Malignant Pleural Mesothelioma, Non-Small Cell Lung Cancer
Conditions
Brief summary
This is an open-label, multicenter, phase 1/2 study of BBI608 in combination with pemetrexed and cisplatin chemotherapy as a 1st line treatment for Malignant Pleural Mesothelioma (MPM).
Interventions
DRUGCisplatin
75 mg/m2 I.V. infusion on Day 1 of each treatment cycle (except for Cycle 1, in which Cisplatin will be given on Day 3).
DRUGBBI608
480 mg orally twice daily (960 mg total daily dose)
DRUGPemetrexed
500 mg/m2 I.V. infusion on Day 1 of each treatment cycle (except for cycle 1, in which Pemetrexed will be given on Day 3).
Sponsors
Sumitomo Pharma Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase 1 Inclusion Criteria: * Histologically confirmed diagnosis of Malignant Pleural Mesothelioma (MPM) or Non-Small Cell Lung Cancer (NSCLC). * Measurable disease as defined by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) for MPM or the RECIST 1.1 for NSCLC. * ≥ 20 years of age. * Provision of written informed consent. * For male or female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days after the last protocol treatment dose. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. * Hemoglobin (Hb) ≥ 9.0 g/dL. * Neutrophils ≥ 1500/μL. * Platelets ≥ 100,000/μL. * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5-fold the upper limit of normal range (ULN) \[≤ 5-fold ULN with any liver metastasis\]. * Total bilirubin ≤ 1.5-fold ULN. * Creatinine clearance (estimated value) ≥ 60 mL/min. * Life expectancy ≥ 3 months. * Females of childbearing potential have a negative urine pregnancy test. Phase 2 Inclusion Criteria: * Histologically confirmed diagnosis of MPM. * Treatment naïve and not indicated for resection. * Measurable disease as defined by the modified RECIST. * ≥ 20 years of age. * Provision of written informed consent. * For male or female patient of child producing potential: Must agree to use contraception or take measures to avoid pregnancy during the study and for 30 days after the last protocol treatment dose. * ECOG Performance Status of 0 or 1. * Hb ≥ 9.0 g/dL. * Neutrophils ≥ 1500/μL. * Platelets ≥ 100,000/μL. * AST and ALT ≤ 2.5-fold ULN \[≤ 5-fold ULN for patients with any liver metastasis\]. * Total bilirubin ≤ 1.5-fold ULN. * Creatinine clearance (estimated value) \> 60 mL/min. * Life expectancy ≥ 3 months. * Females of childbearing potential have a negative urine pregnancy test. Both Phase 1 and 2
Exclusion criteria
* Prior anti-cancer chemotherapy and radiotherapy. * Prior hormonal therapy, immunotherapy, thermotherapy, operation. * Any brain metastasis requiring treatment or symptomatic. * Active multiple primary cancers. * Crohn's disease, ulcerative colitis, small intestine resection. * Abnormal ECGs. * Prior myocardial infarction. * Current use of antiarrhythmic medication. * Uncontrolled concurrent diseases. * Known severe hypersensitivity to pemetrexed, cisplatin or other drugs containing platinum. * Women who are pregnant or breastfeeding. * Received other investigational drugs. * Unable or unwilling to swallow BBI608 capsules daily. * Prior treatment with BBI608. * Ineligible for participation in the study in the opinion of the Investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2 Part: Progression-free Survival (PFS) | From BBI608 administration to documented PD or death, whichever is earlier, about 17 months | PFS was defined as the time from BBI608 administration to documented PD (as assessed according to the mRECIST or RECIST 1.1) or death, whichever is earlier. The result of imaging assessment by the imaging assessment committee was used for phase 2 part. |
| Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | Between initial dosing of the investigational drug and final evaluation in the follow-up observation period, about 17 months | An AE is any untoward medical occurrence in a study subject administered an investigational drug and which does not necessarily have a causal relationship with this treatment. A SAE was an AE that met one or more of the following criteria: * Results in death * Is life-threatening * Requires hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability or incapacity * Is a congenital anomaly or birth defect * Is an important medical event that may jeopardize the subject or may require a medical or surgical intervention to prevent one of the outcomes listed above. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization. An ADR was defined as adverse events assessed to be related to the investigational drug |
