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

IO Biotech

Status and phase: Completed; Phase 2; Phase 1

Conditions: NSCLC

Treatments: Drug: Pemetrexed (Pemetrexed Alvogen); Biological: pembrolizumab (Keytruda); Biological: IO102; Drug: Carboplatin (Carboplatin Kabi)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03562871

IO102-012 / KN-764

2018-000139-28 (EudraCT Number)

KEYNOTE-764 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 109 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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109 participants in 4 patient groups

Cohort A1

Experimental group

Description:

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

Treatment:

Biological: IO102

Biological: pembrolizumab (Keytruda)

Cohort A2

Active Comparator group

Description:

Drug: pembrolizumab (Keytruda) 200 mg IV infusion on Day 1 of each 3 week cycle

Treatment:

Biological: pembrolizumab (Keytruda)

Cohort B1

Experimental group

Description:

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

Treatment:

Drug: Carboplatin (Carboplatin Kabi)

Biological: IO102

Drug: Pemetrexed (Pemetrexed Alvogen)

Biological: pembrolizumab (Keytruda)

Cohort B2

Active Comparator group

Description:

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

Treatment:

Drug: Carboplatin (Carboplatin Kabi)

Drug: Pemetrexed (Pemetrexed Alvogen)

Biological: pembrolizumab (Keytruda)