Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

BC-819 60, 120 and 240 mg IP administration

Cohort #1: 60 mg IP weekly for 3 weeks, one week rest, then repeat for 2 more courses / 60 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

Cohort #2: 120 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

Cohort #3: 240 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

BC-819

Tally Levy, M.D.

David Edelman, MD

Ami Fishman, MD

Eitan Rami, MD.

Ofer Lavie, M.D.

Ronnie Shapira-Frommer, MD

This study is designed to assess the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of DTA-H19 administered intraperitoneally (IP) in subjects with advanced stage ovarian cancer, or primary peritoneal carcinoma

This is a Phase 1/2a, open label, dose escalation, repeat dose study in 11 subjects with recurrent, platinum resistant advanced stage ovarian cancer or primary peritoneal carcinoma designed to determine the tolerability, safety, quality of life, PK, and preliminary efficacy of DTA-H19 administered intraperitoneally(IP).

Primary Objective: The primary objectives of this study are:

* To determine the maximum tolerated dose (MTD) of IP DTA-H19; and,
* To identify any dose limiting toxicities (DLTs).

Secondary Objectives: Secondary objectives of this study are:

* To determine quality of life of subjects with advanced ovarian cancer, primary peritoneal carcinoma treated with IP DTA-H19;
* To determine the the reduction in malignant ascites as measured by Ultrasound and change in frequency of parecenteses necessary.
* To determine the overall survival distribution.

Phase 1/2a Study of DTA-H19 in Advanced Stage Ovarian Cancer

Phase 1/2a, Dose-Escalation, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Intraperitoneal Administration of DTA-H19 in Subjects With Advanced Stage Ovarian Cancer

A dose limiting toxicity (DLT) was defined as any grade 3 or greater non-hematologic AE by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). If one subject in a cohort experienced a DLT, then three additional subjects had to be enrolled to that cohort unless a second subject in that cohort experiences a DLT. The next lower dose was to be considered the MTD.

Overall survival, defined as the time from the start of treatment until the subject died, was estimated by Kaplan Meier curves.

If measurable disease was present, then the response of each marker lesion was evaluated separately and rated for response according to RECIST criteria for solid tumors.

Complete Response: Disappearance of the target lesion. Partial Response: At least a 30% decrease in the longest diameter of the target lesion.

Stable Disease: No sufficient shrinkage to qualify for partial response, or sufficient increase to qualify for progressive disease.

Progressive Disease: At least a 20% increase in the longest diameter of the target lesion.

Blood was collected at the indicated time points, then analyzed with a quantitative polymerase chain reaction (Q-PCR) method to quantitate the amount of plasmid present.

Anchiano Therapeutics Israel Ltd.

60 mg IP weekly for 3 weeks, one week rest, then repeat for 2 more courses / 60 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

BC-819 60 mg IP

120 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

BC-819 120 mg IP

BC-819 240 mg IP

BC-819 60 mp IP

240 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Israel

Region of Enrollment

VP Clinical

Per Protocol data set (PP): 11 subjects who met the study inclusion and exclusion criteria, received at least one course of treatment of the investigational product and had a follow-up disease assessment comprised the PP set (5 subjects from the 60 mg cohort, 3 subjects from the 120 mg cohort; 3 subjects from the 240 mg cohort).

Number of Participants With Dose-Limiting Toxicities

Intent to Treat (ITT) data set: subjects who participated in the study were included in the safety and in the ITT analysis. All 14 subjects who participated in the study were included in the ITT.

Overall Survival in ITT Population

Stable Disease

Progressive Disease

Not evaluable

Intent To Treat (ITT) data set: subjects who participated in the study were included in the safety and in the ITT analysis. All 14 subjects who participated in the study were included in the ITT. 13 patients of the ITT population (n=14) were evaluated (one patient was not assessed for solid tumor response in the BC-819 60 mg IP Arm).

Solid Tumor Response

Intent To Treat (ITT) data set: subjects who participated in the study were included in the safety and in the ITT analysis. All 14 subjects who participated in the study were included in the ITT.

Systemic BC-819 Pharmacokinetics (PK) by Treatment - T1/2 (Hours)

60 mg IP weekly for 3 weeks, one week rest, then repeat for 2 more courses/ 60 mg IP weekly for 3 weeks, four week rest, then repeat for 1 more course.

Systemic BC-819 Pharmacokinetics (PK) - Maximum Observed Plasma Concentration (Cmax)

Systemic BC-819 Pharmacokinetics (PK) by Treatment - Tmax (Hours)

Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUClast

Systemic BC-819 Pharmacokinetics (PK) by Treatment - AUCinf

Overall Survival in PP

Overall Study

Digestive System Diseases

Infections

Pancreatic Neoplasms

Diphtheria

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

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.

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

United States

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

Maximal Tolerated Dose (MTD) & Dose Limiting Toxicity (DLT) of Intratumoral Injections of BC-819

Urinary Bladder Neoplasms

Non-Muscle Invasive Bladder Neoplasms

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

BCG Vaccine

BC-819 at 20 mg/50 mL, instilled intravesically into the bladder, with a retention time of at least 30 minutes (up to 2 hours).

Induction Phase (weekly treatments): 10 weekly treatments; Maintenance Phase: treatment every 3 weeks for up to 84 additional weeks

inodiftagene vixteplasmid

This study, BC-819-18-204, is a Phase 2, open-label, monotherapy, single-arm, multicenter clinical trial of BC-819 (inodiftagene vixteplasmid) in patients with NMIBC adequately treated with Bacillus Calmette-Guerin (BCG) whose disease is BCG unresponsive according to the US Food and Drug Administration (FDA) guidance.