| Phase 1 Part: Number of Participants With Dose-limiting Toxicities (DLTs) | From Day 1 of Cycle 1 to Day 24 pre-dose examination (23 days) | DLT was defined as an adverse event meeting any of the following that occurred during the DLT evaluation period in any participants given BBI608 with the causal relationship to BBI608 assessed as Definite, Probable, or Possible. The severity of adverse events was graded according to the CTCAE v4.0-JCOG. * Grade 4 neutropenia persisting for ≥ 7 days * Grade ≥ 3 febrile neutropenia persisting for ≥ 5 days * Grade 3 thrombocytopenia requiring platelet transfusions, grade 4 thrombocytopenia * Grade ≥ 3 non-hematotoxicity except the following: 1. Inappetence, nausea, vomiting and electrolyte abnormality which, within 3 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment 2. Diarrhoea and fatigue which, within 5 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment * Other clinically significant signs in the opinion of the investigator |
| Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP | Cycle 1 Day 1 (Cmax only) and Day 23 | — |
| Phase 1 Part: Area Under the Concentration-time Curve | Cycle 1 Day 1 and Day 23 | AUC0-12: Area under the concentration-time curve from time zero to 12 hours, AUC0-24: Area under the concentration-time curve from time zero to 24 hours, AUC0-inf: Area under the concentration-time curve from time zero to infinity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (RR) and Disease Control Rate (DCR) | From BBI608 administration to death from any cause, about 17 months | Response rate (RR): Proportion of subjects whose best overall response is CR or PR. Disease control rate (DCR): Proportion of subjects whose best overall response is CR, PR or SD. The result of imaging assessment by study site was used for phase 1 part, and the result of imaging assessment by the imaging assessment committee was used for phase 2 part. |
| Best Overall Response | Every 6 weeks from the first dose of BBI608 until Week 30, and every 9 weeks from Week 31. | The best overall response is the best response recorded from the start of the study treatment until the end of treatment. The RECIST 1.1 was used for the evaluation of tumor response and overall response in patients with NSCLC, and also the evaluation of any non-pleural lesions in patients with MPM. The mRECIST was used for the evaluation of tumor response and overall response in patients with MPM. The result of imaging assessment by study site was used for phase 1 part, and the result of imaging assessment by the imaging assessment committee was used for phase 2 part. |
| Overall Survival(OS) | From BBI608 administration to death from any cause, up to 31 months | OS was defined as the time from BBI608 administration to death from any cause. Participants alive at final observation or lost to follow-up were censored at their last contact (i.e., visit or telephone) date. |
| Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | Every 6 weeks from the first dose of BBI608 until Week 30, and then every 9 weeks from Week 31 [Actually up to Week 111] | — |
| Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | Every 6 weeks from the first dose of BBI608 until Week 30, and then every 9 weeks from Week 31 [Actually up to Week 111] | — |
Countries
Japan
Participant flow
Recruitment details
The study conducted from February 2015 to December 2017 and a total of 28 participants were enrolled at 9 medical institutions in Japan.
Pre-assignment details
This clinical study consisted of two parts: Phase 1 and Phase 2. The study proceeded to Phase 2 part after Phase 1 part demonstrated the tolerability of BBI608 combined with Pem plus CDDP based on complete assessment of DLT. Participants were NOT enrolled in Phase 1 and Phase 2 in duplicate.
Participants by arm
| Arm | Count |
|---|---|
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles.
Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | 4 |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) Participants orally received BBI608 (480 mg) twice daily plus intravenously received Pem (500 mg/m2) and CDDP (75 mg/m2) on Day 3 in only Cycles 1 and on Days 1 in Cycles 2 and subsequent cycles.
