Universal Cancer Peptide-based Vaccination in Metastatic NSCLC

Metastatic Non-small Cell Lung Cancer Clinical Trial

— UCPVax  

Official title:

Anticancer Therapeutic Vaccination Using Telomerase-derives Universal Cancer Peptides in Metastatic Non Small Cell Lung Cancer : A Phase I/II Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02818426
• Other study ID #: UCPVax
• Secondary ID: 2015-001712-35
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 20, 2016
• Est. completion date: December 20, 2023

Study information

• Verified date: July 2023
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

UCPVAx is a therapeutic vaccine based on the telomerase-derived UCP designed to induce strong TH1 CD4 T cell responses in cancer patients.

Three doses of UCPVax (0,25 mg, 0,5 mg and 1 mg) will be tested in this phase I/II study by using Continuous Reassessment Method (CRML) dose escalation design model.

The phase I is a dose escalation study designed to evaluate safety of use of UCPVax and to estimate its Maximum Tolerated Dose (MTD).

The phase II is a dose deescalation designed to evaluate the immunogenicity of UCPVax according to the dose level.

Description:

UCPVax study is a prospective multicenter phase I/II study: 54 patients with metastatic NSCLC will be enrolled in 5 centers in France.

A translational research program will be performed to better define the eligibility criteria and predictive biomarkers needed for randomized phase II and Phase III trials.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 54
• Est. completion date: December 20, 2023
• Est. primary completion date: August 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

Inclusion Criteria:

• Written informed consent

• Histologically or cytologically confirmed NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma, undifferentiated carcinoma or other)

• Stage IIIB not amenable to radiotherapy or stage IV cancer according to the TNM classification (7th edition) or recurrent NSCLC after surgery not amenable to loco-regional therapy.

• Pre-treated with at least 2 or 3 lines of treatment (including immunotherapy). Chemoradiation for stage IIIB disease is considered as one treatment line.

• At least one measurable lesion by CT scan or MRI based on RECIST criteria version 1.1

• Performance status 0 or 1 on the ECOG scale

• Life-expectancy > 3 months

• Adequate hematological, hepatic, and renal function

Exclusion Criteria:

• Prior history of other malignancy except for: basal cell carcinoma of the skin, cervical intra-epithelial neoplasia and other cancer curatively treated with no evidence of disease for at least 5 years

• Symptomatic brain metastases. Patients with controlled brain metastases after radiation therapy or with asymptomatic brain metastases may be included.

• History of active autoimmune diseases (lupus, rheumatoid arthritis, inflammatory bowel disease…)

• Patients under chronic treatment with systemic corticoids or other immunosuppressive drugs (prednisone or prednisolone = 10 mg/day is allowed) - - Positive serology for Human Immunodeficiency Virus (HIV) or Hepatitis C virus (HCV); presence in the serum of the antigens HBs

• Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment

• Pregnancy or lactating patients.

• Patients with any medical or psychiatric condition or disease,

• Patients under guardianship, curatorship or under the protection of justice.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Metastatic Non-small Cell Lung Cancer

Intervention

Drug:
• UCPVax

Locations

Country	Name	City	State
France	Centre Hospitalier Régional Universitaire de Besançon	Besancon
France	Centre Georges François Leclerc	Dijon
France	Hôpital Emile Muller	Mulhouse
France	St Louis Hospital	Paris
France	Hôpitaux Universitaires de Strasbourg	Strasbourg

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon	Invectys

Country where clinical trial is conducted

France, 

References & Publications (6)

Adotevi O, Dosset M, Galaine J, Beziaud L, Godet Y, Borg C. Targeting antitumor CD4 helper T cells with universal tumor-reactive helper peptides derived from telomerase for cancer vaccine. Hum Vaccin Immunother. 2013 May;9(5):1073-7. doi: 10.4161/hv.23587. Epub 2013 Jan 28. — View Citation

