Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Amino Acids

Pembrolizumab

Afatinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

pembrolizumab

The main objective is to assess the efficacy of afatinib in combination with pembrolizumab, as measured by objective response (OR) in patients with locally advanced or metastatic squamous NSCLC who progressed during or after first line platinum-based treatment.

The secondary objectives are to confirm the RP2D, assess the safety profile, and the secondary measures of clinical efficacy including disease control (DC), duration of objective response (DoR), progression-free survival (PFS), overall survival (OS), and tumour shrinkage.

Testing Afatinib in Combination With Pembrolizumab in Patients With Squamous Cell Carcinoma of the Lung

LUX-Lung IO: A Phase II, Open Label, Non-randomised Study of Afatinib in Combination With Pembrolizumab in Patients With Locally Advanced or Metastatic Squamous Cell Carcinoma of the Lung

Objective response rate is defined as percentage of participants with the best overall response of complete response (CR, disappearance of all target lesions) or confirmed partial response (PR, at least a 30% decrease in sum of diameter (SoD, longest diameter (LD) measured for all lesions except lymph nodes, where shortest diameter (ShD) was used) of target lesions, reference is baseline SoD). Tumour response was assessed based on local radiological image (Computerised tomography (CT) or Magnetic resonance imaging (MRI)) evaluation by the investigators according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1.

Recommended Phase II Dose (RP2D) was to be calculated through a Bayesian logistic regression model (BLRM) with overdose control that was to be fitted to binary toxicity outcomes. After 12 patients had completed at least one cycle (one cycle equals 21 days and consists of one time infusion of pembrolizumab at Day 1 + daily intake of afatinib) of treatment, the prior distributions were to be updated through Gibbs sampling procedures with the accumulated dose limiting toxicity (DLT) data from the first treatment cycle. The estimate of parameters was to be updated as data were accumulated using the BLRM. At the end of the dose confirmation, the toxicity probability at each dose level was to be calculated to determine an estimate of the RP2D. Posterior probabilities for the rate of DLT were to be summarised from BLRM. Confirmation of the RP2D by the Safety Monitoring Committee (SMC) was to be based on these probabilities as well as on the review of other safety and laboratory data.

Disease control rate was calculated as percentage of participants with CR, PR, or stable disease (SD, neither sufficient shrinkage to qualify for PR, taking as reference the baseline sum of diameters (SoD), nor sufficient increase to qualify for progressive disease (PD, at least a 20% increase in the SoD of target lesions, taking as reference the smallest SoD recorded on study (including baseline), together with an absolute increase in the SoD of at least 5 millimeter (mm ) or the appearance of one or more new lesions). Tumour response was assessed based on local radiological image (Computerised tomography (CT) or Magnetic resonance imaging (MRI)) evaluation by the investigators according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1.

For participants who showed objective response, duration of objective response (DoR), was defined as the time from first documented complete response (CR) or partial response (PR) until the earliest of disease progression (PD) or death. Tumour response was assessed based on local radiological image (CT or MRI) evaluation by the investigators according to RECIST version 1.1. The number of participants with objective response who experienced the event "disease progression or death (whichever came first)" is reported instead of a metric summarizing the time-to-event data with unit of time, as the number analyzed was too small to perform a Kaplan-Meier-analysis.

Progression-free survival was defined as the time (weeks) from the date of the first afatinib or pembrolizumab administration to the date of disease progression (at least a 20% increase in the sum of diameter (SoD, longest diameter (LD) measured for all lesions except lymph nodes, where shortest diameter (ShD) was used) of target lesions, taking as reference the smallest SoD recorded on study (including baseline), together with an absolute increase in the SoD of at least 5 mm or the appearance of one or more new lesions) or death (if the patient died without progression). The date of progression for the primary analyses was determined based on investigator assessment. Tumour response was assessed based on local radiological image (Computerised tomography (CT) or Magnetic resonance imaging (MRI)) evaluation by the investigators according to RECIST version 1.1. Median and 95% Confidence Interval were calculated using Kaplan-Meier estimates.

