Trial Outcomes & Findings for A Study of Mobocertinib in Japanese Adults With Non-Small Cell Lung Cancer (NCT NCT03807778)

Participants took part in the study at 4 investigative sites for Phase 1 and 17 investigative sites for Phase 2 in Japan from 04 February 2019. The study is currently ongoing. Results in this summary are reported based on the primary completion date (08 November 2021) of the study.

Participants with a diagnosis of locally advanced or metastatic non-small cell lung cancer (NSCLC) were enrolled in a Dose Escalation Phase 1 Part of the study to receive mobocertinib (40, 120 or 160 milligram \[mg\]) and participants with locally advanced or metastatic NSCLC harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations were enrolled in Phase 2 Part of the study to receive RP2D of mobocertinib confirmed from the Phase 1 Part.

A Study of Mobocertinib in Japanese Adults With Non-Small Cell Lung Cancer

The RP2D was the maximum tolerated dose (MTD) or less. The MTD was declared when at least 9 participants were evaluable in the study and 6 participants were evaluable at the current dose, and the current dose was recommended for the next cohort. The dose recommended for use in phase 2 part was analyzed on the basis of the safety and tolerability data obtained in phase 1 part of the study.

Confirmed ORR is defined as percentage of participants who were confirmed to had achieved complete response (CR) or partial response (PR) per IRC using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 after the initiation of study treatment. Confirmed responses were responses that persisted on repeat imaging \>=4 weeks after initial response. CR (target lesion response): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 millimeter (mm) in short axis. CR (non-target lesion response): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level. PR (target lesions): at least 30% decrease in sum of the longest diameters (SLD) of target lesions, taking as reference baseline sum diameters. The SLD must also demonstrate an absolute increase of at least 5 mm.

DLT was defined as drug-related toxicity which met one of the following criteria and occurred within the first 28 days of study treatment (Cycle 1): Non-hematologic toxicities any \>=grade (G) 3 non-hematologic toxicity, with exception of self-limiting or medically controllable toxicities(nausea, vomiting, fatigue, electrolyte disturbances, hypersensitivity reactions) lasting \<3 days, excluding alopecia. Hematologic toxicities: febrile neutropenia not related to underlying disease (fever,\>38.3 degree Celsius \[C\]); absolute neutrophil count \<0.5\*10\^9 per liter \[/L\]); prolonged G4 neutropenia (\>=7 days) (if granulocyte-colony stimulating factor \[G-CSF\] required, event considered as DLT irrespective of the duration); neutropenic infection:\>=G3 neutropenia with \>=G3 infection; thrombocytopenia \>=G3 with bleeding, \>=G3 requiring platelet transfusion or G4 without bleeding lasting \>=7 days. Missed \>=25% of planned doses of drug over 28 days due to treatment-related AEs in first cycle.

DLT was defined as drug-related toxicity which met one of the following criteria and occurred within the first 28 days of study treatment (Cycle 1): Non-hematologic toxicities any \>=G 3 non-hematologic toxicity, with exception of self-limiting or medically controllable toxicities (nausea, vomiting, fatigue, electrolyte disturbances, hypersensitivity reactions) lasting \<3 days, excluding alopecia. Hematologic toxicities: febrile neutropenia not related to underlying disease (fever,\>38.3 degree C); absolute neutrophil count \<0.5\*10\^9/L); prolonged G4 neutropenia (\>=7 days) (if granulocyte-colony stimulating factor \[G-CSF\] required, event considered as DLT irrespective of the duration); neutropenic infection: \>=G3 neutropenia with \>=G3 infection; thrombocytopenia \>=G3 with bleeding, \>=G3 requiring platelet transfusion or G4 without bleeding lasting \>=7 days. Missed \>=25% of planned doses of drug over 28 days due to treatment-related AEs in first cycle.

The MTD was declared when at least 9 participants were evaluable in the study and 6 participants were evaluable at the current dose, and the current dose was recommended for the next cohort.

Rac (AUC 24) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (AUC 24) = AUC(0-24) on Cycle 2 Day 1/ AUC(0-24) on Cycle 1 Day 1.

Investigator assessed ORR using RECIST version 1.1 in participants with EGFR mutations. ORR was defined as the percentage of participants achieving CR and PR per RECIST version 1.1. Confirmed responses were responses that persisted on repeat imaging \>=4 weeks after initial response. CR (target lesion response): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis. CR (non-target lesion response): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level. PR (target lesions): at least 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. All participants with ORR had documentation of EGFR exon 20 insertion mutation.

Investigator assessed ORR using RECIST version 1.1 in participants with HER2 mutations. ORR was defined as the percentage of participants achieving CR and PR per RECIST version 1.1. Confirmed responses were responses that persisted on repeat imaging \>=4 weeks after initial response. CR (target lesion response): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis. CR (non-target lesion response): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level. PR (target lesions): at least 30% decrease in SLD of target lesions, taking as reference baseline sum diameters.