Adotevi O, Vernerey D, Jacoulet P, Meurisse A, Laheurte C, Almotlak H, Jacquin M, Kaulek V, Boullerot L, Malfroy M, Orillard E, Eberst G, Lagrange A, Favier L, Gainet-Brun M, Doucet L, Teixeira L, Ghrieb Z, Clairet AL, Guillaume Y, Kroemer M, Hocquet D, M — View Citation

Dosset M, Godet Y, Vauchy C, Beziaud L, Lone YC, Sedlik C, Liard C, Levionnois E, Clerc B, Sandoval F, Daguindau E, Wain-Hobson S, Tartour E, Langlade-Demoyen P, Borg C, Adotevi O. Universal cancer peptide-based therapeutic vaccine breaks tolerance against telomerase and eradicates established tumor. Clin Cancer Res. 2012 Nov 15;18(22):6284-95. doi: 10.1158/1078-0432.CCR-12-0896. Epub 2012 Oct 2. — View Citation

Galaine J, Borg C, Godet Y, Adotevi O. Interest of Tumor-Specific CD4 T Helper 1 Cells for Therapeutic Anticancer Vaccine. Vaccines (Basel). 2015 Jun 30;3(3):490-502. doi: 10.3390/vaccines3030490. — View Citation

Godet Y, Dosset M, Borg C, Adotevi O. Is preexisting antitumor CD4 T cell response indispensable for the chemotherapy induced immune regression of cancer? Oncoimmunology. 2012 Dec 1;1(9):1617-1619. doi: 10.4161/onci.21513. — View Citation

Godet Y, Fabre E, Dosset M, Lamuraglia M, Levionnois E, Ravel P, Benhamouda N, Cazes A, Le Pimpec-Barthes F, Gaugler B, Langlade-Demoyen P, Pivot X, Saas P, Maillere B, Tartour E, Borg C, Adotevi O. Analysis of spontaneous tumor-specific CD4 T-cell immunity in lung cancer using promiscuous HLA-DR telomerase-derived epitopes: potential synergistic effect with chemotherapy response. Clin Cancer Res. 2012 May 15;18(10):2943-53. doi: 10.1158/1078-0432.CCR-11-3185. Epub 2012 Mar 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity (DLT) of UCPVax (phase I)	The following adverse events graded according to CTCAE v 4.03 will be classified as DLTs : Hematologic: Grade 4 neutropenia (ANC <0.5 x 109/L) lasting >5 days; Febrile neutropenia (defined as neutropenia =Grade 3 [ANC <1000 cells/mm3] and a body temperature =38.5°C); Grade =3 thrombocytopenia (<50.0 - 25.0 x 109/L) with bleeding; Grade 4 thrombocytopenia (<25.0 x 109/L) >5 days; Grade 4 anemia (hemoglobin <6.5 g/dL or 4.0 nmol/L); Non-hematologic: o Grade =3 toxicities, except for alopecia and those grade 3 events that respond to treatment (eg. grade 3 nausea, vomiting, diarrhea that responds to standard medical supportive care within 48 hours will not be considered a DLT).; Immune system disorder: Grade =2 allergic reaction (except for local reaction at the injection site : grade = 3); Grade =2 autoimmune disease (colitis, thyroidis…); Grade =2 cytokine release syndrome (nausea, headache, tachycardia, hypotension, rash and shortness of breath)	until day 57 after the first vaccination
Primary	Dose-related immunogenicity (phase II)	Antigen-specific T cell responses measured using IFN-gamma ELISPOT.	at day 73
Secondary	Tumor response	Tumor response evaluated per RECIST v1.1.	every 8 weeks up to 15 months
Secondary	Progression-free survival (PFS)	delay from the date of inclusion to the disease progression (RECIST) or death from any cause whichever occurs first,	through study completion, an average of 2 years
Secondary	Overall survival (OS)	delay from the date of inclusion to death from any cause.	through study completion, an average of 2 years
Secondary	Health related Quality of Life (QoL)	HrQoL will be assessed using EORTC QLQ-C30 and LC13 modules specific to lung cancer	through study completion, an average of 2 years
Secondary	Adverse Events according to NCI CTCAE v.4.03		through study completion, an average of 2 years