Non-Small Cell Lung Cancer
Conditions
Brief summary
This study is in 2 parts. Different participants will take part in the 1st and 2nd parts of the study. The main aim of the 1st part of the study is to check how much Mobocertinib adults with non-small cell lung cancer (NSCLC) can receive without getting side effects from it. The main aim of the 2nd part of the study is to learn if the condition of adults with non-small cell lung cancer improves after treatment with Mobocertinib. Another aim is to continue checking for side effects from Mobocertinib. In the 1st part of the study, at the first visit, the study doctor will check who can take part. For those that can take part, participants will take a capsule of Mobocertinib once a day for 28 days. This will count as 1 cycle. Different small groups of participants will receive lower to higher doses of Mobocertinib. The study doctors will check for side effects after each dose of TAK 788. In this way, researchers can work out the best dose of Mobocertinib to give participants in the 2nd part of the study. Participants will visit the clinic 30 days after their treatment has finished for a final check-up. In the 2nd part of the study, at the first visit, the study doctor will check who can take part. Participants will receive the best dose of Mobocertinib worked out from the 1st part of the study. Participants will receive Mobocertinib in the same way as those from the 1st part of the study. The study doctors will learn if the condition of these participants improves after treatment with Mobocertinib. The study doctors will also check for side effects from Mobocertinib. After treatment has finished, participants will visit the clinic every 12 weeks until the end of the study. In both parts of the study, participants can receive Mobocertinib for up to just over 1 year, or longer if their condition stays improved.
Detailed description
The drug being tested in this study is called Mobocertinib. Mobocertinib is being tested to treat Japanese participants with NSCLC. This study has two parts (Phase 1 part and Phase 2 part), Phase 1 part of this study will look at the safety, efficacy, tolerability and PK of Mobocertinib orally administered once daily, and will determine a RP2D. Phase 2 study will look at the efficacy and safety of Mobocertinib in treatment naive Japanese NSCLC patients with epidermal growth factor receptor (EGFR) exon 20 insertion mutation. All participants will be assigned to Phase 1 part or Phase 2 part and will be asked to take Mobocertinib capsule as following dosage and regimen; Phase 1 part; Mobocertinib, 40 mg as starting dose, once daily, and escalating up to 160 mg until a Maximum Tolerated Dose (MTD). An expansion phase may be followed at any dose to further confirm safety observations following identification of MTD/RP2D. Phase 2 part; Mobocertinib, 160 mg, once daily The study will enroll approximately 58-63 participants (Phase 1 part; 28-33 and Phase 2 part; 30). This multi-center trial will be conducted in Japan. The overall time to participate in this study of Phase 1 part is approximately 3 years and Phase 2 part is approximately 4 years. Participants will make multiple visits to the clinic in the treatment period, and the post-treatment period including follow-up assessments after the last dose of the study drug.
Interventions
DRUGMobocertinib
Mobocertinib capsule.
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria (Both in Phase 1 and Phase 2 Part); 1. Male or female patients ≥20 years old. 2. Must have measurable disease by RECIST v1.1. Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy. 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. 4. Minimum life expectancy of 3 months or more. 5. Adequate renal and hepatic function as defined by the following criteria: •Total serum bilirubin ≤1.5 × upper limit of normal (ULN) (≤3.0 × ULN for patients with Gilbert syndrome or if liver function abnormalities are due to underlying malignancy); •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN (or ≤5 × ULN if liver function abnormalities are due to underlying malignancy); •Estimated creatinine clearance ≥30 mL/min (calculated by using the Cockcroft-Gault equation); •Serum albumin ≥2 g/dL; and •Serum lipase ≤1.5 × ULN; and •Serum amylase ≤1.5 × ULN unless the increased serum amylase is due to salivary isoenzymes. 6. Adequate bone marrow function as defined by the following criteria: * Absolute neutrophil count ≥1.5 × 109/L; * Platelet count ≥75 × 109/L in Phase 1 Part and ≥100 × 109/L in Phase 2 Part; and * Hemoglobin ≥9.0 g/dL. 7. Normal QT interval on screening ECG, defined as QTcF of ≤450 ms in males or ≤470 ms in females. 8. Female patients who: * Are postmenopausal (natural amenorrhea and not due to other medical reasons) for at least 1 year before the screening visit, OR * Are surgically sterile, OR * If they are of childbearing potential, agree to practice 1 highly effective non-hormonal method of contraception and 1 additional effective (barrier) method (see Section 8.7.1) at the same time, from the time of signing the informed consent form (ICF) through 30 days after the last dose of study drug, OR * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. Note: Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Male patients, even if surgically sterilized (ie, status postvasectomy), who: * Agree to practice effective barrier contraception during the entire study treatment period and through 30 days after the last dose of study drug, OR * Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. Note: Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. 9.Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care. 10.Willingness and ability to comply with scheduled visits and study procedures. * Phase-Specific Inclusion Criteria (Phase 1 part); 1.Have histologically or cytologically confirmed locally advanced (and not a candidate for definitive therapy) (Stage IIIB) or metastatic NSCLC (Stage IV). 