A Value-Driven Study on Reducing Immune Checkpoint Inhibitor Dosing Frequency in Advanced Cancers

NCT ID: NCT06422403

Last Updated: 2025-01-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-25
• Study Completion Date: 2029-12-31

Brief Summary

This study is a prospective, open label, multi-centre phase 2 trial which assesses the efficacy and safety of standard dosing compared to extended dosing interval of nivolumab, atezolizumab or pembrolizumab in advanced/unresectable gastric/gastroesophageal junction/oesphageal adenocarcinomas with PDL1 CPS ≥5%, hepatocellular carcinoma andnon-small cell lung cancer with PDL1 TPS≥50% with no prior treatment. The investigators hypothesize that nivolumab, pembrolizumab and atezolizumab can be used efficiently at extended dosing intervals, compared to their approved labels with comparable clinical outcome.

Detailed Description

This study aims to assess the noninferiority of progression free survival of standard dosing compared to extended dosing interval of nivolumab, pembrolizumab and atezolizumab in advanced/unresectable gastric/gastroesophageal junction/oesphageal adenocarcinomas with PDL1 CPS ≥5%, hepatocellular carcinoma, and non-small cell lung cancer with PDL1 TPS≥50%.

Secondary Objective

• To investigate the safety, overall survival (OS) of ICI at extended dosing interval of the standard versus extended dosing interval groups.
• To investigate the pharmacokinetics (PK) of nivolumab, atezolizumab or pembrolizumab.

Conditions

Carcinoma, Hepatocellular; Gastric Adenocarcinoma; GastroEsophageal Cancer; Oesophageal Cancer; Non-small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A (SOC)

Nivolumab, XELOX/FOLFOX

Group Type: ACTIVE_COMPARATOR

Standard of Care - A

Intervention Type: DRUG

Nivolumab 360mg 3 weekly (up to 2 years) + XELOX Nivolumab 240mg 2 weekly (up to 2 years) + FOLFOX

Cohort A (EDI)

Nivolumab, XELOX/FOLFOX

Group Type: EXPERIMENTAL

Extended Dosing Interval - A

Intervention Type: DRUG

Nivolumab 360mg 6 weekly (up to 2 years) + XELOX Nivolumab 240mg 4 weekly (up to 2 years) + FOLFOX

Cohort B (SOC)

Bevacizumab, Atezolizumab

Group Type: ACTIVE_COMPARATOR

Standard of Care - B

Intervention Type: DRUG

Bevacizumab + Atezolizumab 1200mg 3 weekly (up to 2 years)

Cohort B (EDI)

Bevacizumab, Atezolizumab

Group Type: EXPERIMENTAL

Extended Dosing Interval - B

Intervention Type: DRUG

Bevacizumab + Atezolizumab 1200mg 6 weekly (up to 2 years)

Cohort C (SOC)

Pembrolizumab

Group Type: ACTIVE_COMPARATOR

Standard of Care - C

Intervention Type: DRUG

Pembrolizumab 200mg 3 weekly (up to 2 years)

Cohort C (EDI)

Pembrolizumab

Group Type: EXPERIMENTAL

Extended Dosing Interval - C

Intervention Type: DRUG

Pembrolizumab 200mg 6 weekly (up to 2 years)

Interventions

Extended Dosing Interval - A

Nivolumab 360mg 6 weekly (up to 2 years) + XELOX Nivolumab 240mg 4 weekly (up to 2 years) + FOLFOX

Intervention Type: DRUG

Extended Dosing Interval - B

Bevacizumab + Atezolizumab 1200mg 6 weekly (up to 2 years)

Intervention Type: DRUG

Extended Dosing Interval - C

Pembrolizumab 200mg 6 weekly (up to 2 years)

Intervention Type: DRUG

Standard of Care - A

Nivolumab 360mg 3 weekly (up to 2 years) + XELOX Nivolumab 240mg 2 weekly (up to 2 years) + FOLFOX

Intervention Type: DRUG

Standard of Care - B

Bevacizumab + Atezolizumab 1200mg 3 weekly (up to 2 years)

Intervention Type: DRUG

Standard of Care - C

Pembrolizumab 200mg 3 weekly (up to 2 years)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Provision of informed consent prior to any study-specific procedure

2. Patients with one of the following:

• Cohort A: Previously untreated locally advanced/metastatic HER2 -ve gastric/gastroesophageal junction/esophageal (PDL1 CPS ≥5% adenocarcinomas not amenable to curative surgery or radiotherapy who are above to begin platinum double and nivolumab.
• Cohort B: Previously untreated locally advanced/metastatic Child's A hepatocellular carcinoma not amenable to curative surgery or radiotherapy who are above to begin atezolizumab and bevacizumab.
• Cohort C: Previously untreated locally advanced/metastatic lung adenocarcinoma (PDL1 TPS≥50%, EGFR/ALK wildtype) not amenable to curative surgery or radiotherapy who are above to begin pembrolizumab monotherapy

3. Measurable disease per RECIST 1.1 criteria

4. ECOG Performance status is 0-2

5. Normal organ and bone marrow function measured within 28 days before the study as defined below:

• Haemoglobin ≥ 8.0 g/dL and no blood transfusions in the 28 days prior to entry
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• No features suggestive of MDS/AML on peripheral blood smear
• White blood cells (WBC) > 3x10^9/L
• Platelet count ≥ 100 x 10^9/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
• Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)

6. A life expectancy ≥ 12 weeks in all patients.

7. Females in childbearing age should be using adequate contraceptive measures, should not be breastfeeding and their pregnancy test prior to the start of treatment must be negative. Evidence of non-child-bearing potential is fulfilled by one of the following criteria at screening:

8. The post-menopausal period defined as age ≥50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments

9. Women <50 years old they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range.

10. Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not a tubal ligatio

11. Male patients should be willing to use barrier contraception

12. The patient is willing to comply with the protocol during the study including undergoing treatment and scheduled visits and examinations including follow up.

13. At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and is considered suitable for accurate repeated measurements

Exclusion Criteria

1. Patients who have previously received immune checkpoint inhibitors or investigational monoclonal antibody therapy.

2. Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years

3. Unstable spinal cord compression/brain metastases unless asymptomatic and not requiring steroids for at least 2 weeks prior to the start of study treatment. For patients with brain metastases, gamma knife or stereotactic brain surgery is allowed prior to study treatment.

4. Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. Minor surgery is allowed.

5. Severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which based on investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or having active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.

6. Autoimmune disorders

7. Males and females of reproductive potential who are not using an effective method of contraception and females who are pregnant or breastfeeding or have a positive serum pregnancy test prior to study entry

8. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

9. Previous allogeneic bone marrow transplant.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National University Hospital, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wei Peng Yong

Role: PRINCIPAL_INVESTIGATOR

National University Hospital, Singapore

Locations

Department of Hematology-Oncology, National University Hospita

Singapore, , Singapore

Site Status: RECRUITING

Countries

Singapore

Central Contacts

Wei Peng Yong

Role: CONTACT

Wei_Peng_YONG@nuhs.edu.sg

+65 6908 2222

Facility Contacts

Wei Peng Yong

Role: primary

Wei_Peng_YONG@nuhs.edu.sg

+65 6908 2222

Other Identifiers

2024-3881

Identifier Type: -

Identifier Source: org_study_id