P=N/A, N=13, Active, not recruiting, Fundació Sant Joan de Déu | Recruiting --> Active, not recruiting | Phase classification: P1 --> PN/A | Trial completion date: Jun 2022 --> Jul 2024 | Trial primary completion date: Jun 2022 --> Jun 2024

P3, N=15, Active, not recruiting, Takeda | Recruiting --> Active, not recruiting | N=10 --> 15

P1/2, N=126, Completed, SWOG Cancer Research Network | Active, not recruiting --> Completed

P2, N=96, Recruiting, Theriva Biologics SL | Phase classification: P2b --> P2

We have evaluated dextran-enhanced CEST MRI’s ability to assess tumor responses to stroma-targeting therapy. Our data indicates that 10 kD dextran is suitable for monitoring the tumor responses to PEGPH20. Reference : 1.

Conclusions Encouraging survival was observed in patients progressing to anti-PD(L)-1 agents after systemic VCN-01 with Durvalumab. VCN-01-induced upregulation of PD-L1, which correlated with enhanced patient survival.

Our results suggest that k derived from SSM and V from ETM, both using group AIF, are optimal for the detection of microvascular changes induced by stroma-directed drug PEGPH20. These analyses provide insights in the choice of PK model and AIF for optimal DCE protocol design in mouse pancreatic cancer models.

P=N/A, N=110, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2023 --> Oct 2024 | Trial primary completion date: Oct 2023 --> Oct 2024

Treatment of MDA-MB-231 LM2-4 tumours reduced ADC and dramatically increased tumour viscoelasticity measured by MR elastography. Correlation matrix analyses of data from all models identified ADC as having the strongest correlation with HA accumulation, suggesting that ADC is the most sensitive imaging biomarker of tumour response to PEGPH20.

Atezolizumab plus PEGPH20 showed limited clinical activity in patients with PDAC and none in patients with GC. The safety of atezolizumab plus PEGPH20 was consistent with each agent's known safety profile. (ClinicalTrials.gov Identifier: NCT03193190 and NCT03281369).

DCAF at diagnosis of advanced BTC can stratify patients who have worse outcomes when treated with upfront platinum-based chemotherapy. Each increase in %ctDNA decreases survival probabilities.

PEGPH20 may be useful for radiosensitization of pancreatic cancer but only in the subset of tumors with substantial hyaluronan accumulation. The response of the treatment may potentially be monitored by non-invasive imaging of the hemodynamic and metabolic changes in the tumor microenvironment.

P1/2, N=290, Recruiting, Hoffmann-La Roche | Active, not recruiting --> Recruiting

Treatment with VCN-01 is feasible and has an acceptable safety. Encouraging biological and clinical activity was observed when administered in combination with nab-paclitaxel plus gemcitabine to patients with pancreatic adenocarcinoma.

P1/2, N=410, Recruiting, Hoffmann-La Roche | Trial primary completion date: Feb 2025 --> Aug 2024

P1, N=13, Recruiting, Fundació Sant Joan de Déu | Trial completion date: Apr 2021 --> Jun 2022 | Trial primary completion date: Sep 2020 --> Jun 2022

P1, N=20, Active, not recruiting, Institut Català d'Oncologia | Recruiting --> Active, not recruiting | Trial completion date: Dec 2021 --> Jan 2023 | Trial primary completion date: Sep 2021 --> Jan 2023

PEGPH20 enhanced treatment effect of radiation therapy. The results validated the utility of the imaging methods to non-invasively monitor the changes in TME and predicted the radiosensitizing effect of hyaluronan depletion.

VCN-01 is an oncolytic adenovirus with direct antitumor effects and stromal disruption capabilities, representing a new therapeutic agent for cancers with dense stroma.

P1/2, N=290, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Nov 2022 --> Jun 2024 | Trial primary completion date: Nov 2022 --> Jun 2024

Remodelling the stroma of HA-rich tumours by depletion of HA with PEGPH20 pre-treatment, is a potentially successful strategy to improve the intra-tumour distribution of anticancer drugs, increasing their therapeutic efficacy, without increasing toxicity.

