Study of Talimogene Laherparepvec (T-VEC) in Pancreatic Cancer

NCT03086642 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: AAAQ99661R01FD006108-01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out which doses of talimogene laherparepvec (T-Vec) can be given safely to participants with pancreatic cancer that is either too big to be taken out by surgery or has spread to other parts of the body. The study will also see if T-Vec can cause tumor shrinkage or prevent its growth. The primary objective is to determine the rate of dose limiting toxicity at tested doses of talimogene laherparepvec administered endoscopically to pancreatic tumors, and to identify a maximum tolerated dose (MTD). Secondary exploratory efficacy endpoints include change in longest diameter in the injected lesion(s), overall response rate (ORR) per RECIST v1.1 and modified immune-related response criteria (mirRC as defined in section 11), progression free survival (PFS) and overall survival (OS) at 6, 12, and 24 months. Funding Source - FDA OOPD

Conditions

Pancreatic Cancer

Keywords

locally advanced pancreatic cancer; locally advanced pancreas cancer; metastatic pancreatic cancer; metastatic pancreas cancer; refractory; refractory pancreatic cancer; refractory pancreas cancer; T-Vec; T Vec

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  To determine the highest dose of study treatment that does not cause unacceptable side effects.

  36-48 months

Secondary Outcomes (4)

• Change in size of injected lesion(s)

  baseline, 11 weeks

• Overall response rate (ORR)

  Up to 24 months

• Progression-free survival (PFS)

  Up to 24 months

• Overall survival (OS)

  Up to 24 months

Study Arms (1)

T-Vec

EXPERIMENTAL

All enrolled patients will receive a test dose of talimogene laherparepvec (10\^6 plaque forming units (PFU)/ml) on day 1, followed by treatment doses at escalating concentrations weeks 4, 7, and 10. A biopsy will be obtained during each scheduled endoscopy prior to talimogene laherparepvec injection.

Drug: Talimogene laherparepvec

Interventions

Talimogene laherparepvec DRUG

T-Vec will be administered by intratumoral injection into pancreatic tumors accessible endoscopically with ultrasound guidance (at least one pancreatic lesion must be injected during each treatment). On day 1 of week 1 the first dose of talimogene laherparepvec will be up to 4.0 mL of 10\^6 PFU/mL. The second injection up to 4.0 mL of 10\^6, 10\^7, or 10\^8 PFU/mL should be administered no sooner than day 1 of week 4 but should not be delayed more than 7 days after the scheduled time point. The maximum volume of T-Vec administered at any one time is 4.0 mL for any individual lesion.

Also known as: T-Vec, T Vec

T-Vec

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have pathologically confirmed, locally advanced or metastatic pancreatic adenocarcinoma deemed surgically unresectable by a surgeon with expertise in pancreatic cancer
• Disease must be refractory to or intolerant of at least first-line chemotherapy which contains 5-fluorouracil or gemcitabine
• The primary lesion must be accessible for endoscopic biopsy and injection as evaluated by a gastroenterologist at NewYork Presbyterian -Columbia. Further, the patient must be deemed able to tolerate repeated endoscopy procedures by an anesthesiologist and/or gastroenterologist at NewYork Presbyterian-Columbia
• Age 18 years or older
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• Radiologically measurable injectable disease in the pancreas or surgical bed from prior ≥1cm, as defined by RECIST v1.1
• Ability to understand and the willingness to sign a written informed consent document
• Females of child-bearing potential (defined as a sexually mature woman who (1) has not undergone hysterectomy \[the surgical removal of the uterus\] or bilateral oophorectomy \[the surgical removal of both ovaries\] or (2) has not been naturally postmenopausal for at least 24 consecutive months \[i.e., has had menses at any time during the preceding 24 consecutive months\]) must:
• i. Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis), or agree to use, and be able to comply with, effective contraception (\</=1% failure rate annually) without interruption, 28 days prior to starting therapy (including dose interruptions), and while on study medication or for a period of 30 days following treatment completion. \[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\].
• ii. Have a negative urine or serum pregnancy test within 72 hours prior to enrollment. If urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.This applies even if the subject practices true abstinence from heterosexual contact.
• Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 30 days following treatment discontinuation, even if he has undergone a successful vasectomy.
• Adequate organ and marrow function as defined below without need for hematopoietic growth factor or transfusion support:
• Hemoglobin ≥8.0g/dl
• Platelets ≥75,000/microliter (mcL)
• Absolute neutrophil count (ANC) ≥1500/mm3 (1.5x109/L)

