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Diphtheria

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Pancreatic Cancer

Cohort #1: 4 mg DTA-H19 intratumorally 2 times per week for 2 weeks Cohort #2: 8 mg DTA-H19 intratumorally 2 times per week for 2 weeks

DTA-H19

Abraham Czerniak, MD

Nader Hanna, MD, FACS

Fred Konikoff, MD

Ayala Hubert, MD

This study is designed to assess the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of DTA-H19 administered intratumorally in patients with unresectable, locally advanced pancreatic cancer.

Primary Objective: The primary objective is to determine the maximum tolerated dose (MTD) of intratumoral DTA-H19 and identify any dose limiting toxicities (DLTs).

Secondary objectives include determining the adverse events (AEs) profile, effects on clinical laboratory analytes, vital signs, PK, tumor response, and possible tumor resectability after 4 intratumoral administrations of DTA-H19.

DTA-H19, is a doubled stranded DNA plasmid that carries the gene for the diphtheria toxn A (DT-A) chain under the regulation of the H19 promoter sequence. This is a Patient-Oriented, Targeted Therapy as DT-A chain expression is triggered by the presence of H19 transcription factors that are upregulated in tumor cells. The selective initiation of toxin expression results in selective tumor cell destruction via inhibition of protein synthesis in the tumor cell, enabling highly targeted cancer treatment.

Phase 1/2a DTA-H19 in Patients With Unresectable Pancreatic Cancer

Phase 1/2a, Dose-Escalation, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Intratumoral Administration of DTA-H19 in Patients With Unresectable Pancreatic Cancer

If 2 patients in any cohort experience DLTs, then the next lower dose will be considered the MTD if there is a lower dose cohort. A DLT is defined as grade 3 or greater toxicity judged to be at least possibly related to the investigational products.

Tumor response and progression were defined in accordance with RECIST v. 1.0 and assessed by radiological examination 2 weeks after the end of treatment

The number of subjects in each cohort whose tumor was resectable at the end of the study was to be presented for the ITT and the per-protocol population.

Anchiano Therapeutics Israel Ltd.

1 mL of 4 mg/mL for a total of 4 mg of BC-819 per injection for 2 weeks of twice weekly intratumoral BC-819.

BC-819 4 mg

2 mL of 4 mg/mL for a total of 8 mg of BC-819 per injection for 2 weeks of twice weekly intratumoral BC-819.

BC-819 8 mg

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Israel

Region of Enrollment

Monique Ben-Am, M.Sc.

Stable disease

Progressive disease

Each cohort of 3 to 6 subjects received 2 weeks of twice weekly intratumoral injections of BC-819. Intratumoral injections were performed using PTA- or EUS-guided administrations of BC-819. For each treatment, this cohort received a single injection of 1 mL of 4 mg/mL for a total of 4 mg of BC-819 per injection.

Each cohort of 3 to 6 subjects received 2 weeks of twice weekly intratumoral injections of BC-819. Intratumoral injections were performed using PTA- or EUS-guided administrations of BC-819. For each treatment, this cohort received a single injection of 2 mL of 4 mg/mL for a total of 8 mg of BC-819.

Tumor Response

Tumor Resectability

1 mL of 4 mg/mL for a total of 4 mg of BC-819 per injection for 2 weeks of twice weekly intratumoral BC-819. Intratumoral injections were performed using CT-guided PTA or EUS of BC-819.

2 mL of 4 mg/mL for a total of 4 mg of BC-819 per injection for 2 weeks of twice weekly intratumoral BC-819. Intratumoral injections were performed using CT-guided PTA or EUS of BC-819.

All participants had to receive all 4 scheduled treatments and completed the Week 4 assessment

Spots Global Cancer Trial Database for h19 gene, plasmid, diphtheria toxin, pancreatic cancer