On March 14, 2023 Medivir AB (Nasdaq Stockholm: MVIR), a pharmaceutical company focused on developing innovative treatments for cancer in areas of high unmet medical need, reported that the first patient with hepatocellular carcinoma (HCC) has started treatment in phase 2a with the candidate drug fostroxacitabine bralpamide (fostrox) in combination with Lenvima (Press release, Medivir, MAR 14, 2023, View Source [SID1234628721]).

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!

In Medivir’s ongoing phase 1b/2a study, fostrox is given in combination with two other drugs, either with Lenvima, a tyrosine kinase inhibitor, or with Keytruda, an anti-PD-1 checkpoint inhibitor. The study is an open-label, multicenter study and includes patients with HCC for whom current first- or second-line treatment has proven ineffective or is not tolerable. The phase 1b part of the study evaluates which dose of fostrox is most appropriate for the next phase. This dose is then used in the phase 2a part of the study where safety and signals of efficacy are further evaluated.

The preliminary results from the recently completed phase 1b for fostrox in combination with Lenvima were positive with a good safety and tolerability profile where no dose-limiting toxicity was observed. The recommended dose (RP2D) for fostrox in this combination arm was set at 30 mg.

"It is really exciting that we have been able to start the important expansion phase of the study so quickly, with the first patient now being treated with fostrox and Lenvima in phase 2a. The medical need for a new, effective treatment is immense and so is the interest from both investigators and patients, which is why I believe that the recruitment of patients to this part of the study will be completed swiftly," says Pia Baumann, Chief Medical Officer at Medivir AB.

The results from this study will form the basis for the future development plan for fostrox. A total of up to 30 patients with HCC are planned to be recruited in the study that is being conducted at 14 clinics in Great Britain, Spain and South Korea. In the second combination arm where fostrox is administered together with Keytruda, the phase 1b dose escalation is still ongoing.

For additional information, please contact

Magnus Christensen, CFO, Medivir AB
Telephone: +46 8 5468 3100.
E-mail: [email protected]

About fostrox

Fostrox is a pro-drug designed to selectively treat liver cancers and to minimize side effects. It has the potential to become the first liver-targeted and orally administered drug for patients with HCC and other forms of liver cancer. Fostrox has completed a phase 1b monotherapy study, and a combination study in HCC currently ongoing.

About primary liver cancer

Primary liver cancer is the third leading cause of cancer-related deaths worldwide and hepatocellular carcinoma (HCC) is the most common cancer that arises in the liver. Although existing therapies for advanced HCC can extend the lives of patients, treatment benefits are insufficient and death rates remain high. There are 42,000 patients diagnosed with primary liver cancer per year in the US and current five-year survival is 11 percent. HCC is a heterogeneous disease with diverse etiologies, and lacks defining mutations observed in many other cancers. This has contributed to the lack of success of molecularly targeted agents in HCC. The limited overall benefit, taken together with the poor overall prognosis for patients with intermediate and advanced HCC, results in a large unmet medical need.

On March 14, 2023 Akeso, Inc. (9926.HK) reported patient enrollment has been completed for its pivotal Phase III clinical trial for cadonilimab (PD-1/CTLA-4 bi-specific antibody, AK104), the world’s first approved and marketed dual-immune checkpoint bi-specific antibody drug, for use in combination with chemotherapy as first-line therapy for advanced gastric or gastroesophageal junction cancer (GC/GEJC) (Press release, Akeso Biopharma, MAR 14, 2023, https://www.prnewswire.com/news-releases/patient-enrollment-completed-for-phase-iii-clinical-trial-of-akesos-cadonilimab-in-treatment-of-gastric-cancer-301771264.html [SID1234628720]). This marks a step closer to the launch of cadonilimab for a major indication, after the indication for treatment of cervical cancer has been approved.

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!

This clinical trial represents the world’s first clinical investigation of the bispecific PD-1/CTLA-4 bispecific antibody in combination with chemotherapy for the first-line treatment of gastric cancer. A total of 610 subjects are enrolled and the primary study endpoint is to compare the OS of AK104 in combination with a XELOX regimen versus a placebo in combination with XELOX regimen in the intent-to-treat (ITT) population. The interim analysis is expected to be conducted by the end of 2023.

Several phase III studies have been conducted internationally to demonstrate the synergistic effect of immune checkpoint inhibitors in combination with chemotherapy in the treatment of GC/GEJC. Although the combination of anti-PD-1 and anti-CTLA-4 agents has a higher response rate compared to monotherapy with PD-1, the combination of single target drugs also has higher toxicities.

Combining the speech delivered by Professor Ji Jiafu, the President of Peking Cancer Hospital, at the 2022 ASCO (Free ASCO Whitepaper)-GI Congress, with the results by the end of 2021, the phase II trial of cadonilimab in combination with chemotherapy in first-line treatment of gastric cancer demonstrates the long-term survival benefit and favorable safety profile in the overall population.

