GEN0101 and pembrolizumab combination therapy in patients with advanced melanoma

JRCT ID: jRCT2051190009

Registered date:22/04/2019

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: advanced melanoma
• Date of first enrollment: 06/03/2019
• Target sample size: 46
• Study type: Interventional
• Intervention(s): combination therapy of intracutaneous GEN0101 with intravenous Pembrolizumab

Outcome(s)

Primary Outcome

Overall response rate (ORR) , central review
-For each subject, the RECIST v1.1-based tumor response is assessed in Week 9 (Day 57th), Week 13 (Day 85th, unconfirmed) and Week 17 (Day113th, confirmed) of GEN0101. Antitumor effect is assessed centrally.
-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. Then, a one-sided test is performed with the significance level of 0.05 to examine significant difference to historical data of KEYNOTE-002 in the RRs in Week 13 (Day 85th before confirmation) and Week 17 (Day 113th after confirmation).

Secondary Outcome

Overall response rate (ORR) and Best overall response (BOR), investigator assessment and central review
In each subject, antitumor effect is assessed as described below until Week 105 (Day 729th) in comparison with the baseline, and then the antitumor effect of the combination therapy is investigated.
-In all the tumors in each subject, the RECIST v1.1-based overall tumor response is assessed by the site investigator until Week 105 (Day 729th). Then, based on the assessment results, the ORR and BOR are calculated.
-In all the tumors in each subject, the irRC-based overall tumor response is assessed centrally until Week 105 (Day 729th). Then, based on the assessment results, the ORR and BOR are calculated.
-In all the tumors in each subject, the irRECIST-based overall tumor response is assessed centrally until Week 105 (Day 729th). Then, based on the assessment results, the ORR and BOR are calculated.
(2)Percent change in individual tumor sizes
Until Week 105 (Day 729th) in each subject, the size of each tumor is calculated by the longest diameter the perpendicular diameter of each tumor, and then percent changes in individual tumor sizes (percent shrinkage or growth) and the local Response Rates are calculated.
(3)Progression free survival (PFS) and
When the last subject completed Week 22 (Day 148th) (and Week 26 as confirmatory assessment of PD) and Week 53 (Day 365th) and Week 105 (Day 729th) of GEN0101, the RECIST v1.1-based PFS is assessed for all the subjects, where the assessment results in Week 8 should not be used and the central assessment results since Week 13 (Day 85th) only are used for all the subjects.
(4)Overall survival (OS)
When the last subject completes Week 22 (Day 148th) and Week 53 (Day 365th) and Week 105 (Day 729th) of GEN0101, OS is calculated for all the subjects.
(5)Induction of antitumor immunity
In Week 9 (Day 57th) and Week 13 (Day 85th) of GEN0101 in each subject, the induction of antitumor immunity after the combination therapy is investigated with the index of peripheral blood activated NK cells.
(6)Safety
AEs occurring in each subject up to Week 105 (Day 729th) of GEN0101 are evaluated with CTCAE v4.03.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 86age old
• Gender: Both

Include criteria

Inclusion criteria
Patients meeting all of the criteria from 1) to 10) below are eligible for the trial.
1) A patient who gave written informed consent to trial enrollment of his or her own free will.
2) A patient who is aged 20 to 85 years.
3) A patient who was histologically or cytologically confirmed to have melanoma.
4) A patient with a diagnosis of incurable and unresectable, Stage 3C, 3D or Stage 4 advanced melanoma, showing confirmed SD or unconfirmed PD in assessment after 12 week treatment with anti PD1 antibody,
e.g., nivolumab or Pembrolizumab, and also in confirmatory assessment within successive 6 weeks.
5) A patient who has a measurable tumor.
6) A patient who is expected to survive for at least 12 weeks since the planned day of the first trial
treatment.
7) A patient whose ECOG performance status is 0 or 1.
8) A patient who has the following functions of the bone marrow, liver, and kidney at screening.
(1) White blood cells 3,000 micro L and also neutrophil count 1,500 micro L
(2) Platelet 75,000 micro L
(3) Hemoglobin 8.0 g per dL
(4) AST not higher than the 2.5 fold of the upper limit of the institutional reference
(5) ALT not higher than the 2.5 fold of the upper limit of the institutional reference
(6) Total bilirubin not higher than the 2 fold of the upper limit of the institutional reference
(7) Serum creatinine not higher than the 2 fold of the upper limit of the institutional reference
9) LDH is not higher than the 2 fold of the upper limit of the institutional reference.
10) 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.

Exclude criteria

Exclusion criteria
Patients meeting any of the criteria from 1) to 19) below are ineligible for the trial.
1)A patient who has brain metastases. However, 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.
To confirm the stability of the existing brain metastasis, when conducting image inspection of the brain, it should be carried out by MRI as much as possible. However, if MRI is contraindicated, contrast CT is allowed.
2)A patient who has showed positive reaction in a prick testing for GEN0101.
3)A patient who has the mutant BRAF gene in a tumor biopsy.
4) A patient who has current pneumonitis.
5) A patient who concurrently has an active infection requiring systemic therapy
6)A patient who has received other systemic anticancer therapy than anti PD1 antibody therapy, e.g., nivolumab or Pembrolizumab, or local IFN beta therapy within 3 weeks before informed consent (or within 6 weeks before informed consent for a patient received nitrosourea or mitomycin C).
7)A patient who has received another unapproved drug than the anti PD L1 antibody within 4 weeks before informed consent.
8)A patient who has intraocular (uveal) melanoma.
9)A patient who 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.
10)A patient who received a systemic corticosteroid or systemic immunosuppressant within 1 week before the first trial treatment. However, this criterion does not apply to a patient who has been on long term (in 6month) treatment at a low dose (equivalent to oral prednisolone 10 mg per day) or who received prophylactic immunosuppressant against contrast media allergy.
11)A patient who received a live vaccine within 30 days before registration.
12)A patient who was enrolled in another clinical trial and received an investigational drug within 4 months before the first trial treatment or a patient who intends to be enrolled in another clinical trial in parallel with this clinical trial.
13) A patient who has an active TB infection.
14)A female patient who is pregnant (including one with a positive result in the pregnancy test at screening), lactating, or intending to become pregnant during participation in the trial or before 3 months have passed after the completion of the 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 trial treatment). Of note, female patients should undergo a beta HCG test to demonstrate pregnancy status. A male patient who does not agree to use appropriate contraception, e.g., the barrier method and a total abstinence, during the trial until 3 months passed after the completion of the trial.
15)A patient who has psychiatric disease considered to be a potential concern from the viewpoints of follow up and protocol adherence.
16)A patient who was given autografting or allografting of organ or tissue (receiving an immunosuppressant).
17)A patient who has 10% shorter PT (%) compared to the lower limit of the institutional reference or 1.5 fold longer APTT compared to the upper limit of the institutional reference at screening.
18)A patient who showed positive reaction to any of HBs antigen, HCV antibody, or HIV 1 or HIV 2 antibody at screening. However, even if it is positive for HCV antibody, it should not be excluded when HCV RNA
test is negative.
19) A patient who is ineligible for the trial for other reasons in the opinion of the investigator or the subinvestigator.

Related Information

• Primary Sponsor: TANEMURA ATSUSHI
• Secondary Sponsor: KURODA KENSEI,ISHIHARA SANGYO KAISHA,LTD
• Secondary ID(s): NCT03818893,JapicCTI-194618