Clinical trial NCT02818426: Universal Cancer Peptide-based Vaccination in Metastatic NSCLC
Official title: Anticancer Therapeutic Vaccination Using Telomerase-derives Universal Cancer Peptides in Metastatic Non Small Cell Lung Cancer : A Phase I/II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Non-small Cell Lung Cancer
Keywords: cancer immunotherapy
CD4 T lymphocyte helper
telomerase
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
Collaborators: name: Invectys
First posted: 2016-06-29
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicity (DLT) of UCPVax (phase I)
timeFrame: until day 57 after the first vaccination
measure: Dose-related immunogenicity (phase II)
timeFrame: at day 73
Secondary outcomes:
measure: Tumor response
timeFrame: every 8 weeks up to 15 months
measure: Progression-free survival (PFS)
timeFrame: through study completion, an average of 2 years
measure: Overall survival (OS)
timeFrame: through study completion, an average of 2 years
measure: Health related Quality of Life (QoL)
timeFrame: through study completion, an average of 2 years
measure: Adverse Events according to NCI CTCAE v.4.03
timeFrame: through study completion, an average of 2 years
Other outcomes:
Locations:
city: Besancon
country: France
facility: Centre Hospitalier Régional Universitaire de Besançon
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Mulhouse
country: France
facility: Hôpital Emile Muller
city: Paris
country: France
facility: St Louis Hospital
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
Study officials:
References:
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.
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.
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.
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.
citation: 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.
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, Moltenis M, Limat S, Quoix E, Mascaux C, Debieuvre D, Fagnoni-Legat C, Borg C, Westeel V. Safety, Immunogenicity, and 1-Year Efficacy of Universal Cancer Peptide-Based Vaccine in Patients With Refractory Advanced Non-Small-Cell Lung Cancer: A Phase Ib/Phase IIa De-Escalation Study. J Clin Oncol. 2023 Jan 10;41(2):373-384. doi: 10.1200/JCO.22.00096. Epub 2022 Sep 7.