2.Refractory to standard available therapies. 3.All toxicities from prior therapy have resolved to ≤ grade 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0), or have resolved to baseline, at the time of first dose of Mobocertinib. Note: treatment-related grade \>1 alopecia or treatment-related grade 2 peripheral neuropathy are allowed if deemed irreversible. * Phase-Specific Inclusion Criteria (Phase 2 part); 1. Histologically or cytologically confirmed locally advanced not suitable for definitive therapy, recurrent, or metastatic (Stage IV) NSCLC. 2. Not received prior systemic treatment for locally advanced or metastatic disease (with the exception below): Neoadjuvant or adjuvant chemotherapy/immunotherapy for Stage I to III or combined modality chemotherapy/radiation for locally advanced disease is allowed if completed \>6 months before the development of metastatic disease. 3. A documented EGFR in-frame exon 20 insertion (including A763\_Y764insFQEA, V769\_D770insASV, D770\_N771insNPG, D770\_N771insSVD, H773\_V774insNPH, or any other in-frame exon 20 insertion mutation) by a local test that has been analytically validated per local authority guidelines. The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or HER2 mutations except EGFR common mutations (exon 19 del or L858R). 4. Adequate tumor tissue available, either from primary or metastatic sites, for central laboratory confirmation of EGFR in-frame exon 20 insertion mutation. Note: confirmation of central test positivity is not required before the first dose of Mobocertinib.
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 Part: Recommended Phase 2 Dose (RP2D) of Orally Administered Mobocertinib | Cycle 1 (Cycle length=28 days) | 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. |
| Phase 2 Part: Confirmed Objective Response Rate (ORR) as Assessed by the Independent Review Committee (IRC) | From the first dose of the study drug until progressive disease (PD) (up to 2 years and 9 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 Part, Tmax: Time of First Occurrence of Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Cycle 1 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days) | — |
| Phase 1 Part, AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Cycle 1 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days) | — |
| Phase 1 Part, Cmax, ss: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Cycle 2 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days) | — |
| Phase 1 Part, Tmax, ss: Time of First Occurrence of Cmax for Mobocertinib Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Cycle 2 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days) | — |
| Phase 1 Part, AUC24, ss: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Cycle 2 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days) | — |
| Phase 1 Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | From first dose of study drug until 30 days after the last dose or before initiation of new anticancer therapy (whichever comes first) (Up to 2 years and 9 months, till data cut-off of 08 November 2021) | — |
| Phase 1 Part: Number of Participants With First Cycle DLTs Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.00 | Cycle 1 (Cycle length=28 days) | 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. |
| Phase 1 Part: Number of DLTs for Mobocertinib Based on NCI CTCAE, Version 5.00 | Cycle 1 (Cycle length=28 days) | 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. |
| Phase 1 Part: Maximum Tolerated Dose (MTD) of Orally Administered Mobocertinib | Cycle 1 (Cycle length=28 days) | 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. |
| Phase 1 Part: ORR in Participants With EGFR Mutations as Assessed by Investigator | From the first dose of the study drug until PD (up to 2 years and 9 months, till data cut-off of 08 November 2021) | 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. |
| Phase 1 Part: ORR in Participants With HER2 Mutations as Assessed by Investigator | From the first dose of the study drug until PD (up to 2 years and 9 months, till data cut-off of 08 November 2021) | 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. |
| Phase 2 Part: Confirmed ORR as Assessed by the Investigator | From the first dose of the study drug until PD (up to 2 years and 9 months, till data cut-off of 08 November 2021) | 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. |
| Phase 2 Part: Duration of Response (DOR) as Assessed by the IRC as Per RECIST V1.1 | From first documentation of CR/PR until first PD (Up to 2 years and 9 months, till data cut-off of 08 November 2021) | 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. |
| Phase 2 Part: DOR as Assessed by Investigator as Per RECIST V1.1 | From first documentation of CR/PR until first PD (Up to 2 years and 9 months, till data cut-off of 08 November 2021) | 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. |
| Phase 2 Part: Time to Response as Assessed by the IRC as Per RECIST V1.1 | From the first dose of the study drug up to first confirmed CR or PR (Up to 2 years 9 months, till data cut-off of 08 November 2021) | 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. |
| Phase 2 Part: Time to Response as Assessed by the Investigator Per RECIST V1.1 | From the first dose of the study drug up to first confirmed CR or PR (Up to 2 years 9 months, till data cut-off of 08 November 2021) | 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. |
| Phase 2 Part: Disease Control Rate (DCR) as Assessed by the IRC as Per RECIST V1.1 | From the first dose of the study drug until PD (Up to 2 years 9 month, till data cut-off of 08 November 2021) | 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. |
| Phase 2 Part: DCR as Assessed by the Investigator Per RECIST V1.1 | From the first dose of the study drug until PD (Up to 2 years 9 month, till data cut-off of 08 November 2021) | 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. |
