3], and 52% of biliary tract cancer [4]. Promising clinical benefit of the novel TOPOi anti-CLDN18.2 ADC IBI343 has been observed in subjects with advanced pancreatic cancer and biliary tract cancer. Particularly in advanced pancreatic cancer participants with high CLDN18.2 expression, it showed encouraging efficacy signals and a tolerable safety profile, which may bring patients novel and effective treatment options."

About IBI343（Anti CLDN18.2 ADC）

IBI343 is a recombinant human anti-Claudin 18.2 monoclonal antibody-drug conjugate (ADC) developed by Innovent Biologics. IBI343 binds to the Claudin 18.2-expressing tumor cells, the Claudin 18.2 dependent ADC internalization will occur and the drug is released resulting in DNA damage and eventually apoptosis of the tumor cells. The freed drug can also diffuse across the plasma membrane to reach and kill the neighboring cells, resulting in "bystander killing effect".

As an innovative TOPOi ADC, IBI343 has demonstrated tolerable safety and encouraging efficacy signals in this phase I clinical studies. The therapeutic potential of IBI343 is currently being explored in tumor types such as gastric cancer and pancreatic cancer. In May 2024, The National Medical Products Administration (NMPA) of China granted breakthrough therapy designation (BTD) to IBI343 for use as a single agent in patients with claudin 18.2–positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who experienced disease progression following 2 prior lines of systemic treatment. The multi-center Phase 3 trial of IBI343 for this indication is in preparation.

On June 1, 2024 CStone Pharmaceuticals (HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending approval of sugemalimab in combination with chemotherapy as a first-line treatment for metastatic non-small cell lung cancer (NSCLC), which is one of the largest cancer indications and a leading cause of cancer death in the world (Press release, CStone Pharmaceauticals, JUN 1, 2024, View Source [SID1234643950]). Sugemalimab is expected to become the first anti-PD-L1 monoclonal antibody (mAb) approved in Europe for both first-line squamous and non-squamous NSCLC, regardless of PD-L1 expression, also making CStone the very first biopharmaceutical company in China to potentially launch a domestic anti-PD-L1 mAb in ex-China markets.

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Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, said, "The positive opinion from EMA CHMP normally indicates an upcoming approval for market authorization by the European Commission, marking a significant milestone not only for sugemalimab but also for CStone and the entire pharmaceutical industry in China. The CHMP recommendation brings us closer to delivering this innovative treatment to European patients with lung cancer, and it also highlights a major milestone in CStone’s global strategy. Stage IV NSCLC is the first of several other indications where sugemalimab has been shown to bring significant benefits and we are planning to file for registration in these other important indications including stage III NSCLC, gastric cancer, esophageal cancer, etc. In addition, we have been actively engaging in substantive discussions with numerous other potential partners in various countries or regions to follow our recently announced strategic commercial collaboration with Ewopharma in Central Eastern Europe and Switzerland. We are confident and eagerly anticipate collaborating to swiftly propel sugemalimab into broader global markets and benefiting more patients across multiple indications. I would also like to thank the CStone team for their hard work and persistence over the years to achieve this important milestone."

CHMP recommendation is primarily based on the results of GEMSTONE-302, a multi-center, randomized, double-blind, Phase 3 clinical trial. Sugemalimab in combination with chemotherapy significantly improved PFS and OS compared to placebo in combination with chemotherapy in previously untreated stage IV NSCLC patients. The study results have been published in The Lancet Oncology and Nature Cancer and reported in oral sessions at various international academic conferences.

Sugemalimab is an anti-PD-L1 monoclonal antibody developed by CStone, which has been approved in China for five indications, including stage III and IV NSCLC, extranodal NK/T-cell lymphoma, esophageal squamous cell carcinoma, and gastric cancer. Additionally, the U.K. Medicines and Healthcare products Regulatory Agency (MHRA) is currently reviewing the marketing authorization application for sugemalimab combined with chemotherapy as a first-line treatment for metastatic NSCLC. The company is also in communications with regulatory authorities such as the EMA, MHRA, and U.S. Food and Drug Administration (FDA) regarding additional indications for sugemalimab and is actively seeking development and commercialization partnerships in other countries and regions worldwide.