Premeditation with folic acid and vitamin B12 was given to reduce occurrence of serious adverse drug reactions, with reference to the package insert for Pem. Each cycle was defined as 21 days. | 24 |
| Total | 28 |
Baseline characteristics
| Characteristic | MPM: BBI608 + Pem + CDDP (Phase 2 Part) | MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Total |
|---|---|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 10.71 | 64.5 years STANDARD_DEVIATION 5 | 65.5 years STANDARD_DEVIATION 9.854 |
| Disease classification MPM STAGE I | 0 Participants | 0 Participants | 0 Participants |
| Disease classification MPM STAGE II | 2 Participants | 0 Participants | 2 Participants |
| Disease classification MPM STAGE III | 5 Participants | 0 Participants | 5 Participants |
| Disease classification MPM STAGE IV | 17 Participants | 1 Participants | 18 Participants |
| Disease classification NSCLC STAGE I | 0 Participants | 0 Participants | 0 Participants |
| Disease classification NSCLC STAGE II | 0 Participants | 0 Participants | 0 Participants |
| Disease classification NSCLC STAGE III | 0 Participants | 0 Participants | 0 Participants |
| Disease classification NSCLC STAGE IV | 0 Participants | 3 Participants | 3 Participants |
| Disease duration | 0.91 month STANDARD_DEVIATION 0.726 | 3.91 month STANDARD_DEVIATION 2.866 | 1.34 month STANDARD_DEVIATION 1.562 |
| ECOG PS 0 | 11 Participants | 3 Participants | 14 Participants |
| ECOG PS 1 | 13 Participants | 1 Participants | 14 Participants |
| ECOG PS 2<= | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 4 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Metastases No | 13 Participants | 1 Participants | 14 Participants |
| Metastases Yes | 11 Participants | 3 Participants | 14 Participants |
| Primary cancer MPM | 24 Participants | 1 Participants | 25 Participants |
| Primary cancer NSCLC | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 24 Participants | 4 Participants | 28 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 22 Participants | 3 Participants | 25 Participants |
| Tissue classification (MPM) BIPHASIC | 5 Participants | 0 Participants | 5 Participants |
| Tissue classification (MPM) EPITHELIOID | 16 Participants | 1 Participants | 17 Participants |
| Tissue classification (MPM) OTHER | 0 Participants | 0 Participants | 0 Participants |
| Tissue classification (MPM) SARCOMATOID | 3 Participants | 0 Participants | 3 Participants |
| Tissue classification (NSCLC) ADENOCARCINOMA | 0 Participants | 3 Participants | 3 Participants |
| Tissue classification (NSCLC) LARGE CELL CARCINOMA | 0 Participants | 0 Participants | 0 Participants |
| Tissue classification (NSCLC) OTHER | 0 Participants | 0 Participants | 0 Participants |
| Tissue classification (NSCLC) SQUAMOUS CELL CARCINOMA | 0 Participants | 0 Participants | 0 Participants |
| Weight | 63.11 kg STANDARD_DEVIATION 7.661 | 58.53 kg STANDARD_DEVIATION 10.278 | 62.45 kg STANDARD_DEVIATION 8.025 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 4 | 19 / 24 | 21 / 25 |
| other Total, other adverse events | 4 / 4 | 24 / 24 | 25 / 25 |
| serious Total, serious adverse events | 0 / 4 | 7 / 24 | 7 / 25 |
Outcome results
Primary
Phase 1 Part: Area Under the Concentration-time Curve
AUC0-12: Area under the concentration-time curve from time zero to 12 hours, AUC0-24: Area under the concentration-time curve from time zero to 24 hours, AUC0-inf: Area under the concentration-time curve from time zero to infinity
Time frame: Cycle 1 Day 1 and Day 23
Population: Pharmacokinetic (PK) analysis population~1 participant with MPM of 4 participants in the pharmacokinetic analysis population completed BBI608 administration on Day 14 in Cycle 1 and therefore was not included in the analysis for Cmax and AUC on Day 23.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Area Under the Concentration-time Curve | Day 23: AUC0-24 | 6103.7 h*ng/mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Area Under the Concentration-time Curve | Day 23: AUC0-inf | 10762.7 h*ng/mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Area Under the Concentration-time Curve | Day 1: AUC0-12 | 1814.3 h*ng/mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Area Under the Concentration-time Curve | Day 1: AUC0-24 | 2223.8 h*ng/mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Area Under the Concentration-time Curve | Day 1: AUC0-inf | 2413.5 h*ng/mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Area Under the Concentration-time Curve | Day 23: AUC0-12 | 3797.0 h*ng/mL |
Primary
Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP
Time frame: Cycle 1 Day 1 (Cmax only) and Day 23
Population: Pharmacokinetic (PK) analysis population~1 participant with MPM of 4 participants in the pharmacokinetic analysis population completed BBI608 administration on Day 14 in Cycle 1 and therefore was not included in the analysis for Cmax and AUC on Day 23.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP | Day 1: Cmax | 307.5 ng/mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP | Day 23: Cmax | 473.7 ng/mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of BBI608 When Administered With Pem and CDDP | Day 23: Cmin | 196.1 ng/mL |
