P2, N=132, Not yet recruiting, Roswell Park Cancer Institute | Initiation date: Apr 2024 --> Jul 2024

The continuous treatment of U937 cells with the benzene metabolite hydroquinone (HQ) generated U937/HQ cells, exhibiting enhanced responsiveness to the cytotoxic effects of ONC212...Collectively, our data suggested that ONC212 upregulated SLC35F2 expression and triggered NOXA-mediated MCL1 degradation in U937, U937/HQ, and HL-60 cells by activating the AKT/NOX4/HuR/ATF4 pathway. The ONC212-induced signaling pathway showed anti-AML activity and enhanced YM155 cytotoxicity.

P2, N=66, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Dec 2023 --> Dec 2024

P2, N=247, Active, not recruiting, MimiVax, LLC | Recruiting --> Active, not recruiting

MX106-4C selectively kills ABCB1-positive MDR colorectal cancer cells via a novel ABCB1-dependent survivin inhibition mechanism, providing a clue for designing CS compound as an alternative strategy to overcome ABCB1-mediated colorectal cancer MDR.

P1, N=6, Active, not recruiting, Providence Health & Services | Trial primary completion date: Nov 2023 --> Jun 2023

P2, N=47, Active, not recruiting, University Health Network, Toronto | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=84, Not yet recruiting, Roswell Park Cancer Institute

P1, N=36, Not yet recruiting, NexImmune Inc. | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Jul 2024 --> Jul 2026

P2, N=132, Not yet recruiting, Roswell Park Cancer Institute

P1, N=14, Recruiting, Roswell Park Cancer Institute | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

Further biological studies revealed that compound AQIM-I significantly inhibited survivin expression and colony formation and induced ROS production, apoptosis, cell cycle arrest, DNA damage, and autophagy. Furthermore, the promoter-luciferase reporter assay showed that AQIM-I attenuated the survivin promoter activity enhanced by the overexpression of ILF3/NF110 in a concentration-dependent manner, and specific binding (K = 163 nM) of AQIM-I to ILF3/NF110 was detected by surface plasmon resonance.

Our data demonstrated that the synergistic cytotoxicity of DAC and YM155 in AML cell lines U937 and HL-60 is dependent on AKT- and p38 MAPK-mediated upregulation of SLC35F2 and p38 MAPK-mediated degradation of survivin and MCL1. This indicates that a treatment regimen that amalgamates YM155 and DAC may be beneficial for AML.

BOTs were screened 24h and 48h after printing with proteosome inhibitor Bortezomib and survivin inhibitor YM-155... Functional high-throughput ex vivo DRP technologies have the potential to transform cancer treatment – from bench to bedside – along the drug discovery to market roadmap for much needed novel anticancer agents.

In addition to small molecules, several survivin peptide vaccines are currently under development...Overall, survivin is a promising cancer drug target. However, challenges still need to be addressed before the survivin targeted therapies can be widely used in the clinics.

An earlier study has shown that YM155 enhances daratumumab-mediated cellular lysis of multiple myeloma cells. Our RNAseq and CyTOF results thus suggest a potential basis of synergy between YM155 with immunotherapies approved for myeloma, which we will test further. Our approach thus integrates in silico prediction with single-cell multi-ome analysis to identify molecular mechanisms potentially underlying subclonal response to novel combination therapy candidates (secDrugs) for the treatment of RRMM.

Introduction: The SPiReL phase II clinical trial evaluated combination immunotherapy with an immunogenic vaccine formulation to the tumor antigen survivin comprised of maveropepimut-S (MVP-S), pembrolizumab and cyclophosphamide in survivin-expressing relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL). The mean and median percentage of survivin-positive tumor cells for all enrolled participants (n= 25) was 91% and 99%, respectively. At the per participant level, the range of survivin expression was 50-100% of the cellular content. The heterogeneity of survivin expression intensity among participants is shown in Figure 1.

Our findings revealed that ZWZ-3 could downregulate BIRC5 and inhibit melanoma proliferation and metastasis through the β-catenin/HIF-1α/VEGF/MMPs pathway. Therefore, BIRC5 represents a promising therapeutic target for the treatment of melanoma.

In this study, we present updated findings from a phase 2 clinical trial (NCT02078648) evaluating SL-701+poly-ICLC+bevacizumab, where the 12-month overall survival (OS) was 50%. These qualitative differences in the immune response, detectable as early as week 8 post treatment, may serve as biomarkers for monitoring and predicting survival. Deep sequencing of SL-701-specific T-cells is planned.

We hypothesized that these differences may contribute to impaired anti-cancer immune responses in aged mice and therefore assessed the anti-tumor efficacy of different IO therapies in aged mice, including both co-stimulation (using an anti-OX40 antibody) and immune checkpoint blockade (using anti-PD-L1 and anti-CTLA-4 antibodies). Whilst aged mice retained the capacity to generate anti-tumor immune responses, these were significantly attenuated when compared to the responses observed in young mice. These differences highlight the importance of age-related immunological changes in assessing and refining the translational insights gained from preclinical mouse models.

