P1, N=18, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2024 --> Apr 2025

P2, N=78, Active, not recruiting, Patrick Boland | Trial completion date: Jun 2023 --> Dec 2024 | Trial primary completion date: Jun 2023 --> Mar 2024

P2, N=110, Active, not recruiting, National Cancer Institute (NCI)

These results support the rationale to improve PK and anti-tumor efficacy of IL-15 by increasing local concentrations at the tumor site via conjugation to a TA-MUC1 binding mAb. The tumor-selective expression pattern of TA-MUC1, powerful immune activation and anti-tumor cytotoxicity, long serum half-life and tumor targeting properties, render GT-00AxIL15 a promising candidate for treatment of solid tumors with high medical need, e.g., ovarian, lung and breast cancer.

P1, N=50, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024

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

P1/2, N=8, Terminated, Georgetown University | Active, not recruiting --> Terminated; Study closed due to lack of enrollment.

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

Flow cytometry analysis showed that P. gingivalis successfully reversed the immunosuppressive TME, thereby suppressing OSCC growth. In summary, the findings of the present study indicated that the rational use of P. gingivalis could serve as a promising therapeutic strategy for OSCC.

These findings demonstrate a previously unidentified vitamin D/VDR-MUC1 signaling axis involved in the regulation of gemcitabine resistance in PDA and suggests that combinational therapies that include targeted activation of vitamin D/VDR signaling may improve the outcomes of patients with PDA.

P1, N=50, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2023 --> Dec 2023

P1/2, N=12, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Oct 2021 --> Feb 2023

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

Importantly, targeting MUC1-C inhibits NEPC self-renewal, tumorigenicity and therapeutic resistance. This dependence on MUC1-C extends to other NE carcinomas, such as SCLC and MCC, and identify MUC1-C as a target for the treatment of these aggressive malignancies with the anti-MUC1 agents now under clinical and preclinical development.

These findings indicate that Rab31 is a novel and promising biomarker and potential therapeutic target for diagnosis, treatment and prognosis prediction in STAD patients. Our data not only identifies a novel Rab31/Stat3/MUC-1/Twist1/EMT pathway in STAD metastasis and drug resistance, but it also provides direction for the exploration of novel strategies to predict and treat STAD in the future.

P1/2, N=33, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jul 2023 --> Dec 2023 | Trial primary completion date: Dec 2022 --> Jul 2023

Based on CRISPR-Cas9 library screening, we found that mucin1 (MUC1) is essential for EGFRvIII glioma cell survival and temozolomide (TMZ) resistance...EPIC-1027 disrupted the EGFRvIII-MUC1-C positive feedback loop in vitro and in vivo, inhibited glioma progression, and promoted sensitization to TMZ. In conclusion, we revealed the pivotal role of MUC1-C in stabilizing EGFRvIII in glioblastoma (GBM) and identified a small molecule, EPIC-1027, with great potential in GBMtreatment.

P2, N=23, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=80 --> 23

In conclusion, MUC1 expressing ccRCC is characterized by a particular metabolic reprogramming. The inhibition of MUC1 expression decreases cell motility and viability and improves cisplatin susceptibility, suggesting that this pathway can regulate de novo chemotherapy resistance in ccRCC.

In addition, this tailored smart nanoformulation has been particularly effective in the therapy of triple-negative breast cancer. The online version contains supplementary material available at 10.1007/s10924-022-02654-4.

When we assessed effects of αGlcNAc binding to MUC1, we found that αGlcNAc blocked galectin-3 binding to MUC1, phosphorylation of the MUC1 C-terminus and recruitment of Src and β-catenin to that C-terminus. These results suggest that αGlcNAc regulates cancer cell phenotypes by dampening MUC1 signal transduction.

Our findings provide cellular and molecular mechanisms for the pro-tumorigenic functions of MUC1 in the inflamed colon. Therapeutic strategies to inhibit MUC1 signal transduction warrant consideration for the prevention or therapy of CAC.

A Phase 2, single-arm trial was designed to evaluate CV301 plus atezolizumab as first-line treatment for cisplatin-ineligible advanced urothelial carcinoma (aUC) (Cohort 1) or progressing after platinum chemotherapy (Cohort 2). Patients exhibiting benefit demonstrated T-cell response to CEA and MUC-1. The trial illustrates the challenges in the development of vaccines, which should be guided by robust preclinical data.

