Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Paclitaxel

Carboplatin

Pemetrexed

Albumin-Bound Paclitaxel

Immunomodulating Agents

Nivolumab

Ipilimumab

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Arm A - Intervention arm (Immunotherapy and Chemotherapy)

Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks

Platinum- doublet Chemotherapy (Histology-based) 4 cycles depending on the investigator's discretion.

Carboplatin dosed at AUC 5, and either Paclitaxel 175 mg/m2 for squamous or Pemetrexed 500 mg/m2 for non-squamous

Arm B - control arm (Immunotherapy only)

Nivolumab 360 mg/kg every 3 weeks Ipilimumab 1 mg/kg every 6 weeks

Lauren Finaldi

Suzanne Kosky

Walter Elliot

Martin Gutierrez, MD

This clinical trial plans to assess to what extent the on-treatment circulating tumor DNA (ctDNA) can predict the subset of patients with NSCLC who will respond to immunotherapy treatment only and which patients will need both immunotherapy and chemotherapy modalities for their treatment regimen.

Subjects will be randomized 2:1 and patients in both arms will begin treatment with nivolumab 360 mg intravenously every 3 weeks and ipilimumab 1 mg/kg intravenously every 6 weeks. At five weeks of treatment, subjects will have ctDNA response evaluation with Guardant360 Response assay. At the next cycle of treatment (+/- 2 days), patients in the larger arm will receive treatment based on the Guardant360 Response assay results, as described below. Subjects will undergo ctDNA evaluation with Guardant360 Response assay 6- week post-randomization and at the time of progression. Response to therapy will be assessed by interval imaging with CT scan of the chest/abdomen/pelvis (and MRI brain if applicable) with response evaluated by irRECIST criteria every 12 weeks until disease progression.

Subjects will be randomized 2:1 and patients in both arms will begin treatment with nivolumab 360 mg intravenously every 3 weeks and ipilimumab 1 mg/kg intravenously every 6 weeks. At five weeks of treatment, subjects will have ctDNA response evaluation with Guardant360 Response assay. At the next cycle of treatment (+/- 2 days), patients in the arm A will receive treatment based on the Guardant360 Response assay results, as described below. Arm B will continue the immunotherapy only.

Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy

A Multicenter Phase II Randomized Trial Of Immunotherapy Versus Chemotherapy Guided By Circulating Tumor DNA-Based Molecular Response On Patients With Metastatic NSCLC

To compare progression free survival in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results.

To compare progression free survival on subsequent line of therapy (PFS2) between patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results

To compare overall survival (OS) in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results

To compare objective response rate (ORR) in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on treatment-ctDNA results.

To compare duration of response (DOR) in patients with on-treatment-ctDNA guided therapy continuation or escalation by addition of platinum-doublet chemotherapy to therapy continuation with Nivolumab-Ipilimumab regardless of on-treatment-ctDNA results.

Serious adverse events will be summarized by treatment group as number and percentages. Overall summary of SAEs by grade (any grade, grade 3-4, grade 5) will be reported. Overall summary of drug-related SAEs by worst CTC grade (any grade, grade 3-4, grade 5) will be reported.

MedSIR

Hackensack Meridian Health

Symptoms and General Pathology

Rare Diseases

Adenocarcinoma

Neoplasm Metastasis

Adenocarcinoma of Lung

Lung Adenocarcinoma

Docetaxel

Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the investigational drug arm.

AUY922 was to be administered weekly.

Participants were assigned to one of two treatment arms in a ratio of 1:1. This was the control arm drug arm.

Pemetrexed or docetaxel was to be was to be given once every three weeks.

AUY922 was to be given by i.v. once weekly at 70 mg/m2 until disease progression, death or any other reason for discontinuation from study treatment.

AUY922

Docetaxel was to be given i.v. once every 3 weeks at 75 mg/m2 until progression or unacceptable toxicity

Pemetrexed was to be given once every 3 weeks at 500 mg/m2 until progression or unacceptable toxicity

Novartis Pharmaceuticals

The purpose of this study was to determine if AUY922 had superior efficacy when compared to chemotherapy agents docetaxel or pemetrexed in patients whose tumor had EGFR mutations.

