IO102 With Pembrolizumab, With or Without Chemotherapy, as First-line Treatment of Metastatic NSCLC

NSCLC Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03562871
• Other study ID #: IO102-012 / KN-764
• Secondary ID: 2018-000139-28KE
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 22, 2018
• Est. completion date: April 12, 2022

Study information

• Verified date: April 2022
• Source: IO Biotech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 109
• Est. completion date: April 12, 2022
• Est. primary completion date: February 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• NSCLC

Intervention

Biological:
• IO102
test immunotherapy
• pembrolizumab (Keytruda)
anti-PD-1 immunotherapy

Drug:
• Carboplatin (Carboplatin Kabi)
chemotherapy
• Pemetrexed (Pemetrexed Alvogen)
chemotherapy

Locations

Country	Name	City	State
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg	Community Of Heidelberg
Germany	PIUS Hospital Oldenburg	Oldenburg
Netherlands	Stichting Het Nederlands Kanker Instituut	Amsterdam	Community Of Amsterdam
Spain	Hospital Universitario de Vall d'Hebron	Barcelona	Catalonia
Spain	Insituto Oncologico Dr Rosell. Hospital Universitario Quiron Dexeus	Barcelona	Catalonia
Spain	Hospital Universitari de Girona Doctor Josep Trueta	Girona	Catalonia
Spain	Hospital Puerta del Hierro Majadahonda	Madrid	Community Of Madrid
Spain	Hospital Universitario 12 Octubre	Madrid	Community Of Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid	Community Of Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid	Community Of Madrid
Spain	Servicio de Oncología-El médico del Virgen de la Victoria	Málaga	Andalusia
Spain	Hospital Clinico Universitario de València	València	Horta De València
United Kingdom	Guy's Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
IO Biotech	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

Germany,  Netherlands,  Spain,  United Kingdom, 

References & Publications (4)

Andersen MH. Immune Regulation by Self-Recognition: Novel Possibilities for Anticancer Immunotherapy. J Natl Cancer Inst. 2015 Jun 10;107(9). pii: djv154. doi: 10.1093/jnci/djv154. Print 2015 Sep. — View 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. — View 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. — View Citation

Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fülöp 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. Epub 2016 Oct 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 (safety run-in)	Dose Limiting Toxicity graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03	One cycle i.e. 3 weeks
Primary	Phase 2 (efficacy)	Objective Response Rate (ORR) evaluated by RECIST 1.1 and defined as the rate of complete response (CR) + partial response (PR)	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	ORR	by baseline PD-L1 expression	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)