P1/2, N=290, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1/2, N=410, Recruiting, Hoffmann-La Roche | Trial completion date: Feb 2023 --> Feb 2025 | Trial primary completion date: Feb 2023 --> Feb 2025

P1/2, N=290, Recruiting, Hoffmann-La Roche | Trial completion date: Nov 2021 --> Nov 2022 | Trial primary completion date: Nov 2021 --> Nov 2022

The C3M/PRO-C3 ratio measuring type III collagen turnover in plasma has potential as a blood-based predictive biomarker in patients with mPDA and provides additional value to a HA biopsy when applied for patient selection.

P1b/2, N=25, Terminated, Eisai Inc. | N=14 --> 25 | Active, not recruiting --> Terminated; evolving standard of care and difficulties of enrolling participants

[F]-FAC PET was shown to be a good surrogate for gemcitabine uptake, and when combined with MR, to successfully determine drug uptake in tumors growing in the pancreas. PEGPH20 had moderate effects on tumor uptake of gemcitabine.

P1/2, N=410, Recruiting, Hoffmann-La Roche | Trial completion date: Nov 2021 --> Feb 2023 | Trial primary completion date: Nov 2021 --> Feb 2023

Stromal degradation of hyaluronan via PEGPH20 in combination with FAKi and anti-PD-1 antibody further depletes immunosuppressive cells in the TME including G-MDSCs, inflammatory resident monocytes and PD-L1 expressing myeloid cells, and appears to target the CXCR4 pathway through PEGPH20. These findings support testing the combination of FAKi and anti-PD-1 antibody with agents targeting CXCR4 directly or indirectly by PEGPH20 in human PDAC.

Herein, we develop a reduction/oxidation- responsive hierarchical nanoparticles coencapsulating paclitaxel (PTX) and pH-stimulated hyaluronidase (pSH) to surmount the sequential biological barriers for precise cancer therapy...Within the acidic tumor microenvironment (TME), pSH would be partially reactivated to decompose the dense tumor extracellular matrix (ECM) for deep tumor penetration. Interestingly, PTX/pSH-PHSS could be degraded apace by the completely activated pSH within endo/lysosomes and the intracellular redox microenvironment to facilitate drug release to produce the highest tumor inhibition (93.71%) in breast cancer models.

P1/2; Trial completion date: Feb 2022 --> Nov 2021 | Trial primary completion date: Feb 2022 --> Nov 2021

P2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=15 --> 0 | Not yet recruiting --> Withdrawn

P1, N=13, Recruiting, Fundació Sant Joan de Déu | Trial completion date: Nov 2019 --> Apr 2021 | Trial primary completion date: Sep 2019 --> Sep 2020

The treatment caused local vitreous inflammation but no systemic complications. Thus, oncolytic adenoviruses targeting RB1 might provide a tumor-selective and chemotherapy-independent treatment option for retinoblastoma.

Based on this, stromal modifying agent such as Pegvorhyaluronidase alfa (PEGPH20) was developed and investigated in phase I-III studies...It is also important to consider that although the tumor stroma may be a physical barrier hampering drug delivery, it may also have protective effects in restraining tumor growth and progression. Further studies in molecular biology to better characterize the complex interaction between the microenvironment and cancer cells are warranted.

P2, N=15, Not yet recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2021 --> Oct 2022 | Initiation date: Oct 2019 --> Feb 2020 | Trial primary completion date: Oct 2020 --> Oct 2022

P1/2; Trial completion date: Sep 2020 --> Feb 2022 | Trial primary completion date: Nov 2019 --> Feb 2022

P1b, N=85, Terminated, Halozyme Therapeutics | Trial completion date: Mar 2021 --> Nov 2019 | Recruiting --> Terminated | Trial primary completion date: Oct 2020 --> Nov 2019; Sponsor decision

Funding: VCN Biosciences, AstraZeneca. Clinical trial identification: NCT03799744.

P1/2; Trial completion date: Apr 2020 --> Sep 2020