Primary
Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs)
An AE is any untoward medical occurrence in a study subject administered an investigational drug and which does not necessarily have a causal relationship with this treatment. A SAE was an AE that met one or more of the following criteria: * Results in death * Is life-threatening * Requires hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability or incapacity * Is a congenital anomaly or birth defect * Is an important medical event that may jeopardize the subject or may require a medical or surgical intervention to prevent one of the outcomes listed above. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization. An ADR was defined as adverse events assessed to be related to the investigational drug
Time frame: Between initial dosing of the investigational drug and final evaluation in the follow-up observation period, about 17 months
Population: Safety analysis populations (Phase 1 part)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | AEs leading to drug interrupted (BBI608) | 1 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | AEs leading to dose reduced (BBI608) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | ADRs leading to death | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | ADRs leading to dose reduced (BBI608) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | Any AEs | 4 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | AEs leading to death | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | Serious AEs | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | AEs leading to drug withdrawn (BBI608) | 1 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | Any ADRs | 4 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | Serious ADRs | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | ADRs leading to drug withdrawn (BBI608) | 1 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Drug Reactions (ADRs) | ADRs leading to drug interrupted (BBI608) | 1 Participants |
Primary
Phase 1 Part: Number of Participants With Dose-limiting Toxicities (DLTs)
DLT was defined as an adverse event meeting any of the following that occurred during the DLT evaluation period in any participants given BBI608 with the causal relationship to BBI608 assessed as Definite, Probable, or Possible. The severity of adverse events was graded according to the CTCAE v4.0-JCOG. * Grade 4 neutropenia persisting for ≥ 7 days * Grade ≥ 3 febrile neutropenia persisting for ≥ 5 days * Grade 3 thrombocytopenia requiring platelet transfusions, grade 4 thrombocytopenia * Grade ≥ 3 non-hematotoxicity except the following: 1. Inappetence, nausea, vomiting and electrolyte abnormality which, within 3 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment 2. Diarrhoea and fatigue which, within 5 days of onset, improved to grade ≤ 2 or resolved after appropriate treatment * Other clinically significant signs in the opinion of the investigator
Time frame: From Day 1 of Cycle 1 to Day 24 pre-dose examination (23 days)
Population: DLT evaluable population (3 participants with NSCLC in Phase 1 part)~1 participant with MPM was excluded from DLT evaluable population because the BBI608 treatment compliance rate during DLT evaluation period did not meet the rate of 80% which of assessable for DLT and no adverse events assessed as DLT occurred.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 1 Part: Number of Participants With Dose-limiting Toxicities (DLTs) | 0 Participants |
Primary
Phase 2 Part: Progression-free Survival (PFS)
PFS was defined as the time from BBI608 administration to documented PD (as assessed according to the mRECIST or RECIST 1.1) or death, whichever is earlier. The result of imaging assessment by the imaging assessment committee was used for phase 2 part.
Time frame: From BBI608 administration to documented PD or death, whichever is earlier, about 17 months
Population: modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Phase 2 Part: Progression-free Survival (PFS) | 5.59 month |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | Phase 2 Part: Progression-free Survival (PFS) | 5.59 month |
Secondary
Best Overall Response
The best overall response is the best response recorded from the start of the study treatment until the end of treatment. The RECIST 1.1 was used for the evaluation of tumor response and overall response in patients with NSCLC, and also the evaluation of any non-pleural lesions in patients with MPM. The mRECIST was used for the evaluation of tumor response and overall response in patients with MPM. The result of imaging assessment by study site was used for phase 1 part, and the result of imaging assessment by the imaging assessment committee was used for phase 2 part.
Time frame: Every 6 weeks from the first dose of BBI608 until Week 30, and every 9 weeks from Week 31.
