T3011 in Combination With Cobimetinib in Patients With Advanced Melanoma

NCT05756556 | Suspended Phase 2 FDA Drug

• 1 other identifier: MVR-T3011-IT-2004
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the efficacy and safety of T3011 in combination with Cobimetinib in patients with advanced melanoma.

Conditions

Melanoma; Malignant Melanoma

Keywords

intratumoral (IT) injection; Cobimetinib; advanced melanoma; RAS mutation-positive; BRAF V600E/V600K mutation-positive; stage IIIB to IV advanced malignant melanoma

Outcome Measures

Primary Outcomes (2)

• ORR

  defined as the proportion of patients with a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST version 1.1

  up to 5 years after the first dose of the last patient, depending on the actual situation.

• Characterize the safety and tolerability of T3011 in combination with Cobimetinib.

  Incidence and severity of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs) (part 1 only), adverse event of special interest (AESIs), abnormal clinically significant vital signs, physical examination, and laboratory tests, with severity determined according to national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0.

  up to 5 years after the first dose of the last patient, depending on the actual situation.

Secondary Outcomes (5)

• Overall Survival (OS)

  up to 5 years after the first dose of the last patient, depending on the actual situation.

• Progression-free survival (PFS)

  up to 5 years after the first dose of the last patient, depending on the actual situation.

• Disease control rate (DCR)

  up to 5 years after the first dose of the last patient, depending on the actual situation.

• Duration of response (DOR)

  up to 5 years after the first dose of the last patient, depending on the actual situation.

• European Organization for Research and Treatment of Cancer Questionnaire Core 30 (EORTC QLQ-C30)

  up to 5 years after the first dose of the last patient, depending on the actual situation.

Study Arms (1)

Phase 2a

EXPERIMENTAL

T3011 given via intratumoral (IT) injection in combination with Cobimetinib via oral administration in patients with advanced melanoma.

Combination Product: T3011 + Cobimetinib

Interventions

T3011 + Cobimetinib COMBINATION_PRODUCT

1e8 plaque-forming units (PFU)/mL (up to 10 mL, every 2 weeks \[Q2W\], 28 days/cycle) T3011 will be administered in combination with 60 mg Cobimetinib (once daily \[QD\] for the first 21 days of each 28-day cycle)

Phase 2a

Eligibility Criteria

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

You may qualify if:

• Patient has provided informed consent prior to initiation of any study-specific activities/procedures.
• Male or female age ≥ 18 years at the time of informed consent.
• Willingness to provide pre-and post-treatment fresh tumor biopsy specimens as specified in the Schedule of Study Procedures and Assessments (Table 1).
• Histologically confirmed diagnosis of malignant melanoma (except for uveal melanoma).
• Patient with stage IIIB to IV advanced malignant melanoma (as defined by American Joint Committee on Cancer \[AJCC\] staging manual version 8.0) that is not surgically resectable, failed for standard of care (SOC) therapy or in the opinion of the investigator not suitable for SOC therapy. SOC may include, but not be limited to chemotherapy, targeted therapy or immunotherapy.
• BRAF V600E/V600K mutation-positive (applied to part 1 and part 2 cohort 1) or RAS mutation-positive (applied to part 1 and part 2 cohort 2). BRAF V600E/V600K and RAS mutation status result from diagnosis of tumor histopathology should be provided during Screening. If the patient is unable to provide, testing will be required during the Screening period in local laboratory.
• Measurable disease defined as one or both of the following:
• （1） At least 1 melanoma lesion that can be accurately and serially measured in at least 2 dimensions sand for which the longest diameter is ≥ 10 mm and with perpendicular diameter ≥ 5 mm as measured by contrast-enhanced or spiral CT scan for visceral or nodal/soft tissue disease. Lymph nodes must measure \> 15 mm in their short axis to be considered measurable by CT scan.
• （2） At least 1 superficial cutaneous or subcutaneous melanoma lesion that can be accurately and serially measured in at least 2 dimensions and for which the short axis is ≥ 5 mm as measured by calipers.
• （3） Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that lesion since radiation.
• \. Injectable disease (i.e., suitable for direct injection or through the use of ultrasound \[US\] or CT guidance) defined as follows:
• At least 1 injectable melanoma lesion ≥ 5 mm in longest diameter, or in the opinion of the investigator the lesion can be injected.
• \. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• \. Life expectancy ≥ 12 weeks.
• \. Adequate bone marrow function defined by ANC of ≥ 1.5 × 109/L, platelet count of ≥ 100 × 109/L, and hemoglobin (Hb) of ≥ 8.5 g/dL.

You may not qualify if:

• Patients are to be excluded from the study if they meet any of the following criteria:
• Prior treatment with other Oncolytic virus (OV) (including but not be limited to T-VEC), tumor vaccines, cellular therapy or gene therapy.
• Prior local anti-tumor therapy \< 21 days prior to the first dose of study treatment; prior systemic targeted therapy (including but not be limited to MEK inhibitors) \< 21 days or last dose of therapy with MEK inhibitors \< 5 times the half-life prior to first dose of study treatment; prior other anti-tumor therapy (including but not be limited to PD-1/programmed cell death ligand 1\[PD-L1\]) \< 21 days prior to the first dose of study treatment, prior major surgery \< 21 days prior to the first dose of study treatment.
• Prior treatment with anti-PD-(L)1 monoclonal Ab in combination with IL-12.
• Previous intolerance to anti-PD-(L)1 monoclonal Ab or previous history of immunotherapy induced ≥ NCI CTCAE version 5.0 Grade 3 non-infectious pneumonitis/interstitial lung disease.
• The following foods/supplements are used within 7 days before the study treatment or the following foods/supplements are planned to be used during the study treatment:
• （1） St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer).
• （2） Grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor).
• \. Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection that would interfere with absorption of study drugs, inability or unwillingness to swallow the formulated product.
• \. A history of metastasis to the brain stem, midbrain, pons/medulla oblongata, or within 10 mm of optic nerve organs (optic nerve and optic chiasma); Or a history of leptomeningeal metastasis.
• \. Patients with rapidly disease progression, defined as patients who cannot tolerate interruption of systemic anti-tumor therapy for at least 8 weeks, according to the investigator's judgment.
• \. Primary or acquired immunodeficient status (leukemia, lymphoma, human immunodeficiency virus \[HIV\]/acquired immunodeficiency syndrome \[AIDS\]).
• \. History or evidence of active autoimmune disease that requires systemic treatment (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) within 4 weeks prior to first dose of study treatment. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• \. History or evidence of active primary immunodeficiency. 12. Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection).

Sponsors & Collaborators

• ImmVira Pharma Co. Ltd: lead

Study Sites (1)

Gabrail Cancer and Research Center

Canton, Ohio, 44718, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

cobimetinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a phase 2a, open-label study of T3011 given via intratumoral (IT) injection in combination with Cobimetinib given via oral administration in patients with advanced melanoma. This study is planned to enroll approximately 62\~68 patients with BRAF V600E/V600K mutation-positive or RAS mutation-positive, which will be conducted in 2 parts (part 1 and part 2)

Study Record Dates

• First Submitted: December 23, 2022
• First Posted: March 6, 2023
• Study Start: June 30, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: February 1, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)