Our findings have unraveled that BIRC5 holds promise as a novel biomarker and therapeutic target for lung adenocarcinoma. Additionally, we have discovered a novel pathway in which BIRC5 inhibition can induce pyroptosis through the caspase3-GSDME pathway in lung adenocarcinoma cells.

We used a CAR-T cell consisting of a CD33 binder and CD28z-OX40 costimulatory moiety...2). Our work provides critical information to overcome resistance to CAR-T cell treatment by neutralising the negative effects of the stromal microenvironment.

PC-002 (also known as Sepantronium Bromide, or SepB) is a small molecule previously identified as a survivin suppressant with antitumor activity against a range of tumor types... At the time of abstract submission, the 1st cohort (3.6 mg/m2/day) of 3 patients have completed at least four cycles of treatment. PC-002 is generally well-tolerated at 3.6 mg/m2/day and progression to Cohort 2 at a dose of 4.8 mg/m2/ day was approved by the Safety Review Committee. Two patients with relapsed/refractory Burkitt Lymphoma at the starting dose of 3.6 mg/m2/day achieved a confirmed PR.

P1/2, N=73, Active, not recruiting, PDC*line Pharma SAS | Recruiting --> Active, not recruiting | Trial completion date: Sep 2025 --> Dec 2025 | Trial primary completion date: Sep 2025 --> Dec 2025

RESULTS69 patients have been enrolled as of April 11, 2023. CONCLUSIONFindings from this trial will demonstrate the safety and efficacy of survivin vaccine in GBM (Clinical trial information: NCT05163080).

P1/2, N=64, Recruiting, PDC*line Pharma SAS | Trial completion date: Aug 2024 --> Sep 2025 | Trial primary completion date: Aug 2024 --> Sep 2025

We also provide new data showing that FL118, a molecular glue DDX5 degrader, selectively works against current treatment-resistant prostate cancer organoids/cells. Altogether, current studies demonstrate that DDX5 may represent a unique oncotarget for effectively conquering cancer with minimal toxicity to normal tissues.

P1, N=6, Active, not recruiting, Providence Health & Services | Recruiting --> Active, not recruiting | N=18 --> 6 | Trial completion date: Jun 2026 --> Sep 2026 | Trial primary completion date: Jun 2023 --> Sep 2023

Consistent with the expression profile of survivin across a broad range of both hematological and solid tumors, treatment of AML and NSCLC cell lines with ABBV-184 results in T cell activation, proliferation, and potent redirected cytotoxicity of HLA-A2 positive target cell lines, both in vitro and in vivo, including patient-derived AML samples. These results indicate that ABBV-184 is an attractive clinical candidate for the treatment of patients with AML and NSCLC.

P2, N=25, Completed, Sunnybrook Health Sciences Centre | Active, not recruiting --> Completed

This immunotherapy combination was found to be active and safe in this clinically challenging patient population.

PSMD3 collectively regulated the stability of ILF3 protein and facilitated the ubiquitination of endogenous ILF3 in LC, which ultimately promoted the progression of LC cells. The PSMD3/ ILF3 axis could potentially be used as a novel strategy for both diagnosis and treatment of LC.

P1, N=44, Recruiting, Baylor College of Medicine | Trial primary completion date: Apr 2023 --> Apr 2024

P1, N=11, Terminated, Mana Therapeutics | N=27 --> 11 | Active, not recruiting --> Terminated; Product manufacturing

P2, N=47, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | Trial primary completion date: Feb 2023 --> Dec 2023

P1, N=18, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Nov 2023 --> May 2026 | Trial primary completion date: Apr 2023 --> Sep 2022

PC-002 (also known as Sepantronium Bromide, SepB) is a small molecule survivin suppressant with antitumor activity against a variety of tumor types...At the time of abstract submission, the 1 st cohort of 3 patients have completed at least two cycles of dosing. PC- 002 is generally well-tolerated at 3.6 mg/m 2 /day and has been cleared by SRC to the next cohort of RP2D at 4.8 mg/m 2 / day. Preliminary assessment by image analysis showed partial response in 2 pts with relapsed/refractory Burkitt Lymphoma at the starting dose of 3.6 mg/m 2 /day.

MVP-S with intermittent low-dose CPA is well-tolerated, with clinical benefit for patients with recurrent OvCa. Observed responses are irrespective of the platinum status.

P1/2, N=64, Recruiting, PDC*line Pharma SAS | Trial primary completion date: Aug 2022 --> Aug 2024

In addition, we determine that the survivin-suppressing and apoptosis-inducing activities of YM155 involve its interaction with receptor-interacting protein kinase 2 (RIPK2). In an orthotopic intracranial GBM xenograft model, aYM155 prodrug significantly inhibits brain tumor growth in vivo, which correlates with cell-type selective survivin-based pharmacodynamic effects.