Population: modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Best Overall Response | Stable disease (SD) | 3 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Best Overall Response | Complete response (CR) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Best Overall Response | Not evaluated (NE) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Best Overall Response | Partial response (PR) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Best Overall Response | Progressive disease (PD) | 0 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | Best Overall Response | Not evaluated (NE) | 1 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | Best Overall Response | Stable disease (SD) | 0 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | Best Overall Response | Partial response (PR) | 0 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | Best Overall Response | Progressive disease (PD) | 0 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | Best Overall Response | Complete response (CR) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Best Overall Response | Stable disease (SD) | 3 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Best Overall Response | Partial response (PR) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Best Overall Response | Complete response (CR) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Best Overall Response | Progressive disease (PD) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Best Overall Response | Not evaluated (NE) | 1 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Best Overall Response | Partial response (PR) | 8 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Best Overall Response | Not evaluated (NE) | 3 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Best Overall Response | Progressive disease (PD) | 2 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Best Overall Response | Complete response (CR) | 0 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Best Overall Response | Stable disease (SD) | 11 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Best Overall Response | Stable disease (SD) | 11 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Best Overall Response | Complete response (CR) | 0 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Best Overall Response | Partial response (PR) | 8 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Best Overall Response | Not evaluated (NE) | 4 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Best Overall Response | Progressive disease (PD) | 2 Participants |
Secondary
Overall Survival(OS)
OS was defined as the time from BBI608 administration to death from any cause. Participants alive at final observation or lost to follow-up were censored at their last contact (i.e., visit or telephone) date.
Time frame: From BBI608 administration to death from any cause, up to 31 months
Population: modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Overall Survival(OS) | 19.81 month |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | Overall Survival(OS) | 30.1 month |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Overall Survival(OS) | NA month |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Overall Survival(OS) | 12.14 month |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Overall Survival(OS) | 12.75 month |
Secondary
Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1])
Time frame: Every 6 weeks from the first dose of BBI608 until Week 30, and then every 9 weeks from Week 31 [Actually up to Week 111]
Population: modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25). In respiratory function tests, data from 1 participant with MPM in Phase 1 part were not collected.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 48 weeks | NA L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 39 weeks | -0.140 L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 66 weeks | NA L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 24 weeks | -0.010 L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 18 weeks | 0.000 L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 12 weeks | 0.070 L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 57 weeks | NA L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 30 weeks | -0.055 L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 6 weeks | 0.160 L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 30 weeks | -0.055 L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 48 weeks | NA L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 39 weeks | -0.140 L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 12 weeks | 0.070 L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 6 weeks | 0.160 L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 18 weeks | 0.000 L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 66 weeks | NA L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 57 weeks | NA L |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 24 weeks | -0.010 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 30 weeks | -0.030 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 6 weeks | 0.050 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 12 weeks | -0.130 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 18 weeks | -0.110 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 24 weeks | -0.040 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 39 weeks | -0.050 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 48 weeks | 0.115 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 57 weeks | 0.010 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 66 weeks | 0.085 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 75 weeks | -0.045 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 84 weeks | -0.130 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 93 weeks | -0.215 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 102 weeks | NA L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 111 weeks | NA L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 12 weeks | -0.130 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 6 weeks | 0.050 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 102 weeks | NA L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 66 weeks | 0.085 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 93 weeks | -0.215 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 75 weeks | -0.045 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 39 weeks | -0.050 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 30 weeks | -0.030 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 111 weeks | NA L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 48 weeks | 0.115 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 24 weeks | -0.040 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 18 weeks | -0.110 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 84 weeks | -0.130 L |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Forced Expiratory Volume in the First Second [FEV1]) | The change from baseline in FEV1: 57 weeks | 0.010 L |
Secondary
Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC])
Time frame: Every 6 weeks from the first dose of BBI608 until Week 30, and then every 9 weeks from Week 31 [Actually up to Week 111]