About Lung Cancer
In 2020, lung cancer was the third most diagnosed cancer in Europe and the leading cause of cancer-related mortality, accounting for one fifth of cancer deaths.i Approximately fifty to seventy percent of lung cancer cases in Europe are diagnosed in Stage IVii Globally, it is estimated that NSCLC accounts for approximately 85% of all lung cancers.iii

About Sugemalimab
The anti-PD-L1 monoclonal antibody sugemalimab was developed by CStone using OmniRat transgenic animal platform, which allows creation of fully human antibodies in one step. Sugemalimab is a fully human, full-length anti-PD-L1 immunoglobulin G4 (IgG4) monoclonal antibody, which may reduce the risk of immunogenicity and toxicity for patients, a unique advantage over similar drugs. Sugemalimab’s unique molecular design enables a dual mechanism of action that not only blocks PD-1/PD-L1 interaction, but also induces antibody dependent cellular phagocytosis (ADCP) by cross-linking PD-L1 expressing tumor cells with tumor associated macrophages (TAMs) without harming Effector T-cells. This differentiation has resulted in potentially best-in-class efficacy/safety across a variety of tumor types.

The National Medical Products Administration (NMPA) of China has approved sugemalimab for five indications:

In combination with chemotherapy as first-line treatment of patients with metastatic squamous and non-squamous NSCLC;
For the treatment of patients with unresectable Stage III NSCLC whose disease has not progressed following concurrent or sequential platinum-based chemoradiotherapy;
For the treatment of patients with relapsed or refractory extranodal NK/T-cell lymphoma;
In combination with fluorouracil and platinum-based chemotherapy as first-line treatment of patients with unresectable locally advanced, recurrent or metastatic ESCC; and
In combination with fluoropyrimidine- and platinum-containing chemotherapy as first-line treatment for unresectable locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma with a PD-L1 expression (Combined Positive Score [CPS] ≥5).
In addition to the EMA, the UK MHRA has also accepted the MAA for sugemalimab in combination with chemotherapy as first-line treatment for metastatic NSCLC. The application is currently under review.

On June 1, 2024 Jacobio Pharma (1167.HK), a clinical-stage oncology company focusing on undruggable targets, reported updated data of a KRAS G12C inhibitor glecirasib (JAB-21822) in combination with a SHP2 inhibitor (JAB-3312) in frontline non-small cell lung cancer (NSCLC) patients harboring KRAS G12C mutation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting as form of oral presentation (Press release, Jacobio Pharmaceuticals, JUN 1, 2024, View Source [SID1234643949]). Jacobio also presented updated data of pivotal phase II study of glecirasib as form of oral presentation at an education session.

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As of April 7, 2024, 194 patients participated in a phase II trial of using glecirasib combined with JAB-3312 (NCT05288205), of which 102 patients were frontline NSCLC. The median follow-up time was 10.1 months.

In the oral abstract session (Abstract No. 3008), Professor Jun Zhao, chief physician of Beijing Cancer Hospital, the principal investigator of glecirasib combined with JAB-3312 study, presented the clinical data. About 102 frontline NSCLC patients have been enrolled in 7 dose groups. The confirmed objective response rate (cORR) was 64.7% (66/102), the disease control rate (DCR) was 93.1% (95/102), and the median progression-free survival (mPFS) was 12.2 months, respectively.

This trial explored a total of 7 different dose cohorts, and the optimal dose group was glecirasib at 800mg daily combined with JAB-3312 at 2mg daily one week on and one week off. The cORR of the optimal dose group was 77.4% (18/31), and 54.8% (17/31) of patients achieved a deep response with tumors shrinking by more than 50%. The mPFS was not yet mature.

Regarding on the safety data, among the 194 patients, the incidence of grade 3 or 4 treatment-related adverse events (TRAE) was 43.8%, and there was no treatment-related death. Common TRAEs treatment-related adverse events include anemia, hypertriglyceridemia, etc. The safety profile in the frontline NSCLC is similar to that of the overall study population, and the overall safety is manageable.

