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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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NSCLC

Intervention / Treatment
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* Biological: IO102
* Biological: pembrolizumab (Keytruda)
* Drug: Carboplatin (Carboplatin Kabi)
* Drug: Pemetrexed (Pemetrexed Alvogen)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A1<br>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<br>* test immunotherapy<br>Biological: pembrolizumab (Keytruda)<br>* anti-PD-1 immunotherapy<br>|
| Active Comparator: Cohort A2<br>Drug: pembrolizumab (Keytruda) 200 mg IV infusion on Day 1 of each 3 week cycle | Biological: pembrolizumab (Keytruda)<br>* anti-PD-1 immunotherapy<br>|
| Experimental: Cohort B1<br>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<br>* test immunotherapy<br>Biological: pembrolizumab (Keytruda)<br>* anti-PD-1 immunotherapy<br>Drug: Carboplatin (Carboplatin Kabi)<br>* chemotherapy<br>Drug: Pemetrexed (Pemetrexed Alvogen)<br>* chemotherapy<br>|
| Active Comparator: Cohort B2<br>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)<br>* anti-PD-1 immunotherapy<br>Drug: Carboplatin (Carboplatin Kabi)<br>* chemotherapy<br>Drug: Pemetrexed (Pemetrexed Alvogen)<br>* chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-1, PD-L1, Programmed Cell Death 1, Chemotherapy, Pemetrexed, Carboplatin, Pembrolizumab, Immunotherapy, IO102, Keytruda