Talimogene Laherparepvec in Patients With Unresectable Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

The purpose of the study is to assess the safety of injections of talimogene laherparepvec into patients with pancreatic cancer that cannot be removed by surgery. The study will also test whether the injections are effective in treating the tumor.

Detailed description public domain (ClinicalTrials.gov)

Talimogene laherparepvec is a conditionally replication competent herpes simplex type-1 virus designed for use in solid tumors. It has been specifically modified to replicate in tumors and to provide a local source of the immune-stimulating cytokine, granulocyte macrophage colony stimulating factor (GM-CSF). It is injected directly into cancer tumors and is believed to destroy tumor cells by direct infection of the tumor cells and an enhanced immune response due to the release of tumor antigens and GM-CSF expression. This was an open-label, dose-escalation study evaluating the safety and efficacy of talimogene laherparepvec administered by direct injection into pancreatic tumors using endoscopic ultrasound (EUS)-guided fine needle injection (FNI). Only 1 tumor mass within the body and tail of the pancreas was injected in any participant. The protocol called for evaluation of 4 dosing regimens in sequential cohorts of participants; however, cohort 4 was not opened for enrollment.

Intervention public domain (ClinicalTrials.gov)

Biological: Talimogene Laherparepvec. Talimogene laherparepvec administered by direct injection into pancreatic tumors using EUS-guided FNI, up to a maximum of 4 mL per treatment.

Arm public domain (ClinicalTrials.gov)

Talimogene Laherparepvec (experimental): Participants received 3 doses of talimogene laherparepvec administered by direct injection 3 weeks apart. At the discretion of the investigator, treatment with talimogene laherparepvec could continue beyond the third dose until week 15 in a regimen of at least 3 weeks between doses.

Primary outcome public domain (ClinicalTrials.gov)

Number of Participants With Adverse Events. A serious adverse event is defined as any untoward medical occurrence that at any dose results in death, is life threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important and significant medical event that, based upon appropriate medical judgment, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed above. Time frame: From first dose of talimogene laherparepvec until 30 days after the last dose; the median duration of treatment was 44.0 days, 22.0 days, and 11.5 days in each group respectively..

Primary outcome public domain (ClinicalTrials.gov)

Number of Participants With Talimogene Laherparepvec Detected in Blood and Urine. Samples of blood and urine collected before and up to 24 hours after dosing were tested for the presence of talimogene laherparepvec deoxyribonucleic acid (DNA) using a validated quantitative polymerase chain reaction (qPCR) assay. Time frame: Treatment Day 1 predose and 2, 6, 12 and 24 hours postdose, and Week 3 and 6 at (predose and 2 hours postdose..

Primary outcome public domain (ClinicalTrials.gov)

Number of Participants Positive for Anti-herpes Simplex Virus-1 (HSV-1) Antibodies. Anti-HSV-1 antibodies were detected using an enzyme-linked immunosorbent assay (ELISA). Time frame: Week 0 (Day 1, predose) and Week 3.

Secondary outcome public domain (ClinicalTrials.gov)

Change From Baseline in Sum of Longest Diameters of Injected Tumors. Time frame: Baseline and Week 6, 12 and 18.

Secondary outcome public domain (ClinicalTrials.gov)

Number of Participants With Overall Objective Response. Time frame: Every 6 weeks until 12 weeks after the last dose; the median duration of treatment was 44.0 days, 22.0 days, and 11.5 days in each group respectively..

Secondary outcome public domain (ClinicalTrials.gov)

