P1/2, N=612, Recruiting, Regeneron Pharmaceuticals | N=326 --> 612 | Trial primary completion date: Jan 2027 --> Apr 2027

The mechanism of action of huAR9.6 may depend on dense avid binding to homologous SEA domains on MUC16. The results of this study validate the translational therapeutic potential of huAR9.6 against MUC16-positive PDACs.

In the 97 EOC patients after optimal debulking surgery (residual tumor <1 cm or no gross residual tumor), patients treated with CIT had a dramatical and statistically significant improvement of both progression-free survival (PFS) and overall survival (OS) compared to those treated with chemotherapy alone with a median PFS of 41.8 months versus 12.2 months (hazard ratio &lsqb;HR] 0.46, 95 % confidence interval &lsqb;CI] 0.28-0.7) and OS not yet been reached (NE) versus 42.3 months (HR 0.35, 95 % CI 0.16-0.74), respectively. The current review as Part II will explore the possibility of using CIT as front-line therapy in the management of advanced-stage EOC patients after maximal cytoreductive surgery based on the evidence by many phase 2 studies.

P1/2, N=690, Recruiting, Regeneron Pharmaceuticals | Trial completion date: Jul 2024 --> Jun 2026 | Trial primary completion date: Jul 2024 --> Jun 2026

The current standard therapy of epithelial ovarian cancer (EOC) is the combination of surgery (primary cytoreductive surgery or interval cytoreductive surgery) and platinum-based chemotherapy (mainly using paclitaxel and carboplatin either by neoadjuvant chemotherapy and/or by postoperative adjuvant chemotherapy) with/without adding targeted therapy (mainly using anti-angiogenesis agent- bevacizumab)...It is well-known that overexpression of CA125 has been associated with attenuated cellular apoptosis, platinum chemotherapy resistance, tumor proliferation and disease progression, suggesting that anti-CA125 may play a role in the management of patients with EOC. The current review is a Part I which will focus on development of anti-CA125 monoclonal antibody, hoping that alternation of the front-line therapy by chemo-immunotherapy will be beneficial for prolonged survival of patients with EOC.

Conclusion/Implications Ubamatamab +/- cemiplimab demonstrated acceptable safety and evidence of clinical activity in heavily pretreated OC. An ongoing randomised Phase 2 study is evaluating ubamatamab alone and with cemiplimab.

The impact of ubamatamab on QOL and physical functioning will be assessed. Current Trial Status: The study is currently recruiting patients to combination dose escalation, monotherapy dose expansion, and the randomized Phase 2 cohort.

The primary objective is PFS determined by RECIST 1.1 criteria. Current Trial Status: At the time of abstract submission, 618 patients were enrolled and target enrolment Cohort 1 (378) and Cohort 2 (240) was achieved.

P1b/2, N=54, Recruiting, CanariaBio Inc. | Trial primary completion date: Apr 2023 --> Apr 2024

P2, N=10, Active, not recruiting, CanariaBio Inc. | Trial completion date: May 2024 --> Oct 2024 | Trial primary completion date: Sep 2023 --> Jan 2024

P2, N=10, Active, not recruiting, CanariaBio Inc. | Recruiting --> Active, not recruiting | Trial completion date: May 2023 --> May 2024 | Trial primary completion date: May 2023 --> Sep 2023

P3, N=615, Active, not recruiting, CanariaBio Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2024 --> Sep 2025

P1/2, N=468, Recruiting, Nanjing Leads Biolabs Co.,Ltd | Not yet recruiting --> Recruiting

LBL-033, a novel bispecific antibody targeting CD3 and MUC16 with a unique epitope, which is located at the MUC16 membrane-proximal domain, with affinity differentiation between anti-MUC16 and anti-CD3. It is shown a great anti-tumor efficacy in animal models, with a good safety profile in monkeys. These data support LBL-033 as a novel therapeutic bispecific antibody for ovarian cancer and other MUC16 positive tumors.

No abstract available

P1b/2, N=54, Recruiting, CanariaBio Inc. | Trial primary completion date: Dec 2021 --> Apr 2023

Patients were assigned to one of the followings: Cohort 1 (prior 1-3 lines of therapy), PLD (40 mg/m2 q4w till PD) + Oregovomab 2 mg (C1,2,3,5,7 for 5 doses) or Cohort 2 (>3 prior lines of therapy), weekly paclitaxel (80 mg/m2 D1,8,15 q4w till PD) + Oregovomab 2 mg (C1,2,3,5,7 for 5 doses). Trial in progress: there are no available results at the time of submission.

Trial in progress: there are no available conclusions at time of submission.

MUC16 expression is a frequent feature in epithelioid sarcoma and may be identified in other INI-1-deficient malignancies. MUC16 is a possible therapeutic target and warrants further clinical trial development outside the ovarian cancer field.

Exclusion criteria include recent biologic therapy (7 days); approved conventional therapy (except biologics or immunotherapy) <3 weeks (wks) or investigational agents <4 wks prior to first study dose; and anti–PD-L1 therapy <5 T 1/2 prior to first study dose. Key exploratory endpoints are correlation between clinical efficacy endpoints and baseline protein expression levels of MUC16 and PD-L1. Results and Discussions NA Conclusion NA

P2, N=10, Recruiting, OncoQuest Pharmaceuticals Inc. | Not yet recruiting --> Recruiting

P2, N=10, Not yet recruiting, OncoQuest Pharmaceuticals Inc.

