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

Sponsor

IO Biotech (Industry)

Overall Status

Completed

CT.gov ID

NCT03562871

Collaborator

Merck Sharp & Dohme LLC (Industry)

109

Enrollment

Locations

Arms

43.7

Actual Duration (Months)

8.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
NSCLC	Biological: IO102 Biological: pembrolizumab (Keytruda) Drug: Carboplatin (Carboplatin Kabi) Drug: Pemetrexed (Pemetrexed Alvogen)	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

109 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 22, 2018

Actual Primary Completion Date :

Feb 6, 2021

Actual Study Completion Date :

Apr 12, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A1 Drug: IO102 100µg administered subcutaneously (SC) on Day 1 of each 3 week cycle PLUS Drug: pembrolizumab (Keytruda) 200 mg intravenous (IV) infusion on Day 1 of each 3 week cycle	Biological: IO102 test immunotherapy Biological: pembrolizumab (Keytruda) anti-PD-1 immunotherapy
Active Comparator: Cohort A2 Drug: pembrolizumab (Keytruda) 200 mg IV infusion on Day 1 of each 3 week cycle	Biological: pembrolizumab (Keytruda) anti-PD-1 immunotherapy
Experimental: Cohort B1 Drug: IO102 100µg SC on Day 1 of each 3 week cycle PLUS Drug: pembrolizumab (Keytruda) 200 mg IV on Day 1 of each 3 week cycle PLUS Drug: carboplatin (Carboplatin Kabi) at a target AUC of 5 mg/mL IV infusion on Day 1 of each 3 week cycle for a max of 4 administrations PLUS Drug: pemetrexed (Pemetrexed Alvogen) at 500 mg/m2 IV infusion on Day 1 of each 3 week cycle	Biological: IO102 test immunotherapy Biological: pembrolizumab (Keytruda) anti-PD-1 immunotherapy Drug: Carboplatin (Carboplatin Kabi) chemotherapy Drug: Pemetrexed (Pemetrexed Alvogen) chemotherapy
Active Comparator: Cohort B2 Drug: pembrolizumab (Keytruda) 200 mg IV on Day 1 of each 3 week cycle PLUS Drug: carboplatin (Carboplatin Kabi) at a target AUC of 5 mg/mL IV infusion on Day 1 of each 3 week cycle for a max of 4 administrations PLUS Drug: pemetrexed (Pemetrexed Alvogen) at 500 mg/m2 IV infusion on Day 1 of each 3 week cycle	Biological: pembrolizumab (Keytruda) anti-PD-1 immunotherapy Drug: Carboplatin (Carboplatin Kabi) chemotherapy Drug: Pemetrexed (Pemetrexed Alvogen) chemotherapy

Outcome Measures

Primary Outcome Measures

Phase 1 (safety run-in) [One cycle i.e. 3 weeks]
Dose Limiting Toxicity graded per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Phase 2 (efficacy) [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)]
Objective Response Rate (ORR) evaluated by RECIST 1.1 and defined as the rate of complete response (CR) + partial response (PR)

Secondary Outcome Measures

ORR [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)]
by baseline PD-L1 expression

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thoraxklinik Heidelberg gGmbH	Heidelberg	Community Of Heidelberg	Germany	69126
2	PIUS Hospital Oldenburg	Oldenburg		Germany	26121
3	Stichting Het Nederlands Kanker Instituut	Amsterdam	Community Of Amsterdam	Netherlands
4	Servicio de Oncología-El médico del Virgen de la Victoria	Málaga	Andalusia	Spain	29010
5	Insituto Oncologico Dr Rosell. Hospital Universitario Quiron Dexeus	Barcelona	Catalonia	Spain	08028
6	Hospital Universitario de Vall d'Hebron	Barcelona	Catalonia	Spain	08035
7	Hospital Universitari de Girona Doctor Josep Trueta	Girona	Catalonia	Spain	17007
8	Hospital Universitario 12 Octubre	Madrid	Community Of Madrid	Spain	28041
9	Hospital Universitario HM Sanchinarro	Madrid	Community Of Madrid	Spain	28050
10	Hospital Universitario Ramón y Cajal	Madrid	Community Of Madrid	Spain	28134
11	Hospital Puerta del Hierro Majadahonda	Madrid	Community Of Madrid	Spain
12	Hospital Clinico Universitario de València	València	Horta De València	Spain	46010
13	Guy's Hospital	London		United Kingdom	SE1 9RT