Clinical trial NCT03562871: IO102 With Pembrolizumab, With or Without Chemotherapy, as First-line Treatment of Metastatic NSCLC
Official title: An Open-label, Randomized, Phase I/II Trial Investigating the Safety and Efficacy of IO102 in Combination With Pembrolizumab, With or Without Chemotherapy, as First-line Treatment for Patients With Metastatic Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: NSCLC
Keywords: PD-1
PD-L1
Programmed Cell Death 1
Chemotherapy
Pemetrexed
Carboplatin
Pembrolizumab
Immunotherapy
IO102
Keytruda
Lead sponsor: IO Biotech
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2018-06-20
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if IO102 combined with pembrolizumab with or without chemotherapy is safe tolerable and effective in the treatment of Non-small Cell Lung Carcinoma (NSCLC).

The hypothesis is that IO102 will improve the objective response rate (ORR) in patients with metastatic NSCLC.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed metastatic NSCLC or non squamous NSCLC
* Have biomarker-positive solid tumor
* Male participants of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication
* Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication
* The participant must provide written informed consent
* Have measurable disease per RECIST 1.1
* Have provided a blood sample and archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
* Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
* Adequate organ function

Exclusion Criteria:

* Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related AE (irAE)
* Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
* Radiotherapy within 2 weeks of start of trial treatment
* Vaccination with a live vaccine within 30 days prior to the first dose of trial treatment.Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
* Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of trial treatment.
* Has a known additional malignancy that is progressing or has required active treatment within the past 2 years.
* Has known active CNS metastases and/or carcinomatous meningitis.
* Has severe hypersensitivity (≥Grade 3) to IO102, pembrolizumab, carboplatin, pemetrexed and/or any of its excipients.
* Has an active autoimmune disease that has required systemic treatment in past 2 years.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy.
* Has a known history of human immunodeficiency virus (HIV) infection.
* Known active Hepatitis B or Hepatitis C
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial.

Primary outcomes:
measure: Phase 1 (safety run-in)
timeFrame: One cycle i.e. 3 weeks
measure: Phase 2 (efficacy)
timeFrame: From date of randomization until date of death from any cause, withdrawal of consent or loss to follow up whichever came first, assessed for up to 35 cycles (2 years)
Secondary outcomes:
measure: ORR
timeFrame: From date of randomization until date of death from any cause, withdrawal of consent or loss to follow up whichever came first, assessed for up to 35 cycles (2 years)
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
state: Community Of Heidelberg
city: Oldenburg
country: Germany
facility: PIUS Hospital Oldenburg
city: Amsterdam
country: Netherlands
facility: Stichting Het Nederlands Kanker Instituut
state: Community Of Amsterdam
city: Málaga
country: Spain
facility: Servicio de Oncología-El médico del Virgen de la Victoria
state: Andalusia
city: Barcelona
country: Spain
facility: Insituto Oncologico Dr Rosell. Hospital Universitario Quiron Dexeus
state: Catalonia
city: Barcelona
country: Spain
facility: Hospital Universitario de Vall d'Hebron
state: Catalonia
city: Girona
country: Spain
facility: Hospital Universitari de Girona Doctor Josep Trueta
state: Catalonia
city: Madrid
country: Spain
facility: Hospital Universitario 12 Octubre
state: Community Of Madrid
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
state: Community Of Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
state: Community Of Madrid
city: Madrid
country: Spain
facility: Hospital Puerta del Hierro Majadahonda
state: Community Of Madrid
city: València
country: Spain
facility: Hospital Clinico Universitario de València
state: Horta De València
city: London
country: United Kingdom
facility: Guy's Hospital
Study officials:
affiliation: Guy's Hospital
name: James Spicer, MD Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Langer CJ, Gadgeel SM, Borghaei H, Papadimitrakopoulou VA, Patnaik A, Powell SF, Gentzler RD, Martins RG, Stevenson JP, Jalal SI, Panwalkar A, Yang JC, Gubens M, Sequist LV, Awad MM, Fiore J, Ge Y, Raftopoulos H, Gandhi L; KEYNOTE-021 investigators. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016 Nov;17(11):1497-1508. doi: 10.1016/S1470-2045(16)30498-3. Epub 2016 Oct 10.
citation: Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. doi: 10.1056/NEJMoa1606774. Epub 2016 Oct 8.
citation: Iversen TZ, Engell-Noerregaard L, Ellebaek E, Andersen R, Larsen SK, Bjoern J, Zeyher C, Gouttefangeas C, Thomsen BM, Holm B, Thor Straten P, Mellemgaard A, Andersen MH, Svane IM. Long-lasting disease stabilization in the absence of toxicity in metastatic lung cancer patients vaccinated with an epitope derived from indoleamine 2,3 dioxygenase. Clin Cancer Res. 2014 Jan 1;20(1):221-32. doi: 10.1158/1078-0432.CCR-13-1560. Epub 2013 Nov 11.
citation: Andersen MH. Immune Regulation by Self-Recognition: Novel Possibilities for Anticancer Immunotherapy. J Natl Cancer Inst. 2015 Jun 10;107(9):djv154. doi: 10.1093/jnci/djv154. Print 2015 Sep.