| Phase 2 Part: Progression Free Survival (PFS) as Assessed by the IRC as Per RECIST V1.1 | From the first dose of the study drug until PD or death due to any cause (whichever comes first) (Up to 2 years and 9 months, till data cut-off of 08 November 2021 | 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. |
| Phase 2 Part: PFS as Assessed by the Investigator as Per RECIST V1.1 | From the first dose of the study drug until PD or death due to any cause (whichever comes first) (Up to 2 years and 9 months, till data cut-off of 08 November 2021 | 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. |
| Phase 2 Part: Overall Survival (OS) | From the start of the study drug up to death due to any cause (Up to 2 years 9 months, till data cut-off of 08 November 2021) | OS was defined as the interval from the date of the first dose of the study treatment until death due to any cause. |
| Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Baseline and at 30 days after last dose (at Month 19) | 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). |
| Phase 1 Part, Rac (AUC 24): Extent of Accumulation Ratio Based on AUC 24 on Multiple Dosing for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Cycle 2 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days) | 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. |
| Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Baseline and at 30 days after last dose (at Month 19) | 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. |
| Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Cycle 1 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days) | — |
Countries
Japan
Contacts
STUDY_DIRECTORStudy Director
Takeda
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Mobocertinib 40 mg, Phase 1 Part Mobocertinib 40 mg (as the starting dose), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle until disease progression or intolerable toxicity, or another discontinuation criterion in participants with locally advanced or metastatic NSCLC. | 4 |
| Mobocertinib 120 mg, Phase 1 Part Mobocertinib 120 mg, capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle until disease progression or intolerable toxicity, or another discontinuation criterion in participants with locally advanced or metastatic NSCLC. | 4 |
| Mobocertinib 160 mg, Phase 1 Part Mobocertinib 160 mg, capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle until disease progression or intolerable toxicity, or another discontinuation criterion in participants with locally advanced or metastatic NSCLC. | 12 |
| Mobocertinib 160 mg, Phase 2 Part Mobocertinib 160 mg, capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle until disease progression or intolerable toxicity, or another discontinuation criterion in participants with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations. | 33 |
| Total | 53 |
Baseline characteristics
| Characteristic | Mobocertinib 120 mg, Phase 1 Part | Mobocertinib 40 mg, Phase 1 Part | Total | Mobocertinib 160 mg, Phase 2 Part | Mobocertinib 160 mg, Phase 1 Part |
|---|---|---|---|---|---|
| Age, Customized >=65 to <75 years | 2 Participants | 2 Participants | 20 Participants | 11 Participants | 5 Participants |
| Age, Customized >=75 years | 0 Participants | 0 Participants | 7 Participants | 6 Participants | 1 Participants |
| Age, Customized Greater than or equal to (>=) 50 to < 65 years | 1 Participants | 1 Participants | 18 Participants | 12 Participants | 4 Participants |
| Age, Customized Less than (<) 50 | 1 Participants | 1 Participants | 8 Participants | 4 Participants | 2 Participants |
| Central Nervous System (CNS) involvement at Screening Was involved | 4 Participants | 2 Participants | 26 Participants | 16 Participants | 4 Participants |
| Central Nervous System (CNS) involvement at Screening Was not involved | 0 Participants | 2 Participants | 27 Participants | 17 Participants | 8 Participants |
| Disease Stage at Screening IIIB | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Disease Stage at Screening IV | 4 Participants | 4 Participants | 19 Participants | 0 Participants | 11 Participants |
| Disease Stage at Screening IVA | 0 Participants | 0 Participants | 16 Participants | 16 Participants | 0 Participants |
| Disease Stage at Screening IVB | 0 Participants | 0 Participants | 15 Participants | 15 Participants | 0 Participants |
| Disease Stage at Screening Other | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 | 0 Participants | 2 Participants | 28 Participants | 21 Participants | 5 Participants |
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) 1 | 4 Participants | 2 Participants | 25 Participants | 12 Participants | 7 Participants |
| Histopathological Classification of NSCLC Adenocarcinoma | 4 Participants | 4 Participants | 53 Participants | 33 Participants | 12 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 4 Participants | 53 Participants | 33 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 4 Participants | 4 Participants | 53 Participants | 33 Participants | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 35 Participants | 21 Participants | 9 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 18 Participants | 12 Participants | 3 Participants |
| Smoking History Former Smoker | 2 Participants | 2 Participants | 24 Participants | 16 Participants | 4 Participants |
| Smoking History Never Smoked | 2 Participants | 2 Participants | 29 Participants | 17 Participants | 8 Participants |
| Time Since Initial Diagnosis | 15.50 months | 26.90 months | 9.4 months | 1.90 months | 20.20 months |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 1 / 4 | 0 / 12 | 2 / 33 |
| other Total, other adverse events | 3 / 4 | 4 / 4 | 12 / 12 | 33 / 33 |
| serious Total, serious adverse events | 0 / 4 | 3 / 4 | 3 / 12 | 11 / 33 |
Outcome results
Primary
Phase 1 Part: Recommended Phase 2 Dose (RP2D) of Orally Administered Mobocertinib
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.