Confirmed ORR was defined as the percentage of the participants who were confirmed to have achieved CR or PR per the investigator using RECIST version 1.1. Confirmed responses were responses that persisted on repeat imaging \>=4 weeks after initial response. CR (target lesion response): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis. CR (non-target lesion response): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level. PR (target lesions): at least 30% decrease in SLD of target lesions, taking as reference baseline sum diameters.

Duration of response as assessed by the IRC was defined as the time interval from first documentation of CR/PR (whichever is first recorded) until the first date that PD is objectively documented. CR (target lesion response): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis. CR (non-target lesion response): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level; PR: At least a 30% decrease in SLD of target lesions, taking as a reference the baseline SLD. PD (target lesion response): SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest); PD (non-target lesion response): Unequivocal progression of existing non-target lesions. The SLD must also demonstrate an absolute increase of at least 5 mm.

Duration of response as assessed by the investigator was defined as the time interval from first documentation of CR/PR (whichever is first recorded) until the first date that PD is objectively documented. CR (target lesion response):disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis. CR (non-target lesion response): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level; PR: At least a 30% decrease in SLD of target lesions, taking as a reference the baseline SLD. PD (target lesion response): SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest); PD (non-target lesion response): Unequivocal progression of existing non-target lesions. The SLD must also demonstrate an absolute increase of at least 5 mm.

Time to response as assessed by the IRC was defined as the time interval from the date of the first dose of study treatment until the initial observation of CR or PR for participants with confirmed CR/PR. CR (target lesion response): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis. CR (non-target lesion response): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters.

Time to response as assessed by the investigator was defined as the time interval from the date of the first dose of study treatment until the initial observation of CR or PR for participants with confirmed CR/PR. CR (target lesion response): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis. CR (non-target lesion response): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level. PR: at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters.

DCR as assessed by IRC was defined as percentage of participants achieved CR, PR, stable disease (SD) (measurements must had met SD criteria at least once after study entry at minimum interval of 42 days) after initiation of study drug.CR(target lesion): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis.CR(non-target lesion): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level.PR(target lesions): at least 30% decrease in SLD of target lesions, taking as reference baseline sum diameters.SD(target lesion): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.PD(target lesion): SLD increased by at least 20% from smallest value on study, SLD must also demonstrate an absolute increase of at least 5 mm.PD (non-target lesion): unequivocal progression of existing non-target lesions.

DCR as assessed by investigator was defined as percentage of participants achieved CR, PR, SD (measurements must had met SD criteria at least once after study entry at minimum interval of 42 days) after initiation of study drug. CR (target lesion): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 mm in short axis. CR (non-target lesion): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level. PR (target lesions): at least 30% decrease in SLD of target lesions, taking as reference baseline sum diameters.SD (target lesion): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD(target lesion): SLD increased by at least 20% from smallest value on study, SLD must also demonstrate an absolute increase of at least 5 mm.PD (non-target lesion): unequivocal progression of existing non-target lesions.

PFS as assessed by the IRC was defined as the time interval from the start of study treatment until to the first documentation of PD or death due to any cause (whichever comes first) according to RECIST version 1.1.PD (target lesion response): SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest). The SLD must also demonstrate an absolute increase of at least 5 mm. PD (non-target lesion response): unequivocal progression of existing non-target lesions.

PFS as assessed by the investigator was defined as the time interval from the start of study treatment until to the first documentation of PD or death due to any cause (whichever comes first) according to RECIST version 1.1.PD (target lesion response): SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest). The SLD must also demonstrate an absolute increase of at least 5 mm. PD (non-target lesion response): unequivocal progression of existing non-target lesions.

OS was defined as the interval from the date of the first dose of the study treatment until death due to any cause.

EORTC QLQ-C30, version 3.0 was a cancer-specific questionnaire comprised of 5 functional scales (physical, role, cognitive, emotional, and social functioning); 3 symptom scales (fatigue, pain, and nausea/vomiting); a global health status (GHS)/quality-of-life (QoL) scale; and a six single-item scales (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). All other items have 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). Raw scores converted into scale scores ranging from 0 to 100. For functional and GHS/QoL scales, higher scores represent better HRQoL (positive change from Baseline=improvement), for symptom scales lower scores represent better QoL (i.e., a low level of symptomatology/problems) (negative change from Baseline=improvement), and for six-single item scale, lower scores represent better HRQoL (negative change from Baseline=improvement).

HRQOL scores was assessed with EORTC, it is a lung cancer module QLQ-LC13, version 3.0. QLQ-LC13 included 13 questions (4-point scale where 1=Not at all \[best\] to 4=Very much \[worst\]) assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain \[chest, arm or shoulder, other parts\]), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Subscale score range: 0 to 100. Higher symptom score = greater degree of symptom severity.