Change From Baseline in Pain Intensity. Time frame: Baseline and Weeks 3 and 6.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * cytological or histological proof of adenocarcinoma of the pancreas * unresectable, locally advanced disease (isolated liver metastases are permitted) * tumors of at least 1 cm diameter at screening * measurable disease using Response Evaluation Criteria In Solid Tumors (RECIST) criteria * failure of either standard therapy, OR any one of the following: * no alternative therapeutic of higher curative potential is available; * investigator determination that patient could not tolerate alternative therapeutic due to unacceptable toxicity; or, * patient refusal to be treated with available alternative therapeutic * age \> 18 years * life expectancy \> 3 months * adequate bone marrow function as indicated by: * White blood cells (WBC) ≥ 3.0 x 10\^9/L * platelets ≥ 100 x 10\^9/L * hemoglobin ≥ 8.5 gm/dL * adequate liver function as indicated by: * bilirubin \< 1.5 x upper limit of normal (ULN) * alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \< 5 x ULN in case of presence of liver metastasis * ALT or AST \< 2.5 x ULN in case of absence of liver metastasis * adequate renal function as indicated by a serum creatinine level \< 1.5 x ULN. * adequate hemostasis indicated by international normalized ratio (INR) ≤ 1.5 * mentally, physically and geographically able to undergo treatment and follow-up * provided written informed consent * first patient in each cohort only: seropositive for herpes simplex virus type 1 (HSV1) Exclusion Criteria: * history of other malignancy within two years prior to screening, except for prostate cancer (T1c, T2ab with definitive treatment, prostate-specific antigen (PSA) \< 1 ng/ml, and without ongoing hormone suppression) or adequately treated in situ carcinoma of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin * cystic form of pancreatic cancer; microcystic disease may be eligible upon discussion with Medical Monitor * Common Terminology Criteria for Adverse Events (CTCAE) version 3 grade 2 or greater clinical pancreatitis within 8 weeks prior to dosing with OncoVEX\^GM-CSF * other than metastases limited to the liver, imaging evidence of metastatic disease to any other organ or tissue * any serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator * evidence of compromised immune function including but not limited to: * clinically significant absolute lymphocyte count \< Lower Limit of Normal (LLN) * …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 17 participants (actual).

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Participants With Adverse Events [From first dose of talimogene laherparepvec until 30 days after the last dose; the median duration of treatment was 44.0 days, 22.0 days, and 11.5 days in each group respectively.]. Number, participants. Any adverse event: Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 3; Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 4; Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): 10. Serious adverse events: Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 2; Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 3; Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): 9. Deaths: Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 1; Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 1; Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): 6. Discontinued study treatment due to adverse event: Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 0; Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 0; Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): 2.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change From Baseline in Sum of Longest Diameters of Injected Tumors [Baseline and Week 6, 12 and 18]. Mean, mm (Standard Deviation). Week 6 (N=2, 1, 4): Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 2.5 (3.54); Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 18.0 (NA) [Could not be calculated due to a sample size = 1]; Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): -3.3 (12.42). Week 12 (N=1, 1, 0): Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 0.0 (NA) [Could not be calculated due to a sample size = 1]; Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 18.0 (NA) [Could not be calculated due to a sample size = 1]; Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): NA (NA) [Could not be calculated due to a sample size = 0]. Week 18 (N=2, 2, 1): Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 11.5 (9.19); Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 25.5 (10.61); Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): 37.0 (NA) [Could not be calculated due to a sample size = 1].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Number of Participants With Overall Objective Response [Every 6 weeks until 12 weeks after the last dose; the median duration of treatment was 44.0 days, 22.0 days, and 11.5 days in each group respectively.]. Number, participants. Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 0; Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 0; Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): 0.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Participants With Talimogene Laherparepvec Detected in Blood and Urine [Treatment Day 1 predose and 2, 6, 12 and 24 hours postdose, and Week 3 and 6 at (predose and 2 hours postdose.]. Number, participants. Blood: Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 0; Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 4; Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): 1. Urine: Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 1; Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 2; Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): 4.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Number of Participants Positive for Anti-herpes Simplex Virus-1 (HSV-1) Antibodies [Week 0 (Day 1, predose) and Week 3]. Number, participants. Baseline (predose) (N= 3, 3, 8): Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 2; Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 3; Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): 6. Week 3 (N=3, 3, 6): Talimogene Laherparepvec 10⁴/ 10⁵ PFU/mL (n=3): 3; Talimogene Laherparepvec 10⁵ / 10⁶ PFU/mL (n=4): 3; Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=10): 6.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change From Baseline in Pain Intensity [Baseline and Weeks 3 and 6]. Mean, cm (Standard Deviation). Week 3 (N=0, 0, 6): Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=6): 1.250 (2.456). Week 6 (N=0, 0, 4): Talimogene Laherparepvec 10⁶ / 10⁷ PFU/mL (n=6): 2.575 (3.305).