Time frame: Cycle 1 (Cycle length=28 days)
Population: The dose-limiting toxicity (DLT)-evaluable population included all participants who received at least 75 percent (%) of their planned mobocertinib doses for their first cycle of treatment (unless interrupted by study drug-related AEs). As planned, this outcome measure was assessed only for Phase 1 Part of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part: Recommended Phase 2 Dose (RP2D) of Orally Administered Mobocertinib | 160 mg |
Primary
Phase 2 Part: Confirmed Objective Response Rate (ORR) as Assessed by the Independent Review Committee (IRC)
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.
Time frame: From the first dose of the study drug until progressive disease (PD) (up to 2 years and 9 months)
Population: The centrally confirmed population was defined as the participants who had confirmed harboring EGFR exon 20 insertion mutation by central test and had received at least 1 dose of mobocertinib. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Confirmed Objective Response Rate (ORR) as Assessed by the Independent Review Committee (IRC) | 28.6 percentage of participants |
Secondary
Phase 1 Part, AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose
Time frame: Cycle 1 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days)
Population: The PK population included all participants for whom there were sufficient dosing and mobocertinib concentration-time data to reliably estimate the PK parameters. Here number analyzed 'n' signifies participants who were evaluable for specified categories. As planned, this outcome measure was assessed only for Phase 1 Part of the study.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32960 | 86.06 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 77.2 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Mobocertinib | 152.9 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 62.2 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32914 | 20.15 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 39.6 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32960 | 378.2 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 35.3 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Mobocertinib | 858.1 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 60.3 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32914 | 70.58 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 45.6 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Mobocertinib | 1196 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 43 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32914 | 105.9 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 44.5 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, AUC24: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32960 | 569.9 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 27.1 |
Secondary
Phase 1 Part, AUC24, ss: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses
Time frame: Cycle 2 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days)
Population: The PK population included all participants for whom there were sufficient dosing and mobocertinib concentration-time data to reliably estimate the PK parameters. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for Phase 1 Part of the study.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, AUC24, ss: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 158.6 h*ng/mL | Geometric Coefficient of Variation 63.1 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, AUC24, ss: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 214.8 h*ng/mL | Geometric Coefficient of Variation 29.9 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, AUC24, ss: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 21.02 h*ng/mL | Geometric Coefficient of Variation 24.3 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, AUC24, ss: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 794.0 h*ng/mL | Geometric Coefficient of Variation 36.6 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, AUC24, ss: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 1195 h*ng/mL | Geometric Coefficient of Variation 50.1 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, AUC24, ss: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 116.9 h*ng/mL | Geometric Coefficient of Variation 49.7 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, AUC24, ss: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 1141 h*ng/mL | Geometric Coefficient of Variation 25.9 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, AUC24, ss: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 105.0 h*ng/mL | Geometric Coefficient of Variation 20.4 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, AUC24, ss: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 750.3 h*ng/mL | Geometric Coefficient of Variation 27.4 |
Secondary
Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose
Time frame: Cycle 1 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days)
Population: The pharmacokinetic (PK) population included all participants for whom there were sufficient dosing and mobocertinib concentration-time data to reliably estimate the PK parameters. As planned, this outcome measure was assessed only for Phase 1 Part of the study
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32960 | 8.797 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 96.4 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Mobocertinib | 15.40 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 76.1 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32914 | 1.677 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 66.2 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32960 | 28.81 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Mobocertinib | 70.28 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 56.2 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32914 | 4.962 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41.7 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Mobocertinib | 100.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 36.3 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32914 | 8.626 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40.6 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32960 | 47.84 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28.9 |
Secondary
Phase 1 Part, Cmax, ss: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses
Time frame: Cycle 2 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days)
Population: The PK population included all participants for whom there were sufficient dosing and mobocertinib concentration-time data to reliably estimate the PK parameters. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for Phase 1 Part of the study.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Cmax, ss: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 1.808 ng/mL | Geometric Coefficient of Variation 31.4 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Cmax, ss: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 17.90 ng/mL | Geometric Coefficient of Variation 34.4 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Cmax, ss: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 12.34 ng/mL | Geometric Coefficient of Variation 68.7 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Cmax, ss: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 59.94 ng/mL | Geometric Coefficient of Variation 24.3 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Cmax, ss: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 9.198 ng/mL | Geometric Coefficient of Variation 37.7 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Cmax, ss: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 106.2 ng/mL | Geometric Coefficient of Variation 39.4 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Cmax, ss: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 90.00 ng/mL | Geometric Coefficient of Variation 18.4 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Cmax, ss: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 7.920 ng/mL | Geometric Coefficient of Variation 13.3 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Cmax, ss: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 56.85 ng/mL | Geometric Coefficient of Variation 21 |
Secondary
Phase 1 Part: Maximum Tolerated Dose (MTD) of Orally Administered Mobocertinib
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.
