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

  • STATUS
    Recruiting
  • End date
    Jun 30, 2022
  • participants needed
    46
  • sponsor
    Osaka University
Updated on 22 January 2021

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.

Description

  1. Primary Objective & Hypothesis
    1. Objective: Efficacy of the combination therapy The combination therapy with intracutaneous injections of GEN0101 + intravenous infusions of Pembrolizumab is given to patients with confirmed SD or unconfirmed PD after anti-PD-1 antibody therapy. When the last subject completes Week 13 (Day 85th), the RECIST v1.1-based antitumor effect is assessed for all the subjects up to Week 17 (Day 113th) and then the ORR is calculated in both treatment groups, which are tested to examine the significant difference to historical data of KEYNOTE-002.
    2. Hypothesis: The antitumor effect and the induction of antitumor immunity of the combination therapy would be enhanced.
    3. Secondary Objectives & Hypothesises
    4. Objectives: Efficacy and safety of the combination therapy The combination therapy with intracutaneous injections of GEN0101 + intravenous infusions of Pembrolizumab is given to patients with confirmed SD or unconfirmed PD after anti-PD-1 antibody therapy.

When the last subject completed Week 17 (Day 113th), antitumor effect in Week 13 (Day 85th, unconfirmed) and Week 17 (Day 113th, confirmed) is assessed based on RECIST v1.1, irRC, and irRECIST for all subjects and then the ORR is calculated. Likewise, changes in individual tumor sizes in Week 13 (Day 85th, unconfirmed) and Week 17 (Day 113th, confirmed) are measured, and then percent changes in tumor sizes (percent tumor shrinkage or growth) are calculated. In each subject, the induction of antitumor immunity in Week 13 (Day 85th) is investigated with the index of activated NK cells in peripheral blood.

When the last subject completed Week 53 (Day 365th), antitumor effect is assessed for all the subjects based on OS and RECIST v1.1, irRC, and irRECIST-based ORR, BOR and PFS, which are tested to examine significant difference to historical data of KEYNOTE-002.

When the last subject completed Week 105 (Day 729th), antitumor effect is assessed for all the subjects based on OS and RECIST v1.1, irRC, and irRECIST-based ORR, BOR and PFS, which are tested to examine significant difference to historical data of KEYNOTE-002.

On the basis of these results, the antitumor effect and the induction of antitumor immunity of the combination therapy is investigated. These are secondary objectives in the trial.

As another secondary objective, AEs are investigated in all the subjects for safety evaluation of the combination therapy until the last subject completed Week 105 (Day 729th).

2. Hypothesis: The antitumor effect and the induction of antitumor immunity of the combination therapy would be enhanced and the safety would be acceptable.

3. Exploratory Objective Objective: Storage and use of samples for future exploratory evaluation

Details
Condition Advanced Melanoma
Treatment Combination of GEN0101 and Pembrolizmub
Clinical Study IdentifierNCT03818893
SponsorOsaka University
Last Modified on22 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 20 yrs and 85 yrs?
Gender: Male or Female
Do you have any of these conditions: Do you have Advanced Melanoma??
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/L and neutrophil count over 1,500/L (2)Platelet count over over 75,000/L (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

Exclusion Criteria

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)
Patient has psychiatric disease considered to be a potential concern from the viewpoints of follow-up and protocol adherence
Patient had given autografting or allografting of organ or tissue (receiving an immunosuppressant)
Patient has over 10%-shorter prothrombin time (PT) compared to lower limit of normal (LLN) or over 1.5-fold longer activated partial thromboplastin time (APTT) compared to ULN at screening
Patient has showed positive reaction to any of HBs antigen, HCV antibody, HIV-1 antibody, 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
Patient is considered ineligible for this trial by the investigator or the sub-investigators
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note