Study of Talimogene Laherparepvec In Children With Advanced Non CNS Tumors

NCT02756845 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 201102612015-003645-25
• Study Type: interventional
• Target: 15
• Locations: 7 countries
• Sites: 22

Brief Summary

This is a phase 1 study to evaluate the safety of intralesional talimogene laherparepvec administration in pediatric subjects with advanced non-CNS tumors that are amenable to direct injection

Conditions

Advanced Non CNS Tumors

Keywords

Non CNS Tumor

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Experienced a Dose-limiting Toxicity (DLT)

  All toxicities were graded using the Common Terminology Criteria for Adverse Events version 4.0: * Grade 1: Mild * Grade 2: Moderate * Grade 3: Severe/medically significant but not immediately life-threatening * Grade 4: Life-threatening * Grade 5: Death related to adverse event The occurrence of any of the below was considered a DLT, if judged to be related to talimogene laherparepvec: * Grade 4 non-hematologic toxicity * Grade 3 non-hematologic toxicity that lasted \> 3 days despite optimal supportive care * Any ≥ grade 3 non-hematologic laboratory value if medical intervention was required, the abnormality led to hospitalization or the abnormality persisted for \> 1 week unless deemed not clinically important per both investigator \& sponsor * Febrile neutropenia grade 3/4 * Thrombocytopenia \< 25 x 10\^9/L associated with bleeding event that required intervention * Serious herpetic event * Grade 5 toxicity * Any intolerable toxicity that led to permanent discontinuation of talimogene laherparepvec

  Day 1 to Day 35

Secondary Outcomes (6)

• Overall Response Rate (ORR)

  Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months

• Duration of Response (DOR)

  Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months

• Time to Response (TTR)

  Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months

• Time to Progression (TTP)

  Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months

• Progression Free Survival (PFS)

  Every 12 weeks until the end of follow-up; maximum duration of follow-up was 54.51 months

Study Arms (1)

Talimogene Laherparepvec (TVEC)

EXPERIMENTAL

The first dose of talimogene laherparepvec will be administered at a dose of up to 4.0 mL of 10ᶺ6 PFU/mL followed by a dose of up to 4.0 mL of 10ᶺ8 PFU/mL 21 days (+3 days) later. Subsequent doses of up to 4.0 mL of 10ᶺ8 PFU/mL will be administered every 14 days (± 3 days) thereafter. Cohorts will be assigned as follows: Cohort A1 (age 12 to ≤ 21 years). Cohort B1 (age 2 to \< 12 years). The DLRT will review the safety data of the first 3 subjects in the older age cohort A1 to decide if the younger age cohort B1 can be opened for enrollment. If dose de-escalation is needed and if permissible based on the incidence of DLTs, additional DLT-evaluable subjects will be enrolled and treated at a lower dose level of talimogene laherparepvec. Dose de-escalation cohorts will be assigned as follows and the same DLT rules will be applied: Cohort A2 (age 12 to ≤ 21 years), Cohort B2 (age 2 to \< 12 years).

Drug: Talimogene Laherparepvec

Interventions

Talimogene Laherparepvec DRUG

Talimogene laherparepvec will be administered by intralesional injection only into injectable cutaneous, subcutaneous, nodal tumors, and other non-visceral tumors with or without image ultrasound guidance. The first dose of talimogene laherparepvec will be up to 4.0 mL of 10\^6 PFU/mL administered on day 1. The second injection, up to 4.0 mL of 10\^8 PFU/mL (or up to 4.0 mL of 10\^6 PFU/mL for a dose de-escalated cohort), will be administered 21 (+3) days after the initial injection. All subsequent injections, up to 4.0 mL of 10\^8 PFU/mL (or up to 4.0 mL of 10\^6 PFU/mL for a dose de-escalated cohort), will be administered every 14 (± 3) days. The treatment cycle interval may be increased due to toxicity.

Also known as: TVEC

Talimogene Laherparepvec (TVEC)

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subject's legally acceptable representative has provided informed consent/assent when the subject is legally too young to provide informed consent/assent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated.
• Should be willing to submit local HSV-1 serostatus within 28 days prior to enrollment.
• Subject must be a candidate for intralesional injection, defined as one or more of the following:
• at least 1 injectable lesion ≥ 10 mm in longest diameter
• multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm
• Life expectancy \> 4 months from the date of enrollment.
• Male or female subjects 2 to ≤ 21 years of age at the time of informed consent/assent.
• Histologically or cytologically confirmed non-CNS solid tumor that recurred after standard/frontline therapy, or for which there is no standard/frontline therapy available.
• Presence of measurable or non-measurable lesions as defined by irRC-RECIST
• Performance status as per protocol
• Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to dosing.
• Adequate organ function as defined in protocol

