Combination Therapy With GEN0101 and Pembrolizmub in Advanced Melanoma Patients PIb/PII

NCT03818893 | Unknown Phase 2 DMC

• 1 other identifier: GEN0101-JM005
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 7

Brief Summary

This is a multi-center, open-labeled, non-randomized, single arm investigator-initiated trial to evaluate the safety and efficacy of GEN0101 and Pembrolizmub combination in patients with advanced melanoma.

Conditions

Advanced Melanoma

Keywords

Cancer immunotherapy

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR), central review

  As overall tumor response in all the tumors in each subject, the ORR is calculated based on the assessment results in Week 9 (Day 57th), Week 13 (Day 85th) and Week 17 (Day 113th) as confirmatory assessment.

  until Week17 (Day113th)

Secondary Outcomes (6)

• Overall response rate (ORR) and Best overall response (BOR), investigator assessment and central review

  until Week 105 (Day 729th)

• Percent change in individual tumor sizes

  Until Week 105 (Day 729th)

• Progression free survival (PFS)

  Until Week 105 (Day 729th)

• Overall survival (OS)

  Until Week 105 (Day 729th)

• Induction of antitumor immunity

  Week 13 (Day 85th)

Study Arms (1)

New Combination Immunotherapy

EXPERIMENTAL

Patients will receive Pembrolizumab once every 3 weeks and a maximum of 35 doses over 105 weeks . The patients should be inpatient during treatment with GEN0101 in each treatment cycle and may be outpatient during off-treatment period with GEN0101, observation period, follow-up period with Pembrolizumab. GEN0101 in a vial will be reconstituted with 1 mL of sterile distilled water and then will be injected intracutaneously (including skin tumor site). Nonetheless, it will not be deemed as deviation if an injection has been given subcutaneously unintentionally, e.g., leakage around the peri-injection sites. A dose will be 60,000 mNAU in total, and 1 mL per injection site should be administered to 6 injection sites in total. For a patient, the total dose in a treatment cycle will be 360,000 mNAU (360 NAU), and the total dose over 2 treatment cycles will be 720,000 mNAU (720 NAU).

Drug: Combination of GEN0101 and Pembrolizmub

Interventions

Combination of GEN0101 and Pembrolizmub DRUG

New Combination immunotherapy GEN0101 and Pembrolizmub

New Combination Immunotherapy

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient will be eligible for this trial if all the following apply:
• Patient has given written informed consent by themselves
• Patient aged 20 to 85 years at the time of informed consent
• Patient has histologically- or cytologically-confirmed melanoma
• Patient with a diagnosis of incurable and unresectable, Stage IIIC, IIID or Stage IV advanced melanoma, showing confirmed SD or unconfirmed PD over 12-week treatment with an anti-PD-1 antibody such as nivolumab or Pembrolizumab. To be assigned a status of SD, changes in tumor measurements must be confirmed by consecutive repeat evaluations that should be performed in 4 to 6 weeks after the criteria for response are first met over 12-week of an anti-PD-1 antibody treatment.
• Patient has a measurable tumor
• Patient has life expectancy of at least 12 weeks after the first dose of investigational product
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening
• Patient has met the following criteria of clinical laboratory tests at screening (1)White blood cell (WBC) count over 3,000/μL and neutrophil count over 1,500/μL (2)Platelet count over over 75,000/μL (3)Hemoglobin over 8.0 g/dL (4)AST and ALT ≤ 2.5 × upper limit of normal (ULN) (5)Total bilirubin ≤ 2 × ULN (6)Serum creatinine ≤ 2 × ULN
• LDH is not higher than the 2-fold of the upper limit of the institutional reference.
• A female patient of childbearing potential (a premenopausal woman, a woman with medically or drug-induced amenorrhea, and a woman with no history of sterilization), who has agreed to use appropriate contraception, e.g., the barrier method and a total abstinence, during the trial treatment until 3 months passed after completion of the trial treatment. A male patient who has agreed to use appropriate contraception, e.g., the barrier method and a total abstinence, during the above period.

You may not qualify if:

• Patient will be excluded from participation if any of the following apply:
• Patient has brain metastases. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging\* (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Patient has showed positive reaction in a prick testing for GEN0101
• A patient who has the mutant BRAF gene in a tumor biopsy.
• A patient who has current pneumonitis.
• Patient concurrently has an active infection requiring systemic therapy.
• Patient has received other systemic anticancer therapy than an anti-PD-1 antibody therapy such as nivolumab, Pembrolizumab, or local IFN-beta therapy within 3 weeks before the time of informed consent (or within 6 weeks before the time of the informed consent for a patient who received nitrosourea or mitomycin C)
• Patient has received another unapproved drug other than anti-PD-L1 antibody within 4 weeks before the time of informed consent
• Patient has intraocular (uveal) melanoma
• Patient has or had another malignant tumor than melanoma. However, this criterion does not apply to a patient who has experienced neither recurrence nor metastasis for at least 5 years at the time of informed consent.
• Patient has received systemic corticosteroid or systemic immunosuppressant within 1 week before the first dose of investigational product. However, this criterion does not apply to a patient who has been on long-term (\>6-month) treatment at a low dose (equivalent to oral prednisolone under 10 mg/day) or who received prophylactic immunosuppressant against contrast media allergy.
• Patient has received a live vaccine within 30 days before registration
• Patient has enrolled in another clinical trial and received an investigational product within 4 months before the first dose of investigational product, or patient has intended to be enrolled in another clinical trial in parallel with this clinical trial
• A patient who has an active TB infection.
• Female patient is pregnant (including one with positive results from a pregnancy test at screening), lactating, or intending to become pregnant during participation in this trial and before 3 months have passed after completion of this trial. However, this criterion does not apply to a patient who will stop lactating (from the date of informed consent until 30 days passed after the last treatment). Of note, female patients should undergo a beta-HCG test to demonstrate pregnancy status. Male patient who does not agree to use appropriate contraception such as the barrier method and a total abstinence during this trial until 3 months passed after the completion of this trial. (Detailed method is described in 5.7 Contraception)

Sponsors & Collaborators

• Osaka University: lead
• Merck Sharp & Dohme LLC: collaborator
• ISHIHARA SANGYO KAISHA,LTD. Japan: collaborator

Study Sites (7)

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8550, Japan

NOT YET RECRUITING

Sapporo Medical University Hospital

Sapporo, Hokkaido, 060-8543, Japan

NOT YET RECRUITING

Kumamoto University Hospital

Kuramoto, Kumamoto, 860-8556, Japan

RECRUITING

Shizuoka Cancer Center

Nakatogari, Shizuoka, 411-8777, Japan

NOT YET RECRUITING

Tokyo Medical and Dental University

Bunkyo-ku, Tokyo, 113-8519, Japan

NOT YET RECRUITING

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

RECRUITING

Osaka International Cancer Institute

Osaka, 541-8567, Japan

NOT YET RECRUITING

Study Officials

• Atsushi Tanemura, Lecture

  Osaka University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Atsushi Tanemura, Lecture

CONTACT

06-6879-3039; tanemura@derma.med.osaka-u.ac.jp

Yukio Tanaka, Researcher

CONTACT

06-6210-8295; yukiotanaka@dmi.med.osaka-u.ac.jp

Study Design

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

Study Record Dates

• First Submitted: January 24, 2019
• First Posted: January 28, 2019
• Study Start: March 1, 2019
• Primary Completion: December 31, 2021
• Study Completion: June 30, 2022
• Last Updated: January 30, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

JP (7)