Professor Jie Wang, chief physician of Beijing Cancer Hospital, commented, "from the above data, it can be seen that the combination therapy of glecirasib and JAB-3312 has a good safety profile, and the efficacy data shows positive therapeutic potential. If the combination of the two oral drugs can show superiority to the existing standard therapy (immunotherapy combined with chemotherapy) in subsequent trials, we anticipate that patients can avoid the side effects of chemotherapy or immunotherapy."

The combination therapy of glecirasib and JAB-3312 is being tested in a Phase III clinical trial of frontline NSCLC with KRAS G12C mutation in China. Andrea Gillam-Wang M.D., Ph.D., Chief Medical Officer and Global Head of R&D of Jacobio, said: "Our R&D efforts have been focusing on patient needs. We look forward to testing this novel combination against standard care chemotherapy and immunotherapy in NSCLC, and potentially replace standard care regimen consisted of multiple intravenous agents with two oral agents."

The new drug application (NDA) of glecirasib monotherapy for the second-line NSCLC with KRAS G12C mutation was granted Priority Review designation by China CDE on May 21, 2024 In the education session of ASCO (Free ASCO Whitepaper), Professor Yuankai Shi, chief physician of Cancer Hospital Chinese Academy of Medical Sciences, updated the data of the Phase II registration trial of NSCLC with KRAS G12C mutation in an oral report.

Jacobio Pharma will hold a data discussion call at 20:00 Beijing time on June 3. Please click the link to register: View Source

About Glecirasib
Glecirasib is a KRAS G12C inhibitor developed by Jacobio. A number of Phase I/II clinical trials of glecirasib are currently ongoing in China, the United States and Europe for patients with advanced solid tumors harboring KRAS G12C mutation. These include combination therapy trials with SHP2 inhibitor JAB-3312 in NSCLC and with cetuximab in colorectal cancer. The pancreatic cancer indication has obtained orphan drug designation in the United States and breakthrough therapy designation in China.

About JAB-3312
JAB-3312 is a highly selective SHP2 allosteric inhibitor with best-in-class potential. Jacobio is currently conducting clinical trials of JAB-3312 in monotherapy and combination therapies with glecirasib and other agents in China, the United States and Europe. The phase III study in combination with KRAS G12C inhibitor Glecirasib has been approved by China CDE in Feb 2024.

On June 1, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that it has released updated data of its novel drug candidate AGP-2449, a FAK/ALK/ROS1 tyrosine kinase inhibitor (TKI), in patients with non-small-cell lung cancer (NSCLC) in a poster presentation at the 60th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, IL (Press release, Ascentage Pharma, JUN 1, 2024, View Source;ascentage-pharma-releases-updated-data-of-fakalkros1-inhibitor-apg-2449-in-patients-with-nsclc-302161192.html [SID1234643948]). This is the third consecutive year in which clinical data from this study of APG-2449 were selected for presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting.

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The ASCO (Free ASCO Whitepaper) Annual Meeting showcases the most cutting-edge research in clinical oncology and state-of-the-art advanced cancer therapies and is the world’s most influential and prominent scientific gathering of the clinical oncology community. Presenting clinical development progress at the ASCO (Free ASCO Whitepaper) Annual Meeting for the seventh consecutive year, Ascentage had four clinical studies of three of the company’s proprietary drug candidates selected for presentations, including an oral report, at ASCO (Free ASCO Whitepaper) 2024.

Results presented this year reaffirmed the therapeutic potential of APG-2449 in NSCLC, with data demonstrating preliminary efficacy in patients with NSCLC who were TKI naïve and resistant to second-generation ALK TKIs, as well as early antitumor activity in brain metastases. Biomarker analysis showed that, in patients with NSCLC resistant to second-generation ALK TKIs, phosphorylated FAK (pFAK) expression levels in tumor tissue at baseline and reduction in pFAK levels in peripheral blood mononuclear cells (PBMCs) were correlated with responses to APG-2449.

"APG-2449 is an effective multitargeted inhibitor that acts on FAK/ALK/ROS1. Compared to the data released at last year’s ASCO (Free ASCO Whitepaper) Annual Meeting, the latest results presented this year continued to show manageable safety and favorable antitumor activity in patients with NSCLC," said Prof. Li Zhang, the principal investigator of this study from Sun Yat-sen University Cancer Center. "We are very encouraged by the preliminary efficacy observed in patients with resistance to second-generation ALK TKIs, as it suggests that multitargeted inhibition on FAK and ALK may offer a new strategy for the management of patients with NSCLC resistant to second-generation ALK TKIs. We hope that Ascentage Pharma will conduct further studies on APG-2449 and allow more patients to benefit from this novel therapeutic agent as soon as possible."