BC-819 (inodiftagene vixteplasmid) is a recombinant DNA plasmid that directs the expression of a potent toxin specifically in malignant cells but not in normal tissue. It has been designed to exploit the established biology of the H19 gene, which is upregulated and expressed at high levels only in malignant cells, to produce bacterial diphtheria toxin only in bladder cancer tissue. BC-819 is administered directly into the bladder to enable maximal topical exposure to target bladder cancer cells.

Codex: Study of Inodiftagene Vixteplasmid (BC-819) in Unresponsive NMIBC

A Phase 2 Study of BC-819 in Patients With Non-Muscle Invasive Bladder Cancer Whose Disease is Unresponsive to Bacillus Calmette-Guerin

Complete response is defined as at least one of the following:

* Negative cystoscopy and negative (including atypical) urine cytology
* Positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative cytology
* Negative cystoscopy with malignant urine cytology if cancer is found in the upper tract or prostatic urethra and random bladder biopsies are negative

The complete response in patients with CIS for this endpoint was documented on or after the Week 12 response assessment and on or prior to the Week 48 assessment. Duration of complete response in patients with CIS was calculated from the documented onset of the complete response to the assessment where the patient no longer met the definition of complete response.

Time to recurrence (Kaplan-Meier plot) recurrence is defined as the reappearance or persistence of high-grade disease, or new high-grade disease. Recurrence must be biopsy proven. Persistence, appearance, or presence of lower grade disease was not considered to be a recurrence event

Time to recurrence (Kaplan-Meier plot) recurrence is defined as the reappearance or persistence of high-grade disease, or new high-grade disease. Recurrence must be biopsy proven. Persistence, appearance, or presence of lower grade disease was not considered to be a recurrence event.

The incidence of PFS at 48, 72, and 96 weeks as well as time to progression estimated using Kaplan-Meir methods. Progression is defined as the development of T2 or greater disease. Sensitivity analyses was performed and included any of the following as progressions:

* An increase in stage from Ta or CIS to T1, or
* Development of T2 or greater, or
* Lymph node disease, or
* Distant metastasis

Overall survival of patients enrolled in the study at 48, 72, and 96 weeks and survival time was estimated using Kaplan-Meier methods

Measured by the The European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30), a general questionnaire for assessing quality of life in cancer patients, and the Non-Muscle Invasive Bladder Cancer Questionnaire (QLQ-NMIBC24 ) for patients with NBIMC disease. EORTC QLQ-C30 include five functional scales , three symptom scales, a global health status/quality of life scale, and six single items. QLQ-NMIBC24 include five multi-item symptom scales, one multi-item functional scale, and five single-item measures.These scales range in score 0-100 scale and an for functional scales, a higher a higher score corresponds to greater function or quality of life. For symptom scales, a higher score corresponds to greater symptom burden.

The safety was evaluated by assessment of AEs according to CTCAE version 5.0, regardless of relationship to study medication.

The administration of BC-819 was separated into 2 phases, the induction phase, and the maintenance phase. During the induction phase, patients were to receive an intravesical instillation of BC-819 at a dose of 20 mg/50 mL aqueous solution once per week for 10 weeks according to the induction phase treatment schedule. Upon completion of the induction phase, patients transitioned to maintenance therapy of BC-819 every 3 weeks beginning at Week 12 (Visit 11) and continuing for the next 84 additional weeks until the end of the study, defined as completion of the 96-week visit (Visit 39).

Single Arm BC-819

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Weight

Height

Eastern Cooperative Oncology Group (ECOG) performance status is used by healthcare professionals to assess the progression of disease in cancer patients and is a standard criteria to determine how the disease impacts patient's daily living abilities.

GRADE ECOG PERFORMANCE STATUS

0 Fully active

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light nature.
2. Ambulatory and capable of all selfcare but unable to carry out any work activities
3. Capable of only limited selfcare
4. Completely disabled
5. Dead

Baseline ECOG performance status

David Kerstein, M.D.,Chief Medical Officer

17 participants had efficacy assessment for this Outcome Measure.

The Percentage of Patients With Baseline CIS That Achieve a Complete Response After Treatment With BC-819 (Measured at 12 Weeks)

Percentage of Patients With Absence of High-grade Recurrent or Persistent Disease at 48 Weeks (Overall Population and Subgroup of Patients With CIS)

Percentage of Patients With Absence of High-grade Recurrent or Persistent Disease at 12, 24, 36, 72, and 96 Weeks (Overall Population and Subgroup of Patients With CIS)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1/2a Study of DTA-H19 in Advanced Stage Ovarian Cancer	NCT00826150	Ovarian Cancer	BC-819	18 Years -	Anchiano Therapeutics Israel Ltd.
Phase 1/2a Study of DTA-H19 in Advanced Stage Ovarian Cancer	NCT00826150	Ovarian Cancer	BC-819	18 Years -	Anchiano Therapeutics Israel Ltd.
Phase 1/2a DTA-H19 in Patients With Unresectable Pancreatic Cancer	NCT00711997	Pancreatic Neop...	DTA-H19	18 Years - 79 Years	Anchiano Therapeutics Israel Ltd.
Codex: Study of Inodiftagene Vixteplasmid (BC-819) in Unresponsive NMIBC	NCT03719300	Non-muscle Inva...	inodiftagene vi...	18 Years -	Anchiano Therapeutics Israel Ltd.

Spots Global Cancer Trial Database for inodiftagene vixteplasmid