Clinical trial NCT06564623: Targeting Driver Oncogenes With a Peptide Vaccine Plus Durvalumab and Tremelimumab for Patients With Biliary Tract Cancers (BTC)
Official title: A Pilot Study of Targeting Driver Oncogenes With a Peptide Vaccine Plus Durvalumab and Tremelimumab for Patients With Biliary Tract Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Biliary Tract Cancers
Keywords: Biliary Tract Cancer
Duvalumab
Tremelimumab
Immunotherapy
mBTCvax (peptide vaccine + Poly-ICLC (Hiltonol))
Anti PD-L1
Anti-Cytotoxic T-lymphocyte antigen 4 (CTLA-4)
Hiltonol
Carcinoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Private Philanthropic Funds
First posted: 2024-08-21
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and the immune response of personalized mutant peptide vaccine with poly-ICLC adjuvant (mBTCvax) in combination with durvalumab and tremelimumab following front-line treatment in patients with advanced stage BTC.


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years
* Must have a histologically- or cytologically, proven biliary tract cancer (BTC) previously treated with gemcitabine/cisplatin/anti-PD(L)1 therapy.
* Must have evidence of radiological disease, must accept to have a tumor biopsy of an accessible lesion at baseline and on treatment.
* Must have sufficient archival tumor tissue for next-generation sequencing (NGS) and immune-phenotyping.
* Have a BTC containing at least one of the oncogenic mutation/alterations targeted by the vaccine.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Must have body weight of \>30 kg.
* Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
* Patients with chronic or acute hepatitis B virus (HBV) or hepatitis C virus (HCV) infection must have disease controlled prior to enrollment.
* Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test.
* For both Women and Men, must use acceptable form of birth control while on study.
* Must have a life expectancy of at least 12 weeks.
* Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

* Participation in another clinical study with an investigational product during the last 2 weeks.
* Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study.
* Any of the following procedures or medications within 2 weeks prior to initiation of study treatment:

  * Systemic or topical steroids at immunosuppressive doses (\> 10 mg/day of prednisone or equivalent). The following are exceptions to this criterion:
  * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  * Palliative or adjuvant radiation or gamma knife radiosurgery.
  * Chemotherapy or checkpoint inhibitor targeting anti-Pd1/PD-L1.
* Within 4 weeks prior to initiation of study treatment:

  * Any investigational cytotoxic drug.
  * Any investigational device.
  * Non-oncology vaccines containing live virus.
  * Allergen hyposensitization therapy.
  * Growth factors, e.g. granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin.
  * Major surgery.
* Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
* Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
* All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
* Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy.
* Patients with a history of prior treatment with anti-PD-1 and anti-PD-L1.
* History of severe hypersensitivity reaction to any monoclonal antibodies or related compounds or to any of its components.
* History of leptomeningeal carcinomatosis.
* Patient has a known history or evidence of brain metastases.
* Has an active known or suspected autoimmune disease or which has required systemic therapy in the last 5 years.
* Known history of interstitial lung disease or of (non-infectious) pneumonitis that required steroids or current pneumonitis.
* Has a pulse oximetry \< 92% on room air.
* Requires the use of home oxygen.
* Has a known history of Human Immunodeficiency Virus (HIV)/AIDS
* Has active co-infection with HBV (hepatitis B virus) and HCV (hepatitis C virus) or coinfected with HBV and hepatitis delta virus (HDV)
* Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients who have been diagnosed with another cancer or myeloproliferative disorder in the past 5 years requiring systemic therapy or expected to require active therapy within the clinical study period.
* Has a diagnosis of immunodeficiency.
* Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded.
* Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
* Patient is at the time of signing informed consent a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
* Patient is unwilling or unable to follow the study schedule for any reason.
* Pregnant or breastfeeding.
* WOCBP and men with female partners (WOCBP) who are not willing to use contraception.
* Evidence of clinical ascites requiring paracentesis in the last 4 weeks.
* History of malignant bowel obstruction.

Primary outcomes:
measure: Number of participants experiencing grade 3 or above drug-related toxicities
timeFrame: 20 Months
measure: Maximum percentage change in interferon-producing mutant-specific cluster of differentiation 8 (CD8) and cluster of differentiation 4 (CD4) T cells.
timeFrame: Baseline to 20 weeks post vaccination (baseline, 20 weeks)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 4 years
measure: Overall Survival (OS)
timeFrame: 4 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: SKCCC Johns Hopkins Medical Institution
state: Maryland
Study officials:
affiliation: SKCCC Johns Hopkins Medical Institution
name: Marina Baretti, MD
role: PRINCIPAL_INVESTIGATOR
References: