Nivolumab/Ipilimumab and Chemotherapy Combination in Advanced NSCLC Patients With HIV, HBV, HCV and Long Covid Syndrome

NCT05597800 | Not Yet Recruiting Phase 2

• 1 other identifier: 2022-002313-41
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

Study type: Phase 2 - Interventional Trial Number of patients to be enrolled: 105 Participating countries: Italy Study drugs: nivolumab and ipilimumab Cohort A: HBV and HCV patients Cohort B: HIV patients Cohort C: Long COVID syndrome The stratification factors are HBV/HCV positive (cohort A), HIV positive (cohort B), patients with Long Covid syndrome (Cohort C), histology (squamous vs non-squamous histology), and gender (male vs female).

Conditions

NSCLC Stage IV; HIV; HBV; HCV; Long COVID

Outcome Measures

Primary Outcomes (2)

• Safety, defined as onset of grade 3 or 4 (G3/4) treatment-related adverse events (TRAEs), assessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.

  The primary objectives of the study are safety, defined as onset of grade 3 or 4 (G3/4) treatment-related adverse events (TRAEs), assessed by the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.

  3 years

• Objective Response Rate (ORR) measured as for RECIST 1.1 criteria

  Activity in terms of objective response rate (ORR) of nivolumab plus ipilimumab in combination with platinum-based chemotherapy (2 cycles) in first-line advanced NSCLC patients with chronic viral infections.

  3 years

Secondary Outcomes (3)

• Overall survival (OS)

  3 years

• Progression-free survival (PFS)

  3 years

• Duration of response (DOR)

  3 years

Other Outcomes (1)

• Exploratory objectives

  4 years

Study Arms (3)

Cohort A: HBV and HCV patients

EXPERIMENTAL

Participants (≥ 18 years) must have histologically confirmed metastatic or unresectable non-small cell lung cancer (both non-squamous and squamous), without sensitizing EGFR, ALK, ROS1, BRAF and NTRK alterations, with chronic viral infections, such as HBV and HCV in cohort A. Squamous histology: carboplatin AUC 6 + paclitaxel 200 mg/m2 Non-squamous histology: carboplatin AUC 5 or 6 + pemetrexed 500 mg/m2 or cisplatin 75 mg/m2 + pemetrexed 500 mg/m2.

Drug: Nivolumab and Ipilimumab

Cohort B: HIV patients

EXPERIMENTAL

Participants (≥ 18 years) must have histologically confirmed metastatic or unresectable non-small cell lung cancer (both non-squamous and squamous), without sensitizing EGFR, ALK, ROS1, BRAF and NTRK alterations, with chronic viral infections such as HIV in cohort B. Squamous histology: carboplatin AUC 6 + paclitaxel 200 mg/m2 Non-squamous histology: carboplatin AUC 5 or 6 + pemetrexed 500 mg/m2 or cisplatin 75 mg/m2 + pemetrexed 500 mg/m2.

Drug: Nivolumab and Ipilimumab

Cohort C: Long COVID syndrome

EXPERIMENTAL

Participants (≥ 18 years) must have histologically confirmed metastatic or unresectable non-small cell lung cancer (both non-squamous and squamous), without sensitizing EGFR, ALK, ROS1, BRAF and NTRK alterations, with chronic viral infections such as Long Covid syndrome in Cohort C. Squamous histology: carboplatin AUC 6 + paclitaxel 200 mg/m2 Non-squamous histology: carboplatin AUC 5 or 6 + pemetrexed 500 mg/m2 or cisplatin 75 mg/m2 + pemetrexed 500 mg/m2.

