NanoDoce (docetaxel nanoformulation) / NanOlogy - LARVOL DELTA

Intratumoral Injection of Large Surface Area Microparticle Taxanes in Carcinomas Increases Immune Effector Cell Concentrations, Checkpoint Expression, and Synergy with Checkpoint Inhibitors: A Review of Preclinical and Clinical Studies. (PubMed, Oncol Ther) - "This review summarizes development of large surface area microparticle paclitaxel (LSAM-PTX) and docetaxel (LSAM-DTX) for local treatment of primary carcinomas with emphasis on immunomodulation...Synergistic benefits from combinatorial therapy in a 4T1-Luc breast cancer model included reduction of metastasis with IT LSAM-DTX + anti-mCTLA-4. IT LSAM-PTX and LSAM-DTX are tumoricidal, immune enhancing, and may improve solid tumor response to immune checkpoint inhibitors without additional systemic toxicity."

Checkpoint inhibition • IO biomarker • Journal • Preclinical • Review • Bladder Cancer • Breast Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Immunology • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor

NanOlogy Clinical and Preclinical Immune Data Presented at NACLC and SITC (Businesswire) - "NMIBC clinical subjects demonstrated infiltrations of CD4+T, CD8+ T, and NK cells. Mice administered IT LSAM-DTX into renal tumor xenografts had increased circulating T cells and reduced M2-macrophage levels in the blood and spleen when compared to IV docetaxel. IT LSAM-DTX in a metastatic breast cancer model increased T cells in the TME and reduced thoracic metastasis when combined with systemic immunotherapy."

Preclinical • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Safety of locally administered large surface area microparticle paclitaxel and docetaxel in combination with standard of care cancer therapies. (ASCO 2023) - P1, P1/2, P2, P2a | "Rates of subjects who had Grade 3 SAE possibly related to LSAM-PTX were 29%, 24%, 16%, 6.7% and 5.0% in paclitaxel, carboplatin, 5-FU, nab-paclitaxel, and gemcitabine combinations, respectively...No Grade 3-5 AE were reported with LSAM-DTX in combination with gemcitabine, carboplatin, pembrolizumab, avelumab or radiation... Local treatment of solid tumors with LSAM-PTX or LSAM-DTX has the potential to overcome some limitations of SOC therapies by increasing tumor dwell time and reducing systemic toxicities which are often exacerbated in combinatorial treatment regimens. Clinical trial information: NCT00666991, NCT03636256, NCT03077659, NCT04221828, NCT03029585, NCT03077685, NCT04314895. >X(Y) = Number of events (possibly related to LSAM)."

Clinical • Combination therapy • Bladder Cancer • Oncology • Solid Tumor

NanOlogy Presents Clinical Research at 2023 DDW and ASCO Involving its Large Surface Area Microparticle Investigational Drugs (Businesswire) - P2 | N=20 | NCT03188991 | Sponsor: NanOlogy, LLC | "NanOlogy LLC...announces a presentation of clinical research involving its large surface area microparticle (LSAM) investigational drugs at DDW 2023 in May and publication at ASCO Annual Meeting in June. 'In this protocol, intracystic LSAM-PTX was safe and resulted in cyst volume and surface area reduction, morphological changes, and loss of pathogenic mutations,'...'Further clinical research is warranted particularly in nonsurgical high-risk cyst patients because of the lack of approved treatments to decrease risk for progression to pancreatic cancer.' The ASCO abstract (e15187)...was accepted for publication in the ASCO annual meeting library....The review concluded that local treatment of solid tumors with LSAM-PTX or LSAM-DTX has the potential to overcome some limitations of SOC therapies by increasing tumor dwell time and reducing systemic toxicities which are often exacerbated in combinatorial treatment regimens."