P2; Trial primary completion date: Jun 2022 --> Dec 2022

P1/2, N=12, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> May 2024 | Trial primary completion date: Dec 2025 --> Oct 2021

The effectiveness of the Ehrlich ascites solid (EAT) mice treated with Gem-MUC1 inhibitor NPs was higher than that of the animals treated alone. Overall, the combined administration of Gem and MUC1 inhibitor-loaded NPs was found to be more efficacious than Gem and MUC1 inhibitor delivered separately.

Two granulysin (GRNLY) based immunotoxins were generated, one containing the scFv of the SM3 mAb (SM3GRNLY) and the other the scFv of the AR20.5 mAb (AR20.5GRNLY)...Histological studies of tumors obtained from treated mice demonstrated reduced cellularity, nuclear morphology compatible with apoptosis induction and active caspase-3 detection by immunohistochemistry. Overall, our results exemplify that these immunotoxins are potential drugs to treat Tn-expressing cancers.

Overexpression miR-520a-3p inhibited AML cell proliferation, and promoted apoptosis via inhibiting MUC1 expression and repressing Wnt/β-catenin pathway activation.

P2, N=80, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jul 2023 --> Jul 2024

No abstract available

Combination of a TA-MUC1-targeting antibody and an EGFR-targeting antibody is safe and feasible. Interesting antitumor activity was observed in heavily pretreated patients. Future studies should test this combination together with chemotherapy and explore the potential of sTA-MUC1 as a companion biomarker for further development of the combination.

huMNC2-CAR44 T cells completely obliterated a variety of MUC1* positive solid tumors in NSG mice in vivo...Dose escalation is standard 3+3 design with dosing levels ranging from 3.3x10^5 to 1.0x10^7 CAR+ cells/kg, and fludarabine/cyclophosphamide lymphodepletion pre-treatment...Six (6) patients have been enrolled and five (5) patients have been treated to date. Phase II will be comprised of 3 cohorts of 15 patients in each arm of luminal, HER2+ and triple negative breast cancers for a total of 45 patients in Phase II.

P1/2, N=79, Active, not recruiting, ImmunityBio, Inc. | Trial completion date: Jan 2020 --> Jan 2023 | Trial primary completion date: Dec 2019 --> Dec 2022

Our results show that by using TA-MUC1 as a broadly expressed and highly tumor-specific antigen, we are able to direct IL-15 to the tumor. Local enrichment of GT-00A x IL15 within the tumor ultimately induced local effector cell activation and expansion. GT-00A x IL15 showed single agent efficacy in vivo with a good safety profile.

P1/2, N=33, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jul 2022 --> Jul 2023 | Trial primary completion date: Dec 2021 --> Dec 2022

P2; N=78; Active, not recruiting; Sponsor: Kristen Spencer; Trial primary completion date: Dec 2021 --> Jun 2022

P2, N=44, Completed, Transgene | Active, not recruiting --> Completed | Trial completion date: Nov 2020 --> Feb 2021

The immunological interventions were active immunotherapy Bacillus Calmette-Guérin (BCG) adoptive cell transfer (i.e. transfer factor (TF), tumour-infiltrating lymphocytes (TIL), dendritic cell/cytokine-induced killer (DC/CIK), antigen-specific cancer vaccines (melanoma-associated antigen 3 (MAGE-A3) and L-BLP25), and targeted natural killer (NK) cells...Two trials provided health-related quality of life results with contradicting results.  AUTHORS' Based on this updated review, the current literature does not provide evidence that suggests a survival benefit from adding immunotherapy (excluding checkpoint inhibitors) to conventional curative surgery or radiotherapy, for people with localised NSCLC (stages I to III). Several ongoing trials with immune checkpoints inhibitors (PD-1/PD-L1) might bring new insights into the role of immunotherapy for people with stages I to III NSCLC.

P2, N=80, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting | N=14 --> 80

Gatipotuzumab switch maintenance therapy does not improve outcome in TA-MUC1-positive ovarian cancer patients.