When only 15% of the PD-L1 population had CPS ≥ 5, the ORR reached 68.1% and the DCR reached 92.3%. In the general population, the overall median PFS was 9.2 months and the median OS was 17.08 months, significantly superior to chemotherapy and associated PD-1 therapy.
Cadonilimab remains remarkably effective and safe in patients with low PD-L1 expression. In PD-L1 patients with CPS ≥ 1 and CPS < 1, their median OS was 17.41 months and 14.65 months respectively.
Compared with PD-1 mAb, no new safety signal was found in cadonilimab; which therefore suggests that it is substantially safe.
In June 2022, cadonilimab was approved by NMPA for the treatment of recurrent or metastatic cervical cancer, becoming the world’s first dual-immune checkpoint inhibitor to be granted such approval. Given the positive confirmatory findings of cadonilimab in advanced gastric cancer research, it is anticipated that cadonilimab will overcome existing therapeutic barriers and optimize the treatment of advanced gastric cancer, providing patients with improved survival benefits. Going forward, Akeso will focus its resources in order to speed up the development of Phase III study, as well as make preparations for the eventual product launch.

On March 14, 2023 Cantargia (Cantargia AB) (Nasdaq Stockholm: CANTA) reported that, following positive results in the lead-in phase of the clinical phase Ib/II trial TRIFOUR, the first triple-negative breast cancer (TNBC) patient has initiated treatment with the IL1RAP-binding antibody nadunolimab (CAN04) and chemotherapy in the phase II randomized part of the trial (Press release, Cantargia, MAR 14, 2023, View Source [SID1234628719]). Up to 98 patients may be included in this part and the next milestone, an interim futility analysis of 28 patients, is estimated in Q4 2023.

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!

"We are proud to have started Cantargia’s first randomized trial with nadunolimab, in patients with triple-negative breast cancer, shortly after presenting an early signal of efficacy in this type of patients. This marks good progress as nadunolimab continues to demonstrate potential to make a significant difference in treatment of cancer," said Göran Forsberg, CEO of Cantargia.

The initial dose-escalation stage of TRIFOUR was recently finalized where an acceptable safety and early signs of efficacy were reported for the combination therapy. The preliminary response rate of 50%, including one complete response in 12 patients, indicates an improvement compared to historical control data for chemotherapy alone.

In the open-label phase II stage of TRIFOUR, first or second-line patients with advanced TNBC will be randomized in a 1:1 ratio to either a control arm where the chemotherapy doublet of gemcitabine and carboplatin is given alone, or an investigational therapy arm where nadunolimab is also administered. The primary objective is to investigate antitumor activity. The TRIFOUR trial is conducted in collaboration with the Spanish Breast Cancer Group (GEICAM).

For further information, please contact
Göran Forsberg, CEO
Telephone: +46 (0)46-275 62 60
E-mail: [email protected]

This is information that Cantargia AB is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 11.40 CET on 14 March 2023.

On March 14, 2023 Servier, a global pharmaceutical group, reported that the Phase 3 INDIGO clinical trial investigating vorasidenib in monotherapy for patients with residual or recurrent IDH mutant low-grade glioma met its primary endpoint of progression free survival (PFS) and the key secondary endpoint of time to next intervention (TTNI) (Press release, Servier, MAR 14, 2023, View Source [SID1234628718]). The results of the prespecified interim analysis were both statistically significant and clinically meaningful.

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!

"Therapeutic progress in the low-grade glioma space has been stagnant for decades. The results of the Phase 3 INDIGO trial, meeting both the primary endpoint of progression-free survival and the key secondary endpoint of time to next intervention, presents an opportunity to shift the treatment paradigm for patients with IDH mutant low-grade glioma by potentially delivering the first targeted therapy," said Susan Pandya, M.D., Vice President Clinical Development and Head of Cancer Metabolism Global Development Oncology & Immuno-Oncology, Servier. "We are grateful to the patients, caregivers, investigators and study teams who made this remarkable achievement possible through their participation in the INDIGO clinical trial."

The interim analysis, which was prespecified in the design of the INDIGO trial, demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival and time to next intervention in patients randomized to vorasidenib monotherapy compared to patients randomized to placebo. Patients enrolled in the INDIGO study had residual or recurrent grade 2 oligodendroglioma or astrocytoma with an IDH1 or IDH2 mutation and had undergone surgery as their only treatment for glioma prior to study enrollment. The safety profile of vorasidenib in monotherapy was consistent with previously published data.

"This potential therapeutic breakthrough is yet another concrete proof-point of the success of our oncology strategy, which aims to focus our science on difficult and hard-to-treat cancers such as those where an IDH mutation is present," said Patrick Therasse, M.D. PhD, Vice-President and Head, Late Stage and Life Cycle Management Oncology & Immuno-oncology Therapeutic Area, Servier. "The results from the Phase 3 INDIGO trial offer patients with IDH mutant low-grade glioma potential hope for a new treatment option for the first time in more than 20 years."