Time frame: Cycle 1 (Cycle length=28 days)
Population: The DLT-evaluable population was defined as all participants who received at least 75% of their planned mobocertinib doses for their first cycle of treatment (unless interrupted by study drug-related AEs). As planned, this outcome measure was assessed only for Phase 1 Part of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part: Maximum Tolerated Dose (MTD) of Orally Administered Mobocertinib | 160 mg |
Secondary
Phase 1 Part: Number of DLTs for Mobocertinib Based on NCI CTCAE, Version 5.00
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.
Time frame: Cycle 1 (Cycle length=28 days)
Population: The DLT-evaluable population included as all participants who received at least 75% of their planned mobocertinib doses for their first cycle of treatment (unless interrupted by study drug-related AEs). As planned, this outcome measure was assessed only for Phase 1 Part of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part: Number of DLTs for Mobocertinib Based on NCI CTCAE, Version 5.00 | 0 DLTs |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part: Number of DLTs for Mobocertinib Based on NCI CTCAE, Version 5.00 | 1 DLTs |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part: Number of DLTs for Mobocertinib Based on NCI CTCAE, Version 5.00 | 4 DLTs |
Secondary
Phase 1 Part: Number of Participants With First Cycle DLTs Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.00
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.
Time frame: Cycle 1 (Cycle length=28 days)
Population: The DLT-evaluable population included as all participants who received at least 75% of their planned mobocertinib doses for their first cycle of treatment (unless interrupted by study drug-related AEs). As planned, this outcome measure was assessed only for Phase 1 Part of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part: Number of Participants With First Cycle DLTs Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.00 | 0 Participants |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part: Number of Participants With First Cycle DLTs Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.00 | 1 Participants |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part: Number of Participants With First Cycle DLTs Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.00 | 2 Participants |
Secondary
Phase 1 Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug until 30 days after the last dose or before initiation of new anticancer therapy (whichever comes first) (Up to 2 years and 9 months, till data cut-off of 08 November 2021)
Population: The safety population included all participants who received at least 1 dose of mobocertinib. As planned, this outcome measure was assessed only for Phase 1 Part of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 4 Participants |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 12 Participants |
Secondary
Phase 1 Part: ORR in Participants With EGFR Mutations as Assessed by Investigator
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.
Time frame: From the first dose of the study drug until PD (up to 2 years and 9 months, till data cut-off of 08 November 2021)
Population: The response-evaluable population was defined as participants who received at least 1 dose of mobocertinib, had measurable disease at baseline, and at least 1 post-baseline response assessment. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for Phase 1 Part of study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part: ORR in Participants With EGFR Mutations as Assessed by Investigator | 0.0 percentage of participants |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part: ORR in Participants With EGFR Mutations as Assessed by Investigator | 25.0 percentage of participants |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part: ORR in Participants With EGFR Mutations as Assessed by Investigator | 18.2 percentage of participants |
Secondary
Phase 1 Part: ORR in Participants With HER2 Mutations as Assessed by Investigator
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.
Time frame: From the first dose of the study drug until PD (up to 2 years and 9 months, till data cut-off of 08 November 2021)
Population: The response-evaluable population was defined as participants who received at least 1 dose of mobocertinib, had measurable disease at baseline, and at least 1 post-baseline response assessment. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for Phase 1 Part of study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part: ORR in Participants With HER2 Mutations as Assessed by Investigator | 0 percentage of participants |
Secondary
Phase 1 Part, Rac (AUC 24): Extent of Accumulation Ratio Based on AUC 24 on Multiple Dosing for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses
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.
