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

NCT03047928 | Completed Phase 1 Results DMC

• 1 other identifier: MM1636
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  Determine the safety of the combination therapy of Nivolumab and the PD-L1/IDO peptide vaccine for patients with metastatic melanoma by reporting adverse events according to CTCAE v. 4.0.

  0 - 75 weeks

Secondary Outcomes (4)

• Objective Response Rate

  The patients were evaluated every 12 weeks until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 58 months

• Overall Survival

  The patients were evaluated from the date of first study treatment until the date of death from any cause, assessed up to 58 months

• Progression Free Survival

  The patients were evaluated from date of first study treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 58 months

• Evaluation of Vaccine-specific Responses in Peripheral Blood Mononuclear Cells (PBMCs)

  At baseline and up to 24 months after inclusion

Study Arms (1)

Patient group

EXPERIMENTAL

All patients receive the same treatment. Patients included in the protocol are treated with Nivolumab according to usual guidelines, implying outpatient IV infusions of 3 mg/kg biweekly until progression. The vaccine is administered on the same day as the administration start of Nivolumab. The vaccination is given biweekly for a total of 6 times, then every fourth week up to week 47, whereupon no additional vaccines will be given. In total, 15 vaccines will be administered. A vaccine consist of 100 μg IDO long peptide, 100 μg PD-L1 long1 peptide and 500 microliters Montanide as adjuvant. Patients who complete all vaccines will continue Nivolumab treatment after standard guidelines.

Drug: Nivolumab; Biological: PD-L1/IDO peptide vaccine

Interventions

Nivolumab DRUG

Nivolumab 3 mg/kg is administered biweekly as long as there is clinical benefit.

Also known as: Opdivo

Patient group

PD-L1/IDO peptide vaccine BIOLOGICAL

The vaccine is administered biweekly for a total of 6 times, then every fourth week up to 47 weeks, whereupon no additional vaccinations will be given. A total of 15 vaccines will be administered. A vaccine consists of 100 μg PD-L1 long1 peptide, 100 μg IDO long peptide and 500 μl Montande as adjuvant.

Also known as: IO102/IO103 peptide vaccine

Patient group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Inge Marie Svane: lead

Study Sites (2)

Herlev Hospital

Herlev, 2730, Denmark

Location

National Center for Cancer Immune Therapy, Dept. of Oncology

Herlev, 2730, Denmark

Location

Related Publications (2)

• Lorentzen CL, Kjeldsen JW, Ehrnrooth E, Andersen MH, Marie Svane I. Long-term follow-up of anti-PD-1 naive patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab. J Immunother Cancer. 2023 May;11(5):e006755. doi: 10.1136/jitc-2023-006755.

  PMID: 37217243 DERIVED

• Kjeldsen JW, Lorentzen CL, Martinenaite E, Ellebaek E, Donia M, Holmstroem RB, Klausen TW, Madsen CO, Ahmed SM, Weis-Banke SE, Holmstrom MO, Hendel HW, Ehrnrooth E, Zocca MB, Pedersen AW, Andersen MH, Svane IM. A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma. Nat Med. 2021 Dec;27(12):2212-2223. doi: 10.1038/s41591-021-01544-x. Epub 2021 Dec 9.

  PMID: 34887574 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Prof. MD, Inge Marie Svane
• Organization: CCIT-DK

inge.marie.svane@regionh.dk

38683868

Study Officials

• Inge Marie Svane, Prof., MD

  National Center for Cancer Immune Therapy, Dept. of Oncology, Copenhagen University Hospital Herlev, Borgmester Ib Juuls vej 1, DK-2730

  STUDY DIRECTOR

• Cathrine Lund Lorentzen, MD

  National Center for Cancer Immune Therapy, Dept. of Oncology, Copenhagen University Hospital Herlev, Borgmester Ib Juuls vej 1, DK-2730

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Professor

Study Record Dates

• First Submitted: February 6, 2017
• First Posted: February 9, 2017
• Study Start: February 22, 2018
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: February 20, 2025
• Results First Posted: February 20, 2025

Record last verified: 2025-02

Locations

DK (2)