Drug: Nivolumab and Ipilimumab

Interventions

Nivolumab and Ipilimumab DRUG

Nivolumab will be administered with ipilimumab, plus 2 cycles of histology-based platinum doublet chemotherapy: * Squamous histology: carboplatin AUC 6 + paclitaxel 200 mg/m2 * Non-squamous histology: carboplatin AUC 5 or 6 + pemetrexed 500 mg/m2 or cisplatin 75 mg/m2 + pemetrexed 500 mg/m Dosing: nivolumab 360 mg every 3 weeks + ipilimumab 1 mg/kg every 6 weeks (up to maximum 2 years) + histology-based, platinum doublet chemotherapy (every 3 weeks for two cycles).

Also known as: Opdivo and Yervoy

Cohort A: HBV and HCV patients; Cohort B: HIV patients; Cohort C: Long COVID syndrome

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed diagnosis of metastatic or unresectable NSCLC;
• No sensitizing EGFR, ALK, ROS1, BRAF and NTRK alterations;
• Eastern Cooperative Oncology Group (ECOG) score 0-1 (physically able to carry out light housework or office work through to being fully active as they were before cancer);
• No prior systemic anticancer therapy;
• Tissue or Programmed death-ligand 1 (PD-L1) results available;
• HIV-1 or HIV-2 chronic infection, defined as i) a positive HIV 1-2 western blot or other FDA/CE approved HIV confirmatory test (regardless the results of the HIV 1-2 screening test used \[2nd, 3rd, 4th generation tests, rapid tests or laboratory tests (i.e., ELISA, EIA, CLIA, etc.)\], ii) the referring physician's written record that HIV infection was documented, with supporting information on the participant's relevant medical history and/or current antiretroviral treatment for HIV infection;
• Only subjects with chronic or resolved HBV infections might be eligible. Chronic HBV infections is defined as: the persistence of HBsAg positivity for more than 6 months (regardless HBeAg result, HBV-DNA level and the presence of liver necroinflammation). Resolved HBV infection is defined by: the absence of liver inflammation (clinically and laboratory), HBsAg negativity and HBsAb (anti-HBs antibodies) and HBcAb (anti-HBc IgG) positive result;
• Only subjects with resolved HCV infections might be eligible. Subjects with a newly diagnosed chronic HCV infection (defined as: positive HCV antibodies + detectable HCV-RNA) should be treated for HCV infection before enrollment. Acute HCV infection \[defined as a positive HCV-RNA and i) a negative serological HCV assay (HCV-Ab) or ii) a positive serological HCV assay (HCV-Ab) with a negative test 6 months earlier\] cannot be enrolled in the study.
• Patients with past HCV infection, with no evidence of chronic infection (i.e., anti-HCV antibody positivity, HCV-RNA negativity) should be excluded;
• Patients with confirmed Long Covid syndrome or PASC defined, as suggest by World Health Organization (WHO), as "condition occurs in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms and that last for at least 2 months and cannot be explained by an alternative diagnosis". This condition must be present at enrollment;
• Participants must have a nasopharyngeal swab positive for Sars-Cov2 within 12 months before enrolment;
• Participants must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to first treatment;
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam; scans must have been performed within 4 weeks prior to registration.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug;
• Ability to understand and to sign a written informed consent document.

You may not qualify if:

• Eastern Cooperative Oncology Group (ECOG) score ≥2;
• Untreated symptomatic brain metastases or leptomeningeal metastases;
• Another active concomitant malignancy;
• Active, known or suspected, autoimmune disease;
• Active HBV or HCV infection, presence of any infectious disease requiring specific treatment.
• Active Sars-Cov2 infection.

Sponsors & Collaborators

• Universita di Verona: lead

Study Sites (1)

Centro Ricerche Cliniche

Verona, Veneto/Verona, 37134, Italy

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Post-Acute COVID-19 Syndrome

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Medical Oncologist

Model Details: Study type: Phase 2 - Interventional Trial Study drugs: nivolumab and ipilimumab Cohort A: HBV and HCV patients Cohort B: HIV patients Cohort C: Long COVID syndrome

Study Record Dates

• First Submitted: October 21, 2022
• First Posted: October 28, 2022
• Study Start: February 1, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 30, 2027
• Last Updated: October 28, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)