"These data of APG-2449 in patients with NSCLC revealed a connection between resistance to ALK inhibitors and the FAK pathway, thus suggesting that the multitargeted FAK/ALK/ROS1 TKI APG-2449 may bring renewed hope to patients with NSCLC who are resistant to second-generation ALK inhibitors. This finding is indeed very encouraging," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "Remaining committed to the mission of addressing unmet clinical needs in China and around the world, we will press forward with this clinical development program in order to bring a safe and effective new treatment option to patients in need."

Highlights of these data presented at ASCO (Free ASCO Whitepaper) 2024 are as follows:

Updated study results of novel FAK/ALK/ROS1 inhibitor APG-2449 in patients (pts) with non-small-cell lung cancer (NSCLC) resistant to second-generation ALK inhibitors.

Abstract#: 3124

Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Date and Time: June 1, 2024, Saturday, 9:00 AM – 12:00 PM (Central Time)

First Author: Yuxiang Ma, MD, PhD, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.

Highlights:

Background: ALK inhibitors increase FAK pathway gene expression in ALK+ NSCLC cell lines, with the highest induced expression in drug-tolerant persister cells. This suggests that FAK pathway activation is involved in the mechanism that leads to ALK TKI resistance in ALK+ NSCLC. APG-2449 is an orally active FAK inhibitor and a third-generation ALK/ROS1 TKI that has shown potent antitumor activity in preclinical models. This poster reports further safety and efficacy data of APG-2449.

Patient enrollment and methods:

This study comprises dose-escalation and dose-expansion portions. 1,200 mg daily (QD) was determined as the RP2D. There were two cohorts in the dose-expansion portion: Cohort 1 included patients with NSCLC who were resistant to second-generation ALK TKIs; Cohort 2 included patients with NSCLC who were ALK or ROS1 TKI naïve.
As of April 2, 2024, a total of 144 patients with NSCLC, mesothelioma, or ovarian cancer were treated with APG-2449 at doses ranging from 150 – 1,500 mg. The median (range) age of patients was 53 (21-78) years, and 53.5% were female.
Efficacy results:

The ORRs of APG-2449 in patients with ROS1+ and ALK+ TKI-naïve NSCLC (n=36) were 68.2% (15/22) and 78.6% (11/14), respectively. Of the 22 patients with NSCLC resistant to second-generation ALK inhibitors and without targetable bypass gene mutations (e.g., KRAS G12C, BRAF V600E), 10 achieved PRs (10/22; 45.5%). Among the patients treated at RP2D, 12 had brain metastasis at baseline, 9 of whom achieved intracranial PR, resulting in an intracranial ORR of 75.0%.
Biomarker analysis found that, in patients with NSCLC that was resistant to second-generation ALK TKIs, responses to APG-2449 were correlated with pFAK levels in tumor tissues at baseline and reductions in pFAK levels in PBMCs.
Safety results: A total of 129 (89.6%) patients had treatment‑related adverse events (TRAEs), the most frequent (≥10%) of which were elevated serum creatinine (49.3%), increase in alanine aminotransferase (42.4%), increase in aspartate aminotransferase (36.1%); nausea (28.5%); vomiting (23.6%); diarrhea (22.9%); decreased leukocyte count (22.2%), decreased neutrophil count (17.4%) and rash (13.2%). In all, 20 (13.9%) TRAEs were grade ≥ 3.

Conclusions: APG-2449 demonstrated preliminary efficacy in patients with NSCLC whose disease was TKI naïve and resistant to second-generation ALK inhibitors, especially in brain metastases. Biomarker analysis showed that, in patients with NSCLC resistant to second-generation ALK TKIs, responses to APG-2449 PFS were correlated with pFAK levels in tumor tissues at baseline and reductions in pFAK levels in PBMCs.

*APG-2449 is an investigational drug that has not been approved in any country and region.

