Study to Evaluate the Safety/ Efficacy of T-VEC in Japanese Subjects With Unresectable Stage IIIB-IV Malignant Melanoma

NCT03064763 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 20140270
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 9

Brief Summary

There are 2 fold of purposes for this study. 1 is to evaluate safety and tolerability and the other is to study the anti-tumor effects of talimogene laherparepvec in Japanese participants with unresectable stage IIIB-IV malignant melanoma.

Conditions

Unresectable Stage IIIB-IV Malignant Melanoma

Keywords

Unresectable Stage IIIB-IV Malignant Melanoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced One or More Dose Limiting Toxicities (DLTs)

  DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4 Events were considered DLTs, if judged by the investigator to be related to study treatment: Grade 4 non-hematologic toxicity Grade 3 non-hematologic toxicity lasting \> 3 days despite optimal supportive care (grade 3 fatigue not a DLT) Grade 3 or higher non-hematologic laboratory value reported as an adverse event if: medical intervention is required, or abnormality leads to hospitalization, or abnormality persists for \> 1 week (Laboratory values that persist for \> 1 week but are deemed not clinically important per both investigator and sponsor were not considered DLTs) Febrile neutropenia grade 3 or 4 Thrombocytopenia \< 25 x 10\^9/L associated with bleeding event requiring intervention Serious herpetic event (eg, herpetic encephalitis, encephalomyelitis, or disseminated herpetic infection) Grade 5 toxicity Any other intolerable toxicity leading to permanent discontinuation of study treatment

  Day 1 to Day 35

• Durable Response Rate (DRR) Using Modified World Health Organization (WHO) Response Criteria

  DRR using WHO response criteria was defined as the percentage of participants who experienced objective response (complete response \[CR\] or partial response \[PR\]) lasting continuously for ≥ 6 months that starting any time within 12 months of initiating treatment. CR: Complete disappearance of all index lesions, including any new tumors which might have appeared. PR: Achieving a 50% or greater reduction in the SPD of the perpendicular diameters of all index lesions at the time of assessment as compared to the sum of the products of the perpendicular diameters of all index lesions at baseline (Day 1).

  Day 1 up to the maximum time on treatment or follow-up at primary data cutoff date (03 August 2020): 89.1 weeks of treatment and 37 months of follow-up

Secondary Outcomes (5)

• Overall Response Rate (ORR) Using Modified World Health Organization (WHO) Response Criteria

  Day 1 to end of study, maximum time to end of study was 212.6 weeks

• Time to Response (TTR) Using Modified World Health Organization (WHO) Response Criteria

  Day 1 to end of study, maximum time to end of study was 212.6 weeks

• Duration of Response (DOR) Using Using Modified World Health Organization (WHO) Response Criteria

  Day 1 to end of study, maximum time to end of study was 212.6 weeks

• Progression Free Survival (PFS) Using Using Modified World Health Organization (WHO) Response Criteria

  Day 1 to end of study, maximum time to end of study was 212.6 weeks

• Overall Survival (OS)

  Day 1 to end of study, maximum time to end of study was 212.6 weeks

Study Arms (1)

Talimogene laherparepvec

EXPERIMENTAL

Participants will receive talimogene laherparepvec administered by intralesional injection only into injectable cutaneous, subcutaneous, and nodal tumors, with or without image ultrasound guidance. On Day 1 (Week 0), the initial dose of talimogene laherparepvec will be up to 4.0 mL of 10\^6 Plaque forming units per millilitre (PFU/mL). Subsequent doses of talimogene laherparepvec will be up to 4.0 mL of 10\^8 or 10\^7 PFU/mL. The second dose is to be administered 3 weeks (+ 5 days) after the initial dose, and subsequent doses were to be given every 2 weeks (+ 3 days).

Drug: Talimogene laherparepvec

Interventions

Talimogene laherparepvec DRUG

Talimogene laherparepvec will be administered as an intralesional injection.