Time frame: Cycle 2 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days)
Population: The PK population included all participants for whom there were sufficient dosing and mobocertinib concentration-time data to reliably estimate the PK parameters. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for Phase 1 Part of the study.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Rac (AUC 24): Extent of Accumulation Ratio Based on AUC 24 on Multiple Dosing for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 1.393 ratio | Geometric Coefficient of Variation 17.5 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Rac (AUC 24): Extent of Accumulation Ratio Based on AUC 24 on Multiple Dosing for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 1.096 ratio | Geometric Coefficient of Variation 43.8 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Rac (AUC 24): Extent of Accumulation Ratio Based on AUC 24 on Multiple Dosing for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 1.044 ratio | Geometric Coefficient of Variation 41.7 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Rac (AUC 24): Extent of Accumulation Ratio Based on AUC 24 on Multiple Dosing for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 1.765 ratio | Geometric Coefficient of Variation 2 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Rac (AUC 24): Extent of Accumulation Ratio Based on AUC 24 on Multiple Dosing for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 1.260 ratio | Geometric Coefficient of Variation 12.9 |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Rac (AUC 24): Extent of Accumulation Ratio Based on AUC 24 on Multiple Dosing for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 1.414 ratio | Geometric Coefficient of Variation 21.2 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Rac (AUC 24): Extent of Accumulation Ratio Based on AUC 24 on Multiple Dosing for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 0.9227 ratio | Geometric Coefficient of Variation 39.3 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Rac (AUC 24): Extent of Accumulation Ratio Based on AUC 24 on Multiple Dosing for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 1.027 ratio | Geometric Coefficient of Variation 34.5 |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Rac (AUC 24): Extent of Accumulation Ratio Based on AUC 24 on Multiple Dosing for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 1.366 ratio | Geometric Coefficient of Variation 15.9 |
Secondary
Phase 1 Part, Tmax, ss: Time of First Occurrence of Cmax for Mobocertinib Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses
Time frame: Cycle 2 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days)
Population: The PK population included all participants for whom there were sufficient dosing and mobocertinib concentration-time data to reliably estimate the PK parameters. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for Phase 1 Part of the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Tmax, ss: Time of First Occurrence of Cmax for Mobocertinib Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 3.950 hour |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Tmax, ss: Time of First Occurrence of Cmax for Mobocertinib Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 3.950 hour |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Tmax, ss: Time of First Occurrence of Cmax for Mobocertinib Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 3.950 hour |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Tmax, ss: Time of First Occurrence of Cmax for Mobocertinib Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 4.000 hour |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Tmax, ss: Time of First Occurrence of Cmax for Mobocertinib Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 4.000 hour |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Tmax, ss: Time of First Occurrence of Cmax for Mobocertinib Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 4.000 hour |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Tmax, ss: Time of First Occurrence of Cmax for Mobocertinib Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | Mobocertinib | 3.970 hour |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Tmax, ss: Time of First Occurrence of Cmax for Mobocertinib Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32914 | 3.980 hour |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Tmax, ss: Time of First Occurrence of Cmax for Mobocertinib Its Active Metabolites (AP32960 and AP32914) at Steady State After Multiple Oral Doses | AP32960 | 3.970 hour |
Secondary
Phase 1 Part, Tmax: Time of First Occurrence of Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose
Time frame: Cycle 1 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days)
Population: The PK population included all participants for whom there were sufficient dosing and mobocertinib concentration-time data to reliably estimate the PK parameters. As planned, this outcome measure was assessed only for Phase 1 Part of the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Tmax: Time of First Occurrence of Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32960 | 3.830 hour |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Tmax: Time of First Occurrence of Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Mobocertinib | 3.830 hour |
| Mobocertinib, Phase 1 Part: All Participants | Phase 1 Part, Tmax: Time of First Occurrence of Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32914 | 3.830 hour |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Tmax: Time of First Occurrence of Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32960 | 3.985 hour |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Tmax: Time of First Occurrence of Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Mobocertinib | 3.985 hour |
| Mobocertinib 120 mg, Phase 1 Part | Phase 1 Part, Tmax: Time of First Occurrence of Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32914 | 4.995 hour |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Tmax: Time of First Occurrence of Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | Mobocertinib | 3.985 hour |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Tmax: Time of First Occurrence of Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32914 | 4.965 hour |
| Mobocertinib 160 mg, Phase 1 Part | Phase 1 Part, Tmax: Time of First Occurrence of Cmax for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose | AP32960 | 4.965 hour |
Secondary
Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30
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).
Time frame: Baseline and at 30 days after last dose (at Month 19)
