citoplurikin (IRX-2)

P1; Trial completion date: Jan 2023 --> May 2024

P1, N=8, Active, not recruiting, City of Hope Medical Center | Phase classification: P1b --> P1 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=19, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2023 --> Dec 2024

P1, N=19, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Phase classification: P1b --> P1

Subjects with stage II-III TNBC were randomized 1:1 (n=12) to receive induction pembrolizumab (200mg IV) +/- peri-areolar IRX-2 (IRX-2 arm: 1 ml SQ x2 daily for 10 days + cyclophosphamide 300 mg/m2 IV x 1) preceding initiation of pembrolizumab + NAC... A subset of TNBCs experience brisk IO response following single-cycle IO (IOpath response), which is associated with 100% pCR in this preliminary dataset, highlighting IOpath as a potential surrogate biomarker to guide NAC de-escalation or omission in early-stage TNBC. Baseline 27-gene IO score predicts pCR and week 3 IOpath response. A future study is planned (neoINBRX) to evaluate the feasibility of combining baseline IO score with week 3 IOpath response to identify and treat IO-sensitive tumors with chemotherapy-sparing IO combination therapy.

P1b, N=8, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2023 --> Dec 2023 | Trial primary completion date: Jun 2023 --> Dec 2023

P2, N=105, Completed, Brooklyn ImmunoTherapeutics, LLC | Unknown status --> Completed

P1b/2; Active, not recruiting --> Completed | N=20 --> 9

Survival analysis in 28 advanced lung cancer patients treated with an anti-PD-1 regimen at Nanfang hospital revealed that the LATPS-low subgroup had better immunotherapy benefit. LATPS is an effective predictor to distinguish survival, immune characteristics, and immunotherapy benefit in LUAD patients.

P1b/2; Suspended --> Active, not recruiting | Trial completion date: Feb 2022 --> Feb 2023 | Trial primary completion date: Feb 2022 --> Feb 2023

P1, N=16, Active, not recruiting, Providence Health & Services | Trial completion date: Dec 2020 --> Jan 2023 | Trial primary completion date: Apr 2018 --> Oct 2022

Background: In stage II/III TNBC, pembrolizumab when combined with chemotherapy (doxorubicin, cyclophosphamide, paclitaxel [ACT], and carboplatin) improves event free survival and pathologic complete response (pCR) rate (Keynote-522 study)...2 Page, DB. Clin Cancer Res 2020; 26.7:1595-1605.

Background Background: The FDA has approved pembrolizumab in combination with neoadjuvant chemotherapy (doxorubicin, cyclophosphamide, paclitaxel [ACT], and carboplatin) for stage II/III TNBC, on the basis of improved event free survival (EFS) and pathologic complete response (pCR) rate in the Keynote-522 study.1 Novel combination immunotherapy strategies may further improve outcomes and allow the opportunity to de-escalate the chemotherapy backbone, potentially mitigating grade III/IV toxicities which occurred in 81% of recipients...As of 7/28/2021, n=7/30 subjects are enrolled (Providence Cancer Institute, Portland, OR, Providence St. John’s Cancer Institute, Santa Monica, CA, Baylor Medicine, Houston, TX).

P1b/2, N=20, Suspended, City of Hope Medical Center | Trial completion date: Feb 2021 --> Feb 2022 | Recruiting --> Suspended | Trial primary completion date: Feb 2021 --> Feb 2022

Exploratory mIF biomarker outcomes in clinical trials may depend on the method of image analysis. Further work is ongoing to evaluate and improve upon discordant results using QuPath v. InForm. These data also highlight the importance of collaborative efforts via the NIH Cancer Immune Monitoring and Analysis Centers to standardize and validate mIF methodologies across institutions.

P1; mIF is useful for quantifying treatment-related dynamic changes in sTILs/PD-L1 and is concordant with clinical assays, but with greater precision. Hierarchical linear modeling can mitigate the effects of intratumoral heterogeneity on immune cell count estimations, allowing for more efficient detection of treatment-related pharmocodynamic effects in the context of clinical trials.

P1b/2, N=20, Recruiting, City of Hope Medical Center | Suspended --> Recruiting

The findings demonstrate significant increases in TILs after perilymphatic IRX-2 injections. Three quarters of patients showed significant immune responses to IRX-2. (NCT02609386).

EMP1 is upregulated in OS tissues and closely linked to lymphatic metastasis and distant metastasis. It stimulates the malignant progression of OS through the IRX2/MMP9 axis.

P1b/2, N=20, Suspended, City of Hope Medical Center | Recruiting --> Suspended

Potential of our newly genes as novel biomarkers of CML progression, particularly, blast crisis transformation should be tested. Furthermore, further functional cellular and molecular biological studies should be carried out to explore their role as novel drug targets for advanced phase CML.

mIF is concordant with SP142 and sTIL prognostic assays, but with increased precision to quantify treatment related changes. Regression modeling can dramatically improve the utility of mIF as a surrogate immune-based biomarker. Our approach is being utilized in ongoing phase II studies to compare the activity of pembrolizumab +/- locoregional cytokines (IRX-2) in triple negative BC, and paclitaxel/trastuzumab +/- pembrolizumab +/- pertuzumab in HER2-positive BC.

IRX-2 is safe in early stage breast cancer. Potentially favorable immunomodulatory changes were observed, supporting further study of IRX-2 in early stage breast cancer and other malignancies.

Introduction: Anti-PD-1/L1 (atezolizumab) is effective in first-line, PD-L1-positive triple negative breast cancer, however it is becoming increasingly apparent that the majority of breast cancers will require novel I-O combination strategies... We describe a framework for use of mIF as a high-dimensional biomarker for use with I-O clinical trials to gain mechanistic insight into the biologic effects of I-O therapies in primary BCs. mIF can be used to detect dynamic changes in sTIL score and IC PD-L1 expression, and therefore may serve to complement the H&E sTIL score and SP142 PD-L1 clinical assay in the context of I-O clinical trials. The greater precision of regression-assisted mIF may facilitate discovery of treatment-related I-O effects, potentially with smaller sample size requirements.