Also known as: Imlygic, T-VEC

Talimogene laherparepvec

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of melanoma
• Participants with stage IIIB to IVM1c melanoma that is not surgically resectable
• Participant who is treatment naive and is determined by the physician to be not suitable or eligible for the approved systemic anticancer drug therapy in Japan. Participant may also have received prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy. Treatment for melanoma must have been completed at least 28 days prior to enrollment.
• Candidate for intralesional therapy (ie, disease is appropriate for direct injection or through the use of ultrasound guidance, where appropriate) defined as one or more of the following:
• at least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion greater or equal to 10 mm in longest diameter, OR
• multiple injectable melanoma lesions that in aggregate have a longest diameter of greater or equal to 10 mm
• Measurable disease defined as one or more of the following:
• at least 1 melanoma lesion that can be accurately and serially measured in at least 2 dimensions and for which the greatest diameter is greater or equal to 10 mm as measured by contrast-enhanced or spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or ultrasound for nodal/soft tissue disease (including lymph nodes)
• at least 1 greater or equal to 10 mm longest diameter superficial cutaneous or subcutaneous melanoma lesion as measured by calipers
• multiple superficial melanoma lesions which in aggregate have a total diameter of greater or equal to 10 mm
• Serum lactate dehydrogenase (LDH) levels less than or equal to 1.5 X upper limit of normal (ULN) within 28 days prior to enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

You may not qualify if:

• Clinically active cerebral metastases. Participants with up to 3 cerebral metastases may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy (including Gamma Knife) or craniotomy, with no evidence of progression and have not required steroids for at least 2 months prior to enrollment.
• Greater than 3 visceral metastases (this does not include lung metastases or nodal metastases associated with visceral organs). For participants with less than or equal to 3 visceral metastases, no lesion greater than 3 cm in longest dimension and liver lesions must be stable for at least 1 month prior to enrollment.
• Bone metastases
• Primary ocular or mucosal melanoma
• History or evidence of symptomatic autoimmune disease (eg, pneumonitis, glomerulonephritis, vasculitis, or other), or history of autoimmune disease that required systemic treatment (ie, use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past 2 months prior to enrollment.
• Active herpetic skin lesions or prior complications of herpetic infection (eg, herpetic keratitis or encephalitis).
• Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.
• Previous treatment with talimogene laherparepvec
• Other investigational procedures while participating in this study are excluded.
• Known to have acute or chronic active hepatitis B infection, acute or chronic active hepatitis C infection or human immunodeficiency virus (HIV) infection
• Participant has known sensitivity to bovine- or porcine derived components or to any of the products or components to be administered during dosing.
• History of other malignancy within the past 3 years

Sponsors & Collaborators

• Amgen: lead

Study Sites (9)

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Sapporo Medical University Hospital

Sapporo, Hokkaido, 060-8543, Japan

Location

Kumamoto University Hospital

Kumamoto, Kumamoto, 860-8556, Japan

Location

Shinshu University Hospital

Matsumoto-shi, Nagano, 390-8621, Japan

Location

Niigata Cancer Center Hospital

Niigata, Niigata, 951-8566, Japan

Location

Osaka International Cancer Institute

Osaka, Osaka, 541-8567, Japan

Location

Shizuoka Cancer Center

Sunto-gun, Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Related Publications (1)

• Yamazaki N, Isei T, Kiyohara Y, Koga H, Kojima T, Takenouchi T, Yokota K, Namikawa K, Yi M, Keegan A, Fukushima S. A phase I study of the safety and efficacy of talimogene laherparepvec in Japanese patients with advanced melanoma. Cancer Sci. 2022 Aug;113(8):2798-2806. doi: 10.1111/cas.15450. Epub 2022 Jun 30.

  PMID: 35656636 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

talimogene laherparepvec

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: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2017
• First Posted: February 27, 2017
• Study Start: March 7, 2017
• Primary Completion: August 3, 2020
• Study Completion: January 12, 2023
• Last Updated: August 9, 2023
• Results First Posted: June 14, 2021

Record last verified: 2023-07

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

JP (9)