Population: FAS included all participants who received at least one dose of mobocertinib. Here number analyzed 'n' signifies participants who were evaluable for specified categories. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Global Health Status: Baseline | 64.7 score on a scale | Standard Deviation 18.79 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Global Health Status: Change from Baseline at 30 Days After Last Dose | -4.0 score on a scale | Standard Deviation 17.45 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Physical Functioning: Baseline | 85.5 score on a scale | Standard Deviation 14.03 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Physical Functioning: Change from Baseline at 30 Days After Last Dose | -34.6 score on a scale | Standard Deviation 40.38 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Role Functioning: Baseline | 80.3 score on a scale | Standard Deviation 25.78 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Role Functioning: Change from Baseline at 30 Days After Last Dose | -53.4 score on a scale | Standard Deviation 50.57 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Emotional Functioning: Baseline | 80.8 score on a scale | Standard Deviation 20.13 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Emotional Functioning: Change from Baseline at 30 Days After Last Dose | -6.0 score on a scale | Standard Deviation 12 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Cognitive Functioning: Baseline | 84.2 score on a scale | Standard Deviation 16.09 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Cognitive Functioning: Change from Baseline at 30 Days After Last Dose | 4.3 score on a scale | Standard Deviation 8.5 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Social Functioning: Baseline | 87.4 score on a scale | Standard Deviation 18.54 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Social Functioning: Change from Baseline at 30 Days After Last Dose | -12.5 score on a scale | Standard Deviation 15.84 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Fatigue: Baseline | 27.8 score on a scale | Standard Deviation 20.85 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Fatigue: Change from Baseline at 30 Days After Last Dose | 29.0 score on a scale | Standard Deviation 38.28 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Nausea and Vomiting: Baseline | 3.6 score on a scale | Standard Deviation 12.42 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Nausea and Vomiting: Change from Baseline at 30 Days After Last Dose | 0.0 score on a scale | Standard Deviation 12.02 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Pain: Baseline | 19.2 score on a scale | Standard Deviation 21.21 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Pain: Change from Baseline at 30 Days After Last Dose | 9.6 score on a scale | Standard Deviation 18.9 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Dyspnoea: Baseline | 23.1 score on a scale | Standard Deviation 26.94 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Dyspnoea: Change from Baseline at 30 Days After Last Dose | 13.6 score on a scale | Standard Deviation 38.11 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Insomnia: Baseline | 26.2 score on a scale | Standard Deviation 24.72 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Insomnia: Change from Baseline at 30 Days After Last Dose | 20.2 score on a scale | Standard Deviation 50.51 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Appetite Loss: Baseline | 22.1 score on a scale | Standard Deviation 25.91 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Appetite Loss: Change from Baseline at 30 Days After Last Dose | 20.2 score on a scale | Standard Deviation 30.02 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Constipation: Baseline | 14.1 score on a scale | Standard Deviation 23.56 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Constipation: Change from Baseline at 30 Days After Last Dose | -6.8 score on a scale | Standard Deviation 27.85 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Diarrhoea: Baseline | 6.0 score on a scale | Standard Deviation 15.46 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Diarrhoea: Change from Baseline at 30 Days After Last Dose | -8.3 score on a scale | Standard Deviation 31.6 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Financial Difficulties: Baseline | 9.0 score on a scale | Standard Deviation 14.92 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 | Financial Difficulties: Change from Baseline at 30 Days After Last Dose | 8.3 score on a scale | Standard Deviation 16.5 |
Secondary
Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13
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.
Time frame: Baseline and at 30 days after last dose (at Month 19)
Population: The full analysis set (FAS) included all participants who received at least one dose of mobocertinib. Here number analyzed 'n' signifies participants who were evaluable for specified categories. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Dyspnoea: Baseline | 16.4 score on a scale | Standard Deviation 15.76 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Dyspnoea: Change from Baseline at 30 Days After Last Dose | 2.8 score on a scale | Standard Deviation 18.79 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Coughing: Baseline | 27.1 score on a scale | Standard Deviation 24.24 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Coughing: Change from Baseline at 30 Days After Last Dose | -8.5 score on a scale | Standard Deviation 41.99 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Haemoptysis: Baseline | 2.0 score on a scale | Standard Deviation 8 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Haemoptysis: Change from Baseline at 30 Days After Last Dose | 0.0 score on a scale | Standard Deviation 0 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Sore Mouth: Baseline | 5.0 score on a scale | Standard Deviation 12.02 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Sore Mouth: Change from Baseline at 30 Days After Last Dose | 0.0 score on a scale | Standard Deviation 0 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Dysphagia: Baseline | 7.0 score on a scale | Standard Deviation 13.7 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Dysphagia: Change from Baseline at 30 Days After Last Dose | 0.0 score on a scale | Standard Deviation 0 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Peripheral Neuropathy: Baseline | 6.0 score on a scale | Standard Deviation 15.46 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Peripheral Neuropathy: Change from Baseline at 30 Days After Last Dose | -8.3 score on a scale | Standard Deviation 16.5 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Alopecia: Baseline | 9.0 score on a scale | Standard Deviation 20.8 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Alopecia: Change from Baseline at 30 Days After Last Dose | 0.0 score on a scale | Standard Deviation 0 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Pain in Chest: Baseline | 14.1 score on a scale | Standard Deviation 20.42 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Pain in Chest: Change from Baseline at 30 Days After Last Dose | -8.3 score on a scale | Standard Deviation 16.5 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Pain in Arm or Shoulder: Baseline | 17.0 score on a scale | Standard Deviation 18.75 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Pain in Arm or Shoulder: Change from Baseline at 30 Days After Last Dose | -8.3 score on a scale | Standard Deviation 16.5 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Pain in Other Parts: Baseline | 18.1 score on a scale | Standard Deviation 22.17 |
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Change From Baseline in Patient-reported Symptoms (Particular Core Symptoms of Lung Cancer), Functioning, and HRQoL as Assessed by the EORTC Lung Cancer Module QLQ-LC13 | Pain in Other Parts: Change from Baseline at 30 Days After Last Dose | -8.3 score on a scale | Standard Deviation 16.5 |
Secondary
Phase 2 Part: Confirmed ORR as Assessed by the Investigator
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.
