Clostridium novyi-NT / BioMed Valley Discoveries - LARVOL DELTA

Biomed Valley Discoveries Announces Publication of Results from Phase 1b Study of Pembrolizumab in Combination with Clostridium novyi-NT (CNV-NT/BVD-550) in Patients with Advanced Solid Tumors in Clinical Cancer Research (GlobeNewswire) - "The confirmed ORR of 25% was observed among four patients with various tumor types, including nonkeratinizing undifferentiated nasopharyngeal squamous carcinoma, human papilloma virus–positive squamous cell carcinoma of the base of the tongue, vulvar melanoma, and chordoma (a rare cancer that originates in the bones of the spine or the skull). Among these patient responders, three partial responses and one complete response were observed, with a median duration of response of 10.93 months. Stable disease was observed in 69% of patients."

P1 data • Chordoma • Nasopharyngeal Carcinoma • Squamous Cell Carcinoma • Tongue Carcinoma • Vulvar Cancer

Phase Ib Study of Pembrolizumab in Combination with Intratumoral Injection of Clostridium novyi-NT in Patients with Advanced Solid Tumors. (PubMed, Clin Cancer Res) - "This study highlights the potential of the C. novyi-NT and pembrolizumab combination as a promising therapeutic strategy for treatment-refractory solid tumors."

Journal • P1 data • Breast Cancer • Chordoma • Dermatology • Hematological Disorders • Leukopenia • Melanoma • Oncology • Pruritus • Solid Tumor • Squamous Cell Carcinoma • Vulvar Cancer

Phase Ib Study of Pembrolizumab in Combination with Intratumoral Injection of Clostridium novyi-NT in Patients with Advanced Solid Tumors (Clin Cancer Res) - P1 | N=18 | NCT03435952 | "The combination therapy demonstrated a manageable safety profile, with one grade 3 dose-limiting toxicity (DLT) of abscess formation and the remainder of treatment-related adverse events (TRAEs) in ≥ 10% of patients being grade 1 or 2 injection site reaction (25%), pyrexia (19%), pruritus (13%), leukopenia (13%) and anemia (13%). The maximum tolerated dose (MTD) was determined as pembrolizumab IV 200mg every 3 weeks and a single dose of 100x104 C.novyi-NT spores IT on Day8. The confirmed overall objective response rate of 25%(n=4) was observed among patients with undifferentiated nasopharyngeal squamous carcinoma, squamous cell carcinoma of the base of the tongue, vulvar melanoma, and chordoma. Among these patients we obtained 3 partial responses and one complete response. Median duration of response was 10.93 months, and stable disease was observed in 69% patients."

P1 data • Chordoma • Melanoma • Nasopharyngeal Carcinoma • Squamous Cell Carcinoma • Tongue Carcinoma • Vulvar Cancer

Pembrolizumab with Intratumoral Injection of Clostridium Novyi-NT (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Oct 2024 ➔ Oct 2026 | Trial primary completion date: Oct 2024 ➔ Oct 2026

Combination therapy • Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Endocrine Cancer • Eye Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Oral Cancer • Solid Tumor • Thyroid Gland Carcinoma • PD-L1

Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Brain Cancer • Breast Cancer • CNS Tumor • Endocrine Cancer • Eye Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Oral Cancer • Solid Tumor • Thyroid Gland Carcinoma • PD-L1

Phase Ib Study of Pembrolizumab in Combination with Intratumoral Injection of Clostridium novyi-NT in Patients with Advanced Solid Tumors (AACR 2023) - P1 | "Intratumoral C. novyi-NT with pembrolizumab demonstrates clinical activity with favorable tolerability in patients regardless of tumor histology. This study is ongoing to define the recommended phase 2 dose (NCT03435952)."

Clinical • Combination therapy • Metastases • P1 data • Chordoma • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Vulvar Cancer

[VIRTUAL] First-in-man clinical trial of intratumoral injection of Clostridium novyi-NT spores in combination with pembrolizumab in patients with treatment-refractory advanced solid tumors (SITC 2020) - P1 | "Conclusions Single intratumoral injection of C. novyi-NT in combination with pembrolizumab has been demonstrating manageable toxicity profile and encouraging signals of anticancer activity. The enrolment continues."

Clinical • Combination therapy • Anal Carcinoma • Appendix Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Tongue Carcinoma

Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Oct 2021 ➔ Oct 2024 | Trial primary completion date: Oct 2021 ➔ Oct 2024

Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Endocrine Cancer • Eye Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Oral Cancer • Solid Tumor • Thyroid Gland Carcinoma • Urothelial Cancer • PD-L1

Paired 18F-Fluorodeoxyglucose (18F-FDG), and 64Cu-Copper(II)-diacetyl-bis(N(4)-methylthiosemicarbazone) (64Cu-ATSM) PET Scans in Dogs with Spontaneous Tumors and Evaluation for Hypoxia-Directed Therapy. (PubMed, Radiat Res) - "Clostridium novyi-NT (CNV-NT) is an oncolytic bacterium derived from attenuated wild-type Clostridium novyi spores, which germinates exclusively in the anaerobic core of tumors with low-oxygen content...64Cu-ATSM PET scanning predicts hypoxia patterns within spontaneously occurring tumors of dogs as measured by direct oxymetry. Total tumor volume does not accurately predict degree or proportion of tumor hypoxia."

Journal • Brain Cancer • Immunology • Melanoma • Oncology • Sarcoma • Solid Tumor • FDG PET

[VIRTUAL] First-in-man clinical trial of intratumoral injection of Clostridium novyi-NT spores in combination with pembrolizumab in patients with treatment-refractory advanced solid tumors (SITC 2020) - P1 | "Conclusions Single intratumoral injection of C. novyi-NT in combination with pembrolizumab has been demonstrating manageable toxicity profile and encouraging signals of anticancer activity. The enrolment continues."

Clinical • Combination therapy • Anal Carcinoma • Appendix Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Tongue Carcinoma

Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: M.D. Anderson Cancer Center; Trial primary completion date: Oct 2020 ➔ Oct 2021

Clinical • Combination therapy • Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Endocrine Cancer • Eye Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Oral Cancer • Solid Tumor • Thyroid Gland Carcinoma • Urothelial Cancer • PD-L1

Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT (clinicaltrials.gov) - P1; N=18; Not yet recruiting; Sponsor: M.D. Anderson Cancer Center

Clinical • Combination therapy • New P1 trial • Brain Cancer • Breast Cancer • CNS Tumor • Endocrine Cancer • Eye Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Oral Cancer • Solid Tumor • Thyroid Gland Carcinoma • Urothelial Cancer • PD-L1

Pembrolizumab With Intratumoral Injection of Clostridium Novyi-NT (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: M.D. Anderson Cancer Center; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Brain Cancer • Breast Cancer • CNS Tumor • Endocrine Cancer • Eye Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oral Cancer • Thyroid Gland Carcinoma • Urothelial Cancer • PD-L1