You may not qualify if:

• Diagnosis of leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, or other hematologic malignancy.
• Radiotherapy to the bone marrow within 6 weeks prior to enrollment OR within 3 months prior to enrollment if prior radiotherapy to the craniospinal axis or to at least 60% of the pelvis was received; within 2 weeks prior to enrollment if local palliative radiotherapy was received.
• Primary ocular or mucosal melanoma.
• History of other malignancy within the past 5 years with the following exception:
• malignancy treated with curative intent and with no known active disease present and has not received chemotherapy for \> 5 years before enrolment and felt to be at low risk for recurrence by the treating physician.
• History or evidence of active autoimmune disease that requires systemic treatment (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Active herpetic skin lesions or prior complications of herpetic infection (eg, herpetic keratitis or encephalitis).
• Prior treatment with talimogene laherparepvec or any other oncolytic virus.
• Prior treatment with a tumor vaccine.
• Requires intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.
• Expected to require other cancer therapy while on study with the exception of local palliative radiation treatment.
• Has acute or chronic active hepatitis B virus or hepatitis C virus infection or received treatment with nucleotide analogs such as those used in the treatment of hepatitis B virus (eg, lamivudine, adefovir, tenofovir, telbivudine, and entecavir), ribavirin, or interferon alpha within 12 weeks of initiation of study treatment.
• Known or suspected human immunodeficiency virus (HIV) infection.
• Received live vaccine within 28 days prior to enrollment.
• No antiplatelet or anticoagulation medications allowed within 7 days prior totalimogene laherparepvec injection except low-dose heparin needed to maintain venous catheter patency.

Sponsors & Collaborators

• Amgen: lead

Study Sites (22)

AI Dupont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Nemours du Pont Hospital in Florida

Jacksonville, Florida, 32207, United States

Location

Ann and Robert H Lurie Childrens Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Childrens Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Childrens Hospital

Columbus, Ohio, 43205, United States

Location

Childrens Hospital of Philidelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Centre Hospitalier Universitaire Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Institut Hematologie et Oncologie Pediatrique

Lyon, 69373, France

Location

Centre Hospitalier Universitaire de Marseille - Hopital de la Timone

Marseille, 13385, France

Location

Institut Curie

Paris, 75005, France

Location

IRCCS Ospedale Pediatrico Bambino

Roma, 00165, Italy

Location

Hospital Universitario Virgen del Rocio

Seville, Andalusia, 41013, Spain

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital Sant Joan de Deu

Esplugues de Llobregat, Catalonia, 08950, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, Valencia, 46026, Spain

Location

Hospital Universitario Infantil Niño Jesus

Madrid, 28009, Spain

Location

Universitaets-Kinderspital beider Basel

Basel, 4031, Switzerland

Location

Universitaets-Kinderspital

Zurich, 8032, Switzerland

Location

Related Publications (1)

• Moreno L, Teira P, Croop JM, Gerber NU, Andre N, Aerts I, Gros Subias L, De Wilde B, Bautista F, Turpin B, Kunduri S, Hamidi A, Lawrence T, Streby KA. A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors. Front Pediatr. 2023 May 24;11:1183295. doi: 10.3389/fped.2023.1183295. eCollection 2023.

  PMID: 37292376 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

talimogene laherparepvec

Limitations and Caveats

Participant recruitment ended when 15 participants were enrolled due to difficulties in enrollment.

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Approximately 18 to 24 treated pediatric subjects are expected to be enrolled into 2 cohorts stratified by age (permissible based on the incidence of DLTs, a minimum of 6 subjects/cohort and a minimum of 18 subjects total). * Cohort A1 (12 to ≤ 21 years of age) * Cohort B1 (2 to \< 12 years of age) Initially, 3 subjects 12 to ≤ 21 years of age are to be enrolled and treated at 100% of the recommended adult dose regimen of talimogene laherparepvec (cohort A1). The dose level review team (DLRT) will review the safety data of the first 3 subjects in the older age cohort A1 to decide if the younger age cohort B1 can be opened for enrollment. If a DLT occurs in the first 3 DLT-evaluable subjects in the older age cohort (A1 or A2), the younger age cohort will not open until a DLT rate \< 33% is observed with at least 6 DLT-evaluable subjects in the older age cohort (A1 or A2).

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: April 29, 2016
• Study Start: August 16, 2017
• Primary Completion: January 17, 2022
• Study Completion: November 29, 2022
• Last Updated: February 20, 2024
• Results First Posted: February 5, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

BE (1); FR (3); CH (2); ES (5); US (9); IT (1); CA (1)