Combination Therapy With Nivolumab and PD-L1/IDO Peptide Vaccine to Patients With Metastatic Melanoma

  • STATUS
    Recruiting
  • days left to enroll
    54
  • participants needed
    50
  • sponsor
    Inge Marie Svane
Updated on 7 October 2022

Summary

Combination therapy is becoming more and more general in the treatment of oncological diseases. In this clinical trial combination the standard immunotherapeutic treatment; the programmed death 1 (PD-1) regulatory antibody Nivolumab and a peptide vaccine consisting of programmed death ligand 1 (PD-L1) and Indoleamine 2,3-dioxygenase (IDO) peptides will be tested in patients with metastatic melanoma. Patients will be treated with Nivolumab every second week as long as there is clinical benefit. The PD-L1/IDO peptide vaccine is given from start of Nivolumab and every second week for the first 6 vaccines and thereafter every fourth week up to 1 year.

Description

Background

Huge advances have been made in the treatment of metastatic melanoma (MM) the past 5 years. Especially immunotherapy has shown promising results.

Cancer cells are naturally attacked by cells of the immune system, but can induce a state of tolerance whereby they escape from immune attack. This escape is brought about by many mechanisms. An important one is the programmed death pathway (PD-1/PD-L1). PD-L1 is commonly overexpressed on cancer cells. Interaction of PD-1 on activated T cells and PD-L1 on cancer cells lead to inhibition of the cytotoxic T cells. Another important mechanism is through overexpression of the metabolic enzyme IDO on cancer cells. Activation of IDO also inhibits cytotoxic T cells.

Investigators have recently identified spontaneous T cell reactivity against PD-L1 and IDO in the tumor microenvironment and in the peripheral blood of patients with MM and healthy donors. Both IDO and PD-L1 reactive CD8 T cells are cytotoxic and can kill cancer cells and immune regulatory cells in vitro.. Thus boosting specific T cells that recognize immune regulatory proteins such as IDO and PD-L1 may directly modulate immune regulation.

Due to distinct mechanisms of action, the combination of treatment with a monoclonal antibody targeting PD-1 (Nivolumab) and a vaccine with peptides against PD-L1 and IDO may have a synergistic effect.

Investigators have previously reported a phase I trial where, the IDO peptide was tested in 15 patients with MM in combination with Ipilimumab, and no grade 3-4 toxicity was seen. The PD-L1 peptide is currently being tested in a first-in-man study in patients with multiple myeloma.

Methods

A two-step clinical phase I/II trial design will be used, starting out with a pilot study including 6 patients with MM to test feasibility and tolerability. If the treatment is found feasible the study will be extended to a phase II study with 24 patients. The objective is to describe anti-tumor immune responses and objective responses using RECIST 1.1.

Patients will be treated with Nivolumab in accordance with standard regimen, which involves outpatient IV infusions every second week as long as there is clinical benefit. The PD-L1/IDO peptide vaccine is given from start of Nivolumab and every second week for the first 6 vaccines and thereafter every fourth week up to 1 year. 15 vaccines will be administered in total.

Patients will be followed with clinical controls and diagnostic imaging every 12 weeks. Patients who receive all vaccines will have follow up after 3 and 6 months in parallel with standard of care treatment for Nivolumab.

Details
Condition Metastatic Melanoma
Treatment Nivolumab, PD-L1/IDO peptide vaccine
Clinical Study IdentifierNCT03047928
SponsorInge Marie Svane
Last Modified on7 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Age ≥ 18
The patient has unrespectable or metastatic melanoma with progressive, persistent or recurrent disease on or following treatment with standard of care agents
Patients belonging to one of the following patient groups will be enrolled
Cohort A: Anti PD-1/PD-L1 naïve patients (30 patients). The patient is a
candidate for Nivolumab monotherapy. Prior anti-PD-1/anti-PD-L1 antibody
treatment is not allowed
OR Cohort B: Extension cohort (10 patients). Progressive disease ON anti-PD-1
monotherapy.Subjects should not have experienced serious and/or life-
threatening toxicity to antibody therapy
OR Cohort C: Extension cohort (10 patients). Progressive disease during follow
up OFF anti-PD-1 after clinical benefit (SD/PR/CR) on anti-PD-1 therapy
Subjects should not have discontinued antibody therapy due to serious and/or
lifethreatening toxicity
At least one measurable parameter according to RECIST 1.1
The patient has an ECOG performance status of 0 or 1
The patient is a female of childbearing potential with negative pregnancy test
For women: Agreement to use contraceptive methods with a failure rate of < 1 % per year during the treatment period and for at least 120 days after the treatment
For men: Agreement to use contraceptive measures and agreement to refrain from donating sperm
The patient has met the following hematological and biochemical criteria
AST and ALT ≤2,5 X ULN or ≤5 X ULN with liver metastases
Serum total bilirubin ≤1,5 X ULN or direct bilirubin ≤ ULN for patient with total bilirubin level > 1,5 ULN
Serum creatinine ≤1,5 X ULN
ANC (Absolute Neutrophil Count) ≥1,000/mcL
Platelets ≥ 75,000 /mcL
Hemoglobin ≥ 9 g/dL eller ≥ 5.6 mmol/L
Signed declaration of content after oral and written information about the protocol

Exclusion Criteria

The patient has not recovered to grade 0-1 from adverse events due to prior chemotherapy, radioactive or biological cancer therapy
The patient has not recovered from surgery or is less than 4 weeks from major surgery
The patient has a history of life-threatening or severe immune related adverse events on treatment with another immunotherapy and is considered to be at risk of not recovering
The patient is expected to require any other form of systemic antineoplastic therapy while receiving the treatment
The patient has a history of severe clinical autoimmune disease
The patient has a history of pneumonitis, organ transplant, human immunodeficiency virus positive, active hepatitis B or hepatitis C
The patient requires systemic steroids for management of immune-related adverse events experienced on another immunotherapy
The patient has active CNS metastases and/or carcinomatous meningitis. However, patients with subclinical brain metastases < 1 cm can be included (maximum of 4 metastases < 1 cm). (Patients with previously treated brain metastases may participate provided they are clinically stable. Patients with untreated brain metastasis will be excluded)
The patient has any condition that will interfere with patient compliance or safety (including but not limited to psychiatric or substance abuse disorders)
The patient is pregnant or breastfeeding
The patient is unable to voluntarily agree to participate by signed informed consent or assent
The patient has an active infection requiring systemic therapy
The patient has received a live virus vaccine within 30 days of planned start of therapy
Known side effects to Montanide ISA-51
Significant medical disorder according to investigator; e.g. severe asthma or chronic obstructive lung disease, dysregulated heart disease or dysregulated diabetes mellitus
Concurrent treatment with other experimental drugs
Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis etc
Severe allergy or anaphylactic reactions earlier in life
Clear my responses

How to participate?

Step 1 Connect with a study center
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

Primary Contact

site

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