Appendix: The four clinical studies of Ascentage Pharma’s three drug candidates, including lisaftoclax, presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting.

Drug Candidates

Abstract Title

Abstract #

Format

Olverembatinib
(HQP1351)

Updated efficacy results of
olverembatinib (HQP1351) in patients
withtyrosinekinase inhibitor (TKI)-
resistantsuccinatedehydrogenas
e (SDH)-deficientgastrointestinal
stromal tumor (GIST)and
paraganglioma

#11502

Oral
Report

Lisaftoclax
(APG-2575）

Safety and efficacy of lisaftoclax, a
novel BCL-2 inhibitor, in combination
withazacitidine in patients with
treatment-naïve or relapsed
or refractory acute myeloid leukemia

#6541

Poster
Presentation

Updated efficacy and safety results of
BCL-2 inhibitorlisaftoclax (APG-2575)
alone or combinedwithibrutinibor
rituximab in patients (pts)with
Waldenströmmacroglobulinemia
(WM)

#7078

Poster
Presentation

APG-2449

Updated study results of novel
FAK/ALK/ROS1 inhibitor APG-2449 in
patients (pts) with non-small-cell lung
cancer (NSCLC) resistant tosecond-
generationALK inhibitors

#3124

Poster
Presentation

On June 1, 2024 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company pioneering the design and development of a new class of custom-built protein drugs known as DARPin therapeutics, reported it had presented the final data from its Phase 1 dose-escalation study of MP0317 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2024, held in Chicago, IL, USA (Press release, Molecular Partners, JUN 1, 2024, View Source [SID1234643939]). MP0317 is a CD40 agonist designed to activate immune cells specifically within the tumor microenvironment (TME) by anchoring to fibroblast activation protein (FAP) which is expressed in high amounts around tumors. This tumor-localized approach has the potential to deliver greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.

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"The Phase 1 data for MP0317 demonstrate the ability of the FAP x CD40 DARPin to avoid the systemic toxicities of CD40 agonists while showcasing truly promising modulation of the tumor microenvironment," said Philippe Legenne, MD, MBA, Molecular Partners’ acting Chief Medical Officer. "This further deepens the clinical evidence supporting DARPins’ ability to deliver multi-specific candidates with enhanced capabilities in oncology including localized activation of powerful immunostimulatory molecules. We will continue discussions with potential partners towards clinical evaluation of MP0317 in combination with complementary approaches."

Mechanistic data & clinical response
The final analysis of this phase 1 dose-escalation study included 46 patients with advanced solid tumors and confirms earlier reported interim analysis findings. MP0317 treatment resulted in target occupancy in tumor biopsies with evidence of TME remodeling as characterized by increases in dendritic cells (DC), T follicular helper cells and plasma cells, as well as IFNγ downstream activation and DC maturation gene signature score increases. These findings were further supported by observed elevation of serum levels of CXCL10, a pro-inflammatory downstream effector of the IFNγ signaling.

In terms of clinical response, one patient achieved an unconfirmed partial response and stable disease was observed in 14 additional patients. The data support further clinical evaluation of MP0317 in combination with complementary anticancer therapies. Dose-response analyses of the final trial data propose MP0317 at dosages of 1.5mg/kg or above as providing an optimal benefit-risk profile, with adjustable dosing frequency to match a combination dosing scheme.

Safety & tolerability
MP0317 displayed a favorable and manageable safety profile across all nine planned dosing cohorts (0.03–10 mg/kg administered intravenously weekly (Q1W) or every 3 weeks (Q3W). The most frequently observed adverse reactions were fatigue and lower grade infusion-related reactions (grade 1–2). Dose-limiting toxicity was reported in one patient (transient asymptomatic grade 3 elevation of liver enzymes) at the highest planned dose of 10 mg/kg administered Q3W.

Details of the poster presenting the final results from the MP0317 Phase 1 study at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting can be found below. The poster will be made available on Molecular Partners’ website after the presentation.

Title: Effect of MP0317, a FAP x CD40 DARPin, on safety profile and tumor-localized CD40 activation in a phase 1 study in patients with advanced solid tumors

Abstract number (poster board): 2573 (52)

Timing: 1 June 2024; 9:00 am – 12:00 pm PST