P2 data • Retrospective data • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Urothelial Cancer

NanOlogy Publishes Review Article of Preclinical and Clinical Research Supporting LSAM-DTX (Businesswire) - P1/2 | N=36 | NCT03636256 | Sponsor: NanOlogy, LLC | "In the high risk nonmuscle invasive bladder cancer clinical trial arm (n=19) of a dose escalation/expansion trial of intramural and intravesical LSAM-DTX in urothelial carcinoma, 100%/78%/50% of subjects in the high-dose cohort (n=9) achieved a complete response at the 3/6/12 month timepoints respectively. Moreover, evidence suggesting favorable immunomodulation was reported after analysis of suitable tissue samples collected pre/post administration of LSAM-DTX....In addition to LSAM-DTX, NanOlogy clinical programs have advanced tumor-directed LSAM-PTX in pancreas, lung, peritoneal, ovarian, prostate, and dermal cancers."

Clinical • P1/2 data • Bladder Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Pancreatic Cancer • Peritoneal Cancer • Prostate Cancer • Skin Cancer • Solid Tumor • Urothelial Cancer

NanOlogy Publishes Review Article of Preclinical and Clinical Research Supporting LSAM-DTX (Businesswire) - "NanOlogy LLC...announced today that a review article of preclinical and clinical research supporting its investigational drug, large surface area microparticle docetaxel (LSAM-DTX), has been published in Drug Delivery and Translational Research (DDTR)....Highlights from the current article: LSAM-DTX is retained in the tumor as a depot for continuous drug release after intratumoral injection in a range of solid tumor preclinical models; LSAM‑DTX in combination with an immune checkpoint inhibitor demonstrated synergy in a preclinical metastatic breast cancer model; Evidence of efficacy is seen in preclinical xenograft models of bladder, prostate, and renal cancer as well as evidence of an abscopal effect in a preclinical syngeneic renal cell adenocarcinoma model."

Preclinical • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Kidney Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

Local administration of large surface area microparticle docetaxel to solid carcinomas induces direct cytotoxicity and immune-mediated tumoricidal effects: preclinical and clinical studies. (PubMed, Drug Deliv Transl Res) - "Encouraging clinical results indicate that local administration of LSAM-DTX may provide therapeutic benefits for non-muscle invasive bladder cancer and muscle invasive bladder cancer patients; treatments were well-tolerated with few local and systemic adverse events and negligible systemic docetaxel exposure. Results of preclinical and clinical investigations summarized here indicate that local administration of LSAM-DTX may augment tumor response to systemically administered chemotherapy, targeted therapy, or immunotherapy without contributing to systemic toxicity."

Journal • Preclinical • Review • Bladder Cancer • Breast Cancer • Genito-urinary Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Renal Cell Carcinoma • Solid Tumor • Urology • Urothelial Cancer

NanOlogy Publishes Results from a Phase 1/2 Clinical Trial of Large Surface Area Microparticle Docetaxel in High-Risk Non-Muscle Invasive Bladder Cancer (Businesswire) - P1/2 | N=36 | NCT03636256 | Sponsor: NanOlogy, LLC | "Direct-injection and intravesical LSAM-DTX were well-tolerated with minor recorded treatment-related local and systemic adverse events. Median recurrence free survival was 12.2 months in the high-dose and expansion cohorts and was significantly increased compared to the low dose cohorts at 5.4 months. Bladder biopsies show an increase in tumor microenvironment immunogenicity, including increases in adaptive (T cells) and innate (NK cells) effector cells....NanOlogy is planning further clinical development of LSAM-DTX, which it believes has therapeutic potential in NMIBC and muscle invasive bladder cancer, which also showed promising results in a separate arm of the trial and will be reported once finalized."

P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology

Phase 1/2 Trial Results of a Large Surface Area Microparticle Docetaxel for the Treatment of High-Risk Non-muscle Invasive Bladder Cancer. (PubMed, J Urol) - "Post-TURBT direct-injection and intravesical LSAM-DTX was well tolerated and demonstrated clinical response for patients with high-risk NMIBC. Favorable immune cell infiltration and checkpoint receptor increases following LSAM-DTX treatment warrants investigation alone as well as in combination with immune checkpoint inhibitor therapy."