Population: modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25). In respiratory function tests, data from 1 participant with MPM in Phase 1 part were not collected.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 48 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 30 weeks | -265.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 6 weeks | 70.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 57 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 66 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 57 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 66 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 12 weeks | 110.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 39 weeks | -345.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 6 weeks | 0.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 24 weeks | -155.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 18 weeks | -60.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 12 weeks | 80.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 30 weeks | -240.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 24 weeks | -290.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 48 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 39 weeks | -305.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 18 weeks | -20.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 18 weeks | -60.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 48 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 48 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 39 weeks | -345.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 18 weeks | -20.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 57 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 24 weeks | -290.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 6 weeks | 70.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 12 weeks | 80.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 66 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 6 weeks | 0.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 57 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 30 weeks | -265.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 24 weeks | -155.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 39 weeks | -305.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 30 weeks | -240.0 mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 66 weeks | NA mL |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 12 weeks | 110.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 12 weeks | 0.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 24 weeks | -50.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 18 weeks | -70.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 30 weeks | 150.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 102 weeks | NA mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 39 weeks | -35.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 48 weeks | 70.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 57 weeks | 60.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 24 weeks | -50.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 66 weeks | 300.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 84 weeks | 10.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 75 weeks | 50.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 12 weeks | 10.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 30 weeks | 20.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 111 weeks | NA mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 39 weeks | 30.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 48 weeks | 15.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 57 weeks | -20.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 66 weeks | 300.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 6 weeks | 30.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 75 weeks | 175.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 93 weeks | -230.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 84 weeks | 145.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 93 weeks | -205.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 102 weeks | NA mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 18 weeks | -140.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 111 weeks | NA mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 6 weeks | 35.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 75 weeks | 50.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 12 weeks | 10.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 84 weeks | 10.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 93 weeks | -230.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 102 weeks | NA mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 111 weeks | NA mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 6 weeks | 30.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 12 weeks | 0.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 18 weeks | -70.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 24 weeks | -50.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 30 weeks | 20.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 39 weeks | 30.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 48 weeks | 15.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 57 weeks | -20.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 66 weeks | 300.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 75 weeks | 175.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 84 weeks | 145.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 93 weeks | -205.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 102 weeks | NA mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in VC: 111 weeks | NA mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 6 weeks | 35.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 18 weeks | -140.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 24 weeks | -50.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 30 weeks | 150.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 39 weeks | -35.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 48 weeks | 70.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 57 weeks | 60.0 mL |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Respiratory Function Tests (Vital Capacity [VC] and Forced Vital Capacity [FVC]) | The change from baseline in FVC: 66 weeks | 300.0 mL |
Secondary
Response Rate (RR) and Disease Control Rate (DCR)
Response rate (RR): Proportion of subjects whose best overall response is CR or PR. Disease control rate (DCR): Proportion of subjects whose best overall response is CR, PR or SD. The result of imaging assessment by study site was used for phase 1 part, and the result of imaging assessment by the imaging assessment committee was used for phase 2 part.
Time frame: From BBI608 administration to death from any cause, about 17 months
Population: modified ITT population. Efficacy was analyzed using the efficacy analysis population (i.e., modified ITT population; mITT), separately for Phase 1 part (n=4), Phase 2 part (n=24) and Phase 2 part including 1 participant with MPM in Phase 1 part (n=25).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Response Rate (RR) and Disease Control Rate (DCR) | Response rate (RR) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Response Rate (RR) and Disease Control Rate (DCR) | Disease control rate (DCR) | 3 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | Response Rate (RR) and Disease Control Rate (DCR) | Response rate (RR) | 0 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including 1 Participant With MPM in Phase 1 Part) | Response Rate (RR) and Disease Control Rate (DCR) | Disease control rate (DCR) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Response Rate (RR) and Disease Control Rate (DCR) | Response rate (RR) | 0 Participants |
| MPM or NSCLC: BBI608 + Pem + CDDP (Phase 1 Part) | Response Rate (RR) and Disease Control Rate (DCR) | Disease control rate (DCR) | 3 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Response Rate (RR) and Disease Control Rate (DCR) | Disease control rate (DCR) | 19 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part) | Response Rate (RR) and Disease Control Rate (DCR) | Response rate (RR) | 8 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Response Rate (RR) and Disease Control Rate (DCR) | Response rate (RR) | 8 Participants |
| MPM: BBI608 + Pem + CDDP (Phase 2 Part Including Participants With MPM in Phase 1 Part) | Response Rate (RR) and Disease Control Rate (DCR) | Disease control rate (DCR) | 19 Participants |