Time frame: From the first dose of the study drug until PD (up to 2 years and 9 months, till data cut-off of 08 November 2021)
Population: The centrally confirmed population was defined as the participants who had confirmed harboring EGFR exon 20 insertion mutation by central test and had received at least 1 dose of mobocertinib. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Confirmed ORR as Assessed by the Investigator | 43.5 percentage of participants |
Secondary
Phase 2 Part: DCR as Assessed by the Investigator Per RECIST V1.1
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.
Time frame: From the first dose of the study drug until PD (Up to 2 years 9 month, till data cut-off of 08 November 2021)
Population: The centrally confirmed population was defined as the participants who had confirmed harboring EGFR exon 20 insertion mutation by central test and had received at least 1 dose of mobocertinib. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: DCR as Assessed by the Investigator Per RECIST V1.1 | 91.3 percentage of participants |
Secondary
Phase 2 Part: Disease Control Rate (DCR) as Assessed by the IRC as Per RECIST V1.1
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.
Time frame: From the first dose of the study drug until PD (Up to 2 years 9 month, till data cut-off of 08 November 2021)
Population: The centrally confirmed population was defined as the participants who had confirmed harboring EGFR exon 20 insertion mutation by central test and had received at least 1 dose of mobocertinib. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Disease Control Rate (DCR) as Assessed by the IRC as Per RECIST V1.1 | 82.6 percentage of participants |
Secondary
Phase 2 Part: DOR as Assessed by Investigator as Per RECIST V1.1
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 frame: From first documentation of CR/PR until first PD (Up to 2 years and 9 months, till data cut-off of 08 November 2021)
Population: The centrally confirmed population was defined as the participants who had confirmed harboring EGFR exon 20 insertion mutation by central test and had received at least 1 dose of mobocertinib. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: DOR as Assessed by Investigator as Per RECIST V1.1 | 6.6 months |
Secondary
Phase 2 Part: Duration of Response (DOR) as Assessed by the IRC as Per RECIST V1.1
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.
Time frame: From first documentation of CR/PR until first PD (Up to 2 years and 9 months, till data cut-off of 08 November 2021)
Population: The centrally confirmed population was defined as the participants who had confirmed harboring EGFR exon 20 insertion mutation by central test and had received at least 1 dose of mobocertinib. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Duration of Response (DOR) as Assessed by the IRC as Per RECIST V1.1 | 7.4 months |
Secondary
Phase 2 Part: Overall Survival (OS)
OS was defined as the interval from the date of the first dose of the study treatment until death due to any cause.
Time frame: From the start of the study drug up to death due to any cause (Up to 2 years 9 months, till data cut-off of 08 November 2021)
Population: The centrally confirmed population was defined as the participants who had confirmed harboring EGFR exon 20 insertion mutation by central test and had received at least 1 dose of mobocertinib. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Overall Survival (OS) | NA months |
Secondary
Phase 2 Part: PFS as Assessed by the Investigator as Per RECIST V1.1
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.
Time frame: From the first dose of the study drug until PD or death due to any cause (whichever comes first) (Up to 2 years and 9 months, till data cut-off of 08 November 2021
Population: The centrally confirmed population was defined as the participants who had confirmed harboring EGFR exon 20 insertion mutation by central test and had received at least 1 dose of mobocertinib. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: PFS as Assessed by the Investigator as Per RECIST V1.1 | 9.2 months |
Secondary
Phase 2 Part: Progression Free Survival (PFS) as Assessed by the IRC as Per RECIST V1.1
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.
Time frame: From the first dose of the study drug until PD or death due to any cause (whichever comes first) (Up to 2 years and 9 months, till data cut-off of 08 November 2021
Population: The centrally confirmed population was defined as the participants who had confirmed harboring EGFR exon 20 insertion mutation by central test and had received at least 1 dose of mobocertinib. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Progression Free Survival (PFS) as Assessed by the IRC as Per RECIST V1.1 | 9.3 months |
Secondary
Phase 2 Part: Time to Response as Assessed by the Investigator Per RECIST V1.1
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.
Time frame: From the first dose of the study drug up to first confirmed CR or PR (Up to 2 years 9 months, till data cut-off of 08 November 2021)
Population: The centrally confirmed population was defined as the participants who had confirmed harboring EGFR exon 20 insertion mutation by central test and had received at least 1 dose of mobocertinib. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Time to Response as Assessed by the Investigator Per RECIST V1.1 | 57.0 days |
Secondary
Phase 2 Part: Time to Response as Assessed by the IRC as Per RECIST V1.1
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 frame: From the first dose of the study drug up to first confirmed CR or PR (Up to 2 years 9 months, till data cut-off of 08 November 2021)
Population: The centrally confirmed population was defined as the participants who had confirmed harboring EGFR exon 20 insertion mutation by central test and had received at least 1 dose of mobocertinib. Here, Overall number of participants analyzed signifies participants who were evaluable for this outcome measure. As planned, this outcome measure was assessed only for Phase 2 Part of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mobocertinib, Phase 1 Part: All Participants | Phase 2 Part: Time to Response as Assessed by the IRC as Per RECIST V1.1 | 52.0 days |