Journal • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Urothelial Cancer • CTLA4 • PD-L1

Evaluation of NanoDoce® in Participants With Urothelial Carcinoma (clinicaltrials.gov) - P1/2; N=36; Completed; Sponsor: NanOlogy, LLC; Active, not recruiting ➔ Completed; N=75 ➔ 36; Trial primary completion date: Mar 2021 ➔ Nov 2021

Clinical • Enrollment change • Trial completion • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • Urology • Urothelial Cancer

AUA2021 Presentation Highlights Results from a Phase 1/2 Clinical Trial of Intramural/Intravesical NanoDoce Suspension in High-Risk Nonmuscle Invasive Bladder Cancer (Businesswire) - P1/2, N=75; NCT03636256; Sponsor: NanOlogy, LLC; "NanOlogy...announced today that initial results from a Phase 1/2 clinical trial of intramural/intravesical (IMI/IVT) NanoDoce® (large surface area microparticle [LSAM] docetaxel) suspension in high-risk nonmuscle invasive bladder cancer (hrNMIBC)...Across all doses and subjects (n=19), complete response (CR) at 3 months as 68% (13/19) and durability for responding subjects at 12 months was CR of 31% (4/13). In the high-dose cohort (n=6), 6/6 maintained CR > 6 months with 4 subjects showing durability at 12 months, 1 subject showing recurrence, and 1 subject lost to follow up."

P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Urothelial Cancer

[VIRTUAL] Initial Results from a Phase 1/2 Trial of Large Surface Area Microparticle Docetaxel for High-Risk Non-Muscle Invasive Bladder Cancer (AUA 2021) - P1/2 | "LSAM-DTX treatment was safe by both intramural injection and intravesical instillations. PK analysis demonstrated negligible systemic exposure. Preliminary efficacy data suggest post-TURBT intramural injection and intravesical instillation of high dose LSAM-DTX may prevent recurrence in patients with hrNMIBC for 6-months."

Late-breaking abstract • P1/2 data • Bladder Cancer • Genito-urinary Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

Submicron particle docetaxel intratumoral injection in combination with anti-mCTLA-4 into 4T1-Luc orthotopic implants reduces primary tumor and metastatic pulmonary lesions. (PubMed, Med Oncol) - "Myeloid-derived suppressor cells (MDSC) were reduced in bloods in SPD ± anti-mCTLA-4 groups (p < 0.05). These data demonstrate that both SPD and anti-mCTLA-4 produce local anti-tumor effects as well as reductions in metastasis which are significantly enhanced when administered in combination."

Combination therapy • Journal • Breast Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • Thoracic Cancer • CD4 • CD8

Evaluation of NanoDoce® in Participants With Urothelial Carcinoma (clinicaltrials.gov) - P1/2; N=75; Active, not recruiting; Sponsor: NanOlogy, LLC; Recruiting ➔ Active, not recruiting; Trial completion date: Nov 2020 ➔ Jan 2022; Trial primary completion date: Nov 2020 ➔ Mar 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urethral Cancer • Urology • Urothelial Cancer

NanOlogy Presents Results of SOR007 (Topical Submicron Particle Paclitaxel) Phase 1/2 Clinical Trial in the Treatment of Cutaneous Metastases at 2020 SABCS (Businesswire) - P1/2, N=23; NCT03101358; Sponsor: NanOlogy, LLC; “NanOlogy, LLC…announced that results from its Phase 1/2 clinical trial of SOR007 (topical submicron particle paclitaxel) in the treatment of cutaneous metastases were presented during the 2020 San Antonio Breast Cancer Symposium...The dose escalation/expansion trial enrolled 23 subjects across three clinical sites, 21 of whom had cutaneous metastases of breast cancer (CMOBC)…Best overall response in evaluable subjects for the 56-day treatment group (n=11) was 54% versus 27% for the 28-day treatment group (n=11). Preliminary signs in lesion pain reduction were observed in half of the subjects reporting lesion pain at baseline...In addition to SOR007, NanOlogy is advancing clinical programs aimed at solid tumor-directed therapy with investigational drugs NanoPac® (LSAM paclitaxel) for suspension and NanoDoce® (LSAM docetaxel) in pancreatic, peritoneal, ovarian, prostate, bladder, and lung cancers.”

P1/2 data • Trial status • Bladder Cancer • Breast Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Peritoneal Cancer • Prostate Cancer • Solid Tumor

Local administration of submicron particle paclitaxel to solid carcinomas induces direct cytotoxicity and immune-mediated tumoricidal effects without local or systemic toxicity: preclinical and clinical studies. (PubMed, Drug Deliv Transl Res) - "This report describes local administration of submicron particle paclitaxel (SPP) (NanoPac®: ~ 800-nm-sized particles with high relative surface area with each particle containing ~ 2 billion molecules of paclitaxel) in preclinical models and clinical trials evaluating treatment of carcinomas...Local administration of SPP may facilitate tumor response to systemically administered chemotherapy, targeted therapy, or immunotherapy without contributing to systemic toxicity. Results of preclinical and clinical investigations described here suggest that local administration of SPP achieves clinical benefit with negligible toxicity and may complement standard treatments for metastatic disease."

Journal • Review • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor

Trial of NanoDoce Intratumoral Injection in Renal Cell Carcinoma (clinicaltrials.gov) - P1; N=0; Withdrawn; Sponsor: NanOlogy, LLC; N=15 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Intratumoral submicron particle docetaxel inhibits syngeneic Renca renal cancer growth and increases CD4+, CD8+, and Treg levels in peripheral blood. (PubMed, Invest New Drugs) - "CD4+, CD8+ and Treg populations were increased in peripheral bloods from animals administered IT NanoDoce. Additional evaluation of the effect of IT NanoDoce on peripheral and local immune cell populations as well as the impact on sites of distant tumor growth are warranted."

Journal • CD8

Trial of NanoDoce Intratumoral Injection in Renal Cell Carcinoma (clinicaltrials.gov) - P1; N=15; Not yet recruiting; Sponsor: NanOlogy, LLC

Clinical • New P1 trial

Expanded Access to NanoDoce (clinicaltrials.gov) - P; N=N/A; Available; Sponsor: NanOlogy, LLC

New trial

"NanoDoce on trial" (@MaxKates)

Local Injection of Submicron Particle Docetaxel is Associated with Tumor Eradication, Reduced Systemic Toxicity and an Immunologic Response in Uro-Oncologic Xenografts. (PubMed, Cancers (Basel)) - "We hypothesize that local, persistent, therapeutic levels of docetaxel from IT-NanoDoce reduces tumor burden while increasing immune-cell infiltration. IT NanoDoce treatment of prostate, renal and bladder cancer may result in enhanced tumoricidal effects."

Journal

Evaluation of NanoDoce® in Participants With Urothelial Carcinoma (clinicaltrials.gov) - P1/2; N=75; Recruiting; Sponsor: NanOlogy, LLC; Not yet recruiting ➔ Recruiting; N=36 ➔ 75; Initiation date: Jan 2019 ➔ Apr 2019

Clinical • Enrollment change • Enrollment open • Trial initiation date

NanOlogy announces first patient enrolled in a phase 1/2 clinical trial of NanoDoc for treatment of bladder cancer (Businesswire) - "NanOlogy...announced the first patient has been enrolled in a clinical trial of NanoDoce (sterile submicron particle docetaxel suspension) for treatment of bladder cancer. The Phase 1/2 dose-rising trial will evaluate the safety and preliminary efficacy of NanoDoce for patients with high-risk non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC)."

Enrollment open

Newly added product (Businesswire) - P2, Bladder Cancer, Renal Cell Carcinoma, Urothelial Cancer

Pipeline update