The Phase 3 INDIGO trial results will be presented at an upcoming medical meeting.

Due to the accelerated enrollment and interim efficacy analysis outcome, the INDIGO clinical trial is well ahead of schedule. Servier is working to determine filing timelines and adapt the vorasidenib supply capacity.

About the INDIGO Phase 3 Trial
INDIGO is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of vorasidenib to placebo in participants with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment. (NCT04164901).

About Glioma1
Gliomas are tumors that arise from glial or precursor cells within the central nervous system (CNS). The 2021 WHO classification recognizes four general groups of gliomas, one of which is adult-type diffuse gliomas. These diffuse gliomas are the most common primary malignant brain tumors in adults. The pathogenesis and prognosis of these tumors are tightly linked to mutations (or lack thereof) in the metabolic enzyme isocitrate dehydrogenase (IDH), and molecular testing is required for proper diagnosis. As of 2021, adult-type diffuse gliomas are sub-divided into only three categories:

Astrocytoma, IDH-mutant (CNS WHO grades 2-4)
Oligodendroglioma IDH-mutant, 1p19q-codeleted (CNS WHO grades 2-3)
Glioblastoma IDH-wildtype (CNS WHO grade 4)
1 Neuro Oncology. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. View Source Last accessed-3.13.23

Media Contacts:
Group:
Eric Fohlen-Weill
[email protected]

USA:
Nathan Mellor
[email protected]

On March 14, 2023 Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, reported that the U.S. Food and Drug Administration (FDA) cleared the Company to proceed with its Phase 1-2 clinical trial of ST316 for the treatment of solid tumors (Press release, Sapience Therapeutics, MAR 14, 2023, View Source [SID1234628717]). Sapience expects to begin patient dosing in the Phase 1 dose escalation portion of the study in the first half of 2023 to evaluate the safety, clinical activity, pharmacokinetics and pharmacodynamics of ST316.

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!

ST316 is Sapience’s first-in-class β-catenin antagonist. β-catenin is the effector protein of the Wnt signaling pathway, one of the most important oncogenic pathways. Wnt pathway hyperactivity is known to play a role in greater than 50% of solid tumors, in which it is a driver of oncogenesis and immune suppression. Despite this significant role in tumor formation, Wnt-driven tumors have proven difficult to treat due to the critical function of Wnt-signaling in normal physiology and the associated side effects of complete Wnt-blockade. ST316 separates β-catenin’s physiologic and oncogenic activities, enabling treatment of Wnt-driven tumors while keeping normal β-catenin function intact. ST316 suppresses transcription of Wnt target genes regulating oncogenic proliferation, migration, invasion and metastatic potential, as well as genes regulating the immunosuppression of the tumor microenvironment.

"FDA clearance of the ST316 IND is an exciting achievement for Sapience, representing the second therapeutic candidate we discovered to advance into clinical development," said Dr. Barry Kappel, CEO and President of Sapience. "This milestone is the result of our team’s years of commitment to finding solutions to address oncogenic drivers of disease that have proven historically challenging to drug."

Dr. Abi Vainstein-Haras, Sapience’s Chief Medical Officer, added, "As the first peptide antagonist of β-catenin to enter the clinic, we are thrilled to progress ST316 to a Phase 1-2 study in the first half of 2023. In addition to its known involvement in the pathogenesis of several cancers, the Wnt pathway’s role in regulating immune cell infiltration of the tumor microenvironment makes it a compelling therapeutic target. With preclinical studies demonstrating a favorable safety profile and significant anti-tumor activity, we look forward to bringing ST316’s first-in-class approach to targeting Wnt-driven tumors to the cancer community."

The Phase 1 dose-escalation portion of the study is designed as a basket study to enroll patients with tumors likely to harbor abnormalities of the Wnt/β-catenin signaling pathway. The Phase 2 dose-expansion portion of the study will enroll patients in four specific tumor types known to harbor abnormalities of the Wnt/β-catenin signaling pathway, including cholangiocarcinoma, colorectal, triple negative breast and ovarian cancers.

About ST316
ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator BCL9, a complex that drives oncogene expression in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. The interaction between β-catenin and BCL9 has previously been considered an ‘undruggable’ target due to the inability of small molecules to inhibit complex formation and antibodies to gain access to the cytoplasm or nucleus to disrupt the interaction. ST316 contains a cell penetration moiety to allow intracellular access and a domain designed to bind the first armadillo repeat domain of β-catenin, a site utilized by BCL9 but no other β-catenin binding partners. ST316 suppresses transcription of oncogenic Wnt target genes regulating proliferation, migration, invasion and the metastatic potential of tumor cells, as well as genes regulating the immunosuppression of the tumor microenvironment.