P1/2, N=31, Recruiting, National Cancer Centre, Singapore | Active, not recruiting --> Recruiting

Overall, we conclude that KDM6A mutation is frequent in BC and promotes tumour immune escape, which may serve as a novel biomarker to predict the immune response.

Conclusion Multimodal sequencing analysis of CTC gDNA and cfDNA was feasible and revealed additive variant information in both fractions –despite not exclusively detecting tumor-specific variants, but also germline variants. Consequently, it is advised to assess CTC gDNA and cfDNA variants to deconvolute a comprehensive genomic picture.

Conclusion Multimodal sequencing analysis of CTC gDNA and cfDNA was feasible and revealed additive variant information in both fractions –despite not exclusively detecting tumor-specific variants, but also germline variants. Consequently, it is advised to assess CTC gDNA and cfDNA variants to deconvolute a comprehensive genomic picture.

Conclusion Multimodal sequencing analysis of CTC gDNA and cfDNA was feasible and revealed additive variant information in both fractions –despite not exclusively detecting tumor-specific variants, but also germline variants. Consequently, it is advised to assess CTC gDNA and cfDNA variants to deconvolute a comprehensive genomic picture.

Conclusion Multimodal sequencing analysis of CTC gDNA and cfDNA was feasible and revealed additive variant information in both fractions –despite not exclusively detecting tumor-specific variants, but also germline variants. Consequently, it is advised to assess CTC gDNA and cfDNA variants to deconvolute a comprehensive genomic picture.

Most importantly, we found that most of those variants were insertions (frameshift insertions) and deletions (frameshift deletions and in-frame deletions), such as insertion variants in ACVR2A, PCLO, and TBCK; such mutations were detected in almost 95% of patients. Our study demonstrated that the targeted NGS-based ctDNA mutation profiling was a useful tool for hepatocellular carcinoma (HCC) monitoring and could potentially be used to guide treatment decisions in HCC.

MUC16 contributes to the development and progression of CRC by binding to JAK2, thereby promoting phosphorylation of JAK2 and further activating STAT3 phosphorylation.

CA125 represents a significant and independent prognostic factor in CRC patients, superior to CEA. Furthermore, CA242 served as a better prognostic marker than both CEA and CA19-9. We recommend including both CA125 and CA242 in prognostic clinical trials among CRC patients.

Patients with high preoperative serum CA125 and AFP levels exhibited the worst prognosis (low DFS and OS rates). In conclusion, high baseline CA125 levels may be associated with a poor prognosis in patients with HBV-related HCC.

Our findings imply that shared and private mutations significantly contribute to the complexity of differential gene expression and pathway interaction and might explain the clonal evolution of different molecular renal cancer subgroups. Multi-regional sequencing is central for the identification of subclones within ccRCC.

Higher mutation rates of immune response genes (e.g., TP53 and MUC16) were also observed in the low-risk subtype (both P < 0.05). Discovery of the HCC low-risk subtype might provide clues for HCC prognosis and immunotherapy prediction.

However, the combination of BiTEDs with anti-VEGF was superior to combination with anti-PD1, based on findings of decreased peritoneal tumor burden and ascites with the former. This study shows the feasibility and efficacy of MUC16- specific BiTEDs and provides a basis for the combination with anti-VEGF therapy for ovarian cancer.

There was no correlation between the PBMC-bound and serum levels of CA125, suggesting that these two compartments are not in stoichiometric equilibrium. Understanding where and how subset-specific cell-bound surface CA125 takes place may provide guidance towards a new diagnostic biomarker in ovarian cancer.

Exclusion criteria include recent biologic therapy ( 7 days); approved conventional therapy (except biologics or immunotherapy) < 3 weeks (wks) or investigational agents < 4 wks prior to first study dose; and anti–PD-L1 therapy < 5 half-lives prior to first study dose . In expansion, primary endpoint is ORR by RECIST 1.1 for each combination; key secondary endpoints are TEAEs, serious AEs, deaths . Key exploratory endpoints are correlation between clinical efficacy endpoints and baseline protein expression levels of MUC16 and PD-L1.

In the present multi-scale radiogenomic analysis of ccRCC, radiomics played a central role. Radiomic subtypes could help discern genomic alterations and non-invasively stratify ccRCC patients.

LMS has a complex genetic background, with multiple CNA and mutations affecting genes implicated in tumorigenesis. We identified several molecular changes with potential impact on survival of LMS patients when treated with eribulin.

However, as OC is heterogenic in its nature with high mutation diversity and overexpression of different receptors, there is a need to consider an individual approach to treat this type of cancer. In this publication, we would like to present the history and status of therapies involving the CAR T cells in treatment of OC tumours, suggest potential T cell-intrinsic determinants of response and resistance as well as present extrinsic factors impacting the success of this approach.

This study confirms previous observations that AL cannot be defined by a singular or a set of well- defined genetic events, and locate AL in the crossroad between MGUS and MM also in genetic grounds. Our results also provide new immunophenotypic markers that could emerge as novel risk-markers for AL in patients with monoclonal gammopathies.

The different mutated genes are related to the NF-κB and JAK-STAT pathways, and the different pathogenetic mechanisms leading to the development of DLBCL may be influenced by the tissue microenvironment. Differences in genetic alterations might influence the clinicopathological characteristics of GI-DLBCL.