Overall survival is defined as the time from the date of treatment start to the date of death from any cause. Participants without event were censored. Median and 95% Confidence Interval were calculated using Kaplan-Meier estimates.

Tumour shrinkage (in millimeters) is defined as the difference between the minimum post-baseline sum of diameters of target lesions (SoD, longest for non-nodal lesions, short axis for nodal lesions) and the baseline sum of diameters of the same set of target lesions. Tumour shrinkage is reported as percentage change from baseline and represents the maximum decrease or the minimum increase from baseline in SoD in percentage of the baseline SoD. Negative values indicate a reduction in the SoD; positive values indicate an increase in the SoD. Tumour response was assessed based on local radiological image (CT or MRI) evaluation by the investigators according to RECIST 1.1.

Boehringer Ingelheim

The treated set (TS) included all participants, who received at least one dose of afatinib or pembrolizumab.

40 milligram (mg) of afatinib film-coated tablet, given orally with a glass of water (without food consumption 3 hours (h) prior and 1h post afatinib administration), once daily + pembrolizumab 200 mg, intravenous infusion, once every 3 weeks.

Both afatinib and pembrolizumab were to be given until documented disease progression, or unacceptable adverse events, or other reasons requiring treatment discontinuation, or for up to 35 cycles of 21 days (i.e. the approved pembrolizumab monotherapy duration). In case of early discontinuation of one agent, the other agent could be continued as monotherapy for altogether up to 35 cycles.

Afatinib 40 mg + Pembrolizumab 200 mg

30 mg of afatinib film-coated tablet, given orally with a glass of water (without food consumption 3 hours (h) prior and 1h post afatinib administration), once daily + pembrolizumab 200 mg, intravenous infusion, once every 3 weeks.

Both afatinib and pembrolizumab were to be given until documented disease progression, or unacceptable adverse events, or other reasons requiring treatment discontinuation, or for up to 35 cycles of 21 days (i.e. the approved pembrolizumab monotherapy duration). In case of early discontinuation of one agent, the other agent could be continued as monotherapy for altogether up to 35 cycles.

Afatinib 30 mg + Pembrolizumab 200 mg

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

After the safety run-in, the SMC decided that the benefit-risk ratio was not favorable and recommended ending the trial according to a protocol-defined option. Trial was completed as described in protocol.

Boehringer Ingelheim, Call Center

Objective Response Rate (ORR)

Comprises both arms during the safety run-in part. 30 or 40 milligram (mg) of afatinib film-coated tablet, given orally with a glass of water (without food consumption 3 hours (h) prior and 1h post afatinib administration), once daily + pembrolizumab 200 mg, intravenous infusion, once every 3 weeks.

Both afatinib and pembrolizumab were to be given until documented disease progression, or unacceptable adverse events, or other reasons requiring treatment discontinuation, or for up to 35 cycles of 21 days (i.e. the approved pembrolizumab monotherapy duration). In case of early discontinuation of one agent, the other agent could be continued as monotherapy for altogether up to 35 cycles.

Afatinib + Pembrolizumab

The treated set (TS) included all participants, who received at least one dose of afatinib or pembrolizumab. Because the Safety Monitoring Committee (SMC) decided that the benefit-risk ratio of afatinib in combination with pembrolizumab was not favorable, the trial was stopped according to a protocol-defined option and the decision on RP2D was not performed.

Recommended Phase II Dose (RP2D)

The treated set (TS) included all participants who received at least one dose of afatinib or pembrolizumab.

Disease Control Rate (DCR)

All participants who received at least one dose of afatinib or pembrolizumab and showed objective response.

Spots Global Cancer Trial Database for Testing Afatinib in Combination With Pembrolizumab in Patients With Squamous Cell Carcinoma of the Lung

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