The primary purpose of this study was to compare the efficacy of AUY922, when administered i.v. on a once-weekly schedule at 70 mg/m2, versus docetaxel or pemetrexed in adult patients with advanced NSCLC, whose tumors harbored EGFR activating mutations, and had developed resistance to EGFR TKI.

An Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations

A Multicenter, Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations Who Have Progressed on Prior EGFR TKI Treatment

Compared PFS between the treatment of AUY922 to comparators Pemetrexed or Docetaxel. Progression-free survival (PFS) based on local investigator assessment per RECIST 1.1 was the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

ORR was to be compared between treatment arms. The ORR was to be based on local investigator assessment per Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1). Per this criteria for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.This outcome measure was originally planned to be analyzed up to 24 months. The DMC recommendation at the IA was to stop the study for futility. As a result, collection of all the efficacy assessments was stopped at that time.

OS is defined as the time from the date of randomization to date of death due to any cause. If a death has not been observed by the date of analysis cutoff, then OS was to be censored at the last known date patient was alive.

Duration of DCR will be compared between treatment arms. The duration of DCR will be based on local investigator assessment per RECIST 1.1

TTR was to compare between treatment arms. The TTR was to be based on local investigator assessment per RECIST 1.1

The DOR will be compared between treatment arms. The DOR will be based on local investigator assessment per RECIST 1.1

To evaluate safety and tolerability of AUY922 compared to chemotherapy agents pemetrexed or docetaxel.

Changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), Dose interruptions, reductions and dose intensity.

TTP will be compared between treatment arms. The TTP will be based on local investigator assessment per RECIST 1.1

Safety set: comprised of all participants who received at least one dose of study medication (AUY922, pemetrexed or docetaxel). In the safety set, patients were classified and analyzed according to the treatment received. Of the 59 participants randomized, only 52 received one dose of study medication.

AUY922 Arm

Chemotherapy Arm

Total

Age, Continuous

Sex: Female, Male

Full analysis set (FAS) comprised of all patients who were randomized to a study treatment.

The data monitoring committee (DMC's) recommendation based on the Interim Analysis (IA) results to terminate the study early due to futility, data was not collected for this assessment on many of the secondary endpoints.

Study Director

Efficacy analysis set (EAS) compromised of a subset of patients in the FAS who received 2 lines of prior antineoplastic therapy consisting of a platinum-based treatment \& an EGFR TKI treatment. The DMC recommendation at Interim analysis was to stop the study for futility. As a result, collection of all efficacy assessments was stopped.

Progression Free Survival (PFS)

Complete Response (CR)

Partial Response (PR)

ORR (CR + PR)

The data monitoring committee's (DMC's) recommendation based on the Interim Analysis (IA) results was to terminate the study early due to futility; collection of efficacy data for assessment was stopped at that time.

Overall Response Rate (ORR)

The data monitoring committee (DMC's) recommendation based on the Interim Analysis (IA) results was to terminate the study early due to futility; collection of efficacy data for assessment was stopped at that time.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy	NCT05715229	Carcinoma, Non-...	Nivolumab Ipilimumab Carboplatin Paclitaxel Pemetrexed	18 Years -	Hackensack Meridian Health
Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy	NCT05715229	Carcinoma, Non-...	Nivolumab Ipilimumab Carboplatin Paclitaxel Pemetrexed	18 Years -	Hackensack Meridian Health
Immune Profile Selection By Fraction of ctDNA in Patients With Advanced NSCLC Treated With Immunotherapy	NCT05715229	Carcinoma, Non-...	Nivolumab Ipilimumab Carboplatin Paclitaxel Pemetrexed	18 Years -	Hackensack Meridian Health
An Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations	NCT01646125	Advanced Non Sm...	AUY922 Docetaxel Pemetrexed	18 Years -	Novartis
An Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations	NCT01646125	Advanced Non Sm...	AUY922 Docetaxel Pemetrexed	18 Years -	Novartis

Spots Global Cancer Trial Database for advanced non small cell lung cancer (nsclc)