You may not qualify if:

• Cystic pancreatic cancer. Microcystic disease may be eligible
• Patients with pancreatic metastases deemed likely to limit the patient's ability to participate in the study for the complete duration (ie. \>3 months), including but not limited to:
• a. Presence of central nervous system (CNS) metastasis including brain metastasis or compromise resulting from extrinsic disease in the bone or dura b. Presence of more than 5 liver metastases or one liver metastasis measuring more than 3cm c. Oxygen requirement attributable to pleural effusion or other malignant process d. Symptomatic ascites or radiographic evidence of more than trace ascites
• History of other malignancy within the past 3 years with the following exceptions:
• malignancy treated with curative intent and with no known active disease present and has not received chemotherapy for \>3 years before randomization and felt to be at low risk for recurrence by the treating physician
• adequately treated non-melanoma skin cancer without evidence of disease at the time of randomization • adequately treated cervical carcinoma in situ without evidence of disease at the time of randomization
• adequately treated breast ductal carcinoma in situ without evidence of disease at the time of randomization • prostatic intraepithelial neoplasia without evidence of prostate cancer at the time of randomization
• adequately treated superficial or in situ carcinoma of the bladder without evidence of disease at the time of randomization
• Pancreatitis that is active or within the preceding 3 months which in the judgment of the endoscopist would make tumor injection likely to trigger severe recurrent pancreatitis.
• Prior chemotherapy or radiotherapy within 14 days prior to first dose of therapy or has not recovered to CTCAE grade 1 or better from adverse event at time of enrollment due to cancer therapy administered more than 28 days prior to enrollment. or prior biological cancer therapy, targeted therapy, or major surgery within 28 days prior to first dose of therapy or unresolved grade 2 or greater toxicity from prior treatment, including chemotherapy, hormonal therapy, or radiotherapy, at the time of study enrollment. The following ongoing treatments are permitted:
• Hormone-replacement therapy or oral contraceptives
• Hormone therapy for primary prevention of breast cancer
• \. Patients may not receive Coumadin while on study. Patients may receive low molecular weight heparin or novel oral anticoagulants (eg. dabigatran, apixaban, rivaroxaban) provided that the dose is held 1-2 days before injections are given and biopsies are performed per the protocol. Anti-platelet agents and herbal substances are allowed at the discretion of the treating endoscopist.
• \. Radiation to the abdominal area within 28 days of first dose of therapy or prior radiotherapy in which the field does not overlap the injection sites or non-immunosuppressive targeted therapy within 14 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 14 days prior to enrollment. .
• \. The patient has not recovered to CTCAE grade 1 or better from adverse event at time of enrollment due to cancer therapy administered more than 28 days prior to enrollment

Sponsors & Collaborators

• Karie D. Runcie, MD: lead
• Amgen: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (1)

• Runcie K, Bracero Y, Samouha A, Manji G, Remotti HE, Gonda TA, Saenger Y. Phase I study of intratumoral injection of talimogene laherparepvec for the treatment of advanced pancreatic cancer. Oncologist. 2025 Jan 17;30(1):oyae200. doi: 10.1093/oncolo/oyae200.

  PMID: 39673447 DERIVED

Related Links

• Cancer Center's clinical trials online search tool

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

talimogene laherparepvec

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Karie Runcie, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: March 16, 2017
• First Posted: March 22, 2017
• Study Start: November 16, 2017
• Primary Completion: May 13, 2021
• Study Completion: December 31, 2022
• Last Updated: November 22, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)