Cancer, Solid Tumor Clinical Trial
— KEYNOTE-001Official title:
Phase I Study of Single Agent Pembrolizumab (MK-3475) in Patients With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, and Non-Small Cell Lung Carcinoma (KEYNOTE 001)
| Verified date | November 2019 |
| Source | Merck Sharp & Dohme Corp. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The present study has 5 parts. In Parts A and A1, the dose of intravenous (IV) pembrolizumab (MK-3475) will be escalated from 1 to 10 mg/kg to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for participants with a histologically- or cytologically-confirmed diagnosis of any type of carcinoma or melanoma (MEL) by evaluating the Dose Limiting Toxicities (DLTs). Following completion of the dose escalation, additional patients will be enrolled in Part A2 to further define pharmacokinetic characteristics. Part B of the study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL and compare every 2 week dosing (Q2W) to every 3 week dosing (Q3W). Part C of the study will investigate the safety, tolerability, and efficacy of pembrolizumab administered at 10 mg/kg Q3W in participants with non-small cell lung carcinoma (NSCLC) that is locally advanced or metastatic. Part D of the study will investigate the low and high doses of study drug identified in Parts A and B (2 mg/kg and 10 mg/kg) administered Q3W in participants with advanced or metastatic MEL. Part E (closed with Amendment 7) was planned to investigate low, medium, and high doses of pembrolizumab in combination with standard chemotherapy in participants with locally advanced or metastatic NSCLC. Part F will investigate low and high doses of pembrolizumab (2 mg/kg and 10 mg/kg) administered Q2W or Q3W in treatment-naive and previously-treated participants with NSCLC with programmed cell death 1 ligand (PD-L1) gene expression. The primary hypotheses are the following: that pembrolizumab will have acceptable safety and tolerability; that pembrolizumab will show a clinically meaningful response rate (RR) or disease-control rate (DCR) in participants with melanoma (ipilimumab-refractory or not) and NSCLC, and that pembrolizumab will show a more clinically meaningful RR in participants with either cancer whose tumors express PD-L1.
| Status | Completed |
| Enrollment | 1260 |
| Est. completion date | December 11, 2018 |
| Est. primary completion date | November 5, 2018 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria - In Part A: Histological or cytological diagnosis of MEL or any type of carcinoma, progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy. In Parts B and D of the study, histological or cytological diagnoses of metastatic MEL with progressive locally advanced or metastatic disease. In Parts C and F, histological or cytological diagnosis of NSCLC. In Part F1, participants with Stage IV NSCLC without prior systemic therapy may be eligible. - Failure of established standard medical anti-cancer therapies for a given tumor type or intolerance to such therapy. - In Parts B, C, D, or F of the study, MEL or NSCLC must be measurable by imaging. - In Part F of the study, NSCLC with PD-L1 gene expression. - Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. - Adequate organ function. - Female participants of childbearing potential should have a negative urine or serum pregnancy test prior to receiving study medication - Female participants of childbearing potential must be willing to use adequate contraception from study start, through the course of the study, and for 120 days after the last dose of study medication - Male participants of childbearing potential must agree to use adequate contraception from the first dose of study medication through 120 days after the last dose of study medication Exclusion Criteria - Chemotherapy, radioactive, or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the adverse events caused by therapy administered more than 4 weeks prior to first dose. - Participation in a study of an investigational agent or using an investigational device within 30 days of administration of pembrolizumab, with the exception of participants in the follow-up phase. - Other form(s) of antineoplastic therapy anticipated during the period of the study. - History of non-infectious pneumonitis requiring treatment with steroids, or has a history of interstitial lung disease. - Medical condition that requires chronic systemic steroid therapy, or on any other form of immunosuppressive medication, excepting use of inhaled steroids. - Risk factors for bowel obstruction or bowel perforation (including a history of acute diverticulitis, intra-abdominal abscess, abdominal carcinomatosis). - History of a hematologic malignancy, malignant primary brain tumor, malignant sarcoma, or another malignant primary solid tumor, unless no evidence of that disease for 5 years. - Active central nervous system (CNS) metastases and/or carcinomatous meningitis. - Previous severe hypersensitivity reaction to another monoclonal antibody (mAb). - Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents, except vitiligo or resolved childhood asthma/atopy. - Prior therapy with another anti-programmed cell death (PD)-1 agent or previously enrolled in any pembrolizumab trial. - Active infection requiring therapy. - Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface Antigen [HBsAg] reactive), or Hepatitis C virus (Hepatitis C Virus Ribonucleic Acid [HCV RNA] (qualitative) is detected). - Regular use of illicit drugs or a recent history (within the last year) of substance abuse (including alcohol). - Symptomatic ascites or pleural effusion. - Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study. |
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme Corp. |
Chatterjee M, Turner DC, Felip E, Lena H, Cappuzzo F, Horn L, Garon EB, Hui R, Arkenau HT, Gubens MA, Hellmann MD, Dong D, Li C, Mayawala K, Freshwater T, Ahamadi M, Stone J, Lubiniecki GM, Zhang J, Im E, De Alwis DP, Kondic AG, Fløtten Ø. Systematic eval — View Citation
Patnaik A, Kang SP, Rasco D, Papadopoulos KP, Elassaiss-Schaap J, Beeram M, Drengler R, Chen C, Smith L, Espino G, Gergich K, Delgado L, Daud A, Lindia JA, Li XN, Pierce RH, Yearley JH, Wu D, Laterza O, Lehnert M, Iannone R, Tolcher AW. Phase I Study of P — View Citation
Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, Weber JS, Joshua AM, Hwu WJ, Gangadhar TC, Patnaik A, Dronca R, Zarour H, Joseph RW, Boasberg P, Chmielowski B, Mateus C, Postow MA, Gergich K, Elassaiss-Schaap J, Li XN, Iannone R, Ebbinghaus SW — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0) in Participants With Solid Tumors (Parts A and A1) | DLTs were assessed according to NCI-CTCAE v.4.0 during the first cycle (28 days) and were defined as occurrence of any of the following toxicities if judged by the investigator to be possibly, probably or definitely related to study drug administration: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting =14 days; Gr 3 nonhematologic toxicity lasting >3 days despite optimal supportive care; any Grade 3 non-hematologic laboratory value if medical intervention was required to treat the participant, the abnormality led to hospitalization, or the abnormality persisted for >1 week; Gr 3 or 4 febrile neutropenia; thrombocytopenia <25,000 cells/mm^3 (if associated with a bleeding event requiring an elective platelet transfusion, or a life-threatening bleeding event which resulted in urgent intervention and admission to an Intensive Care Unit); or Gr 5 toxicity. The number of participants in Part A and Part A1 with a DLT were reported by pembrolizumab dose received. | Up to 28 days in Cycle 1 | |
| Primary | Number of Participants Who Experienced an Adverse Event (AE) | An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who experienced an AE was reported for each arm. | Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018) | |
| Primary | Overall Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Integrated Radiology and Oncology (IRO): Melanoma Participants (Parts B Plus D) | ORR was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by IRO was reported as the ORR for each melanoma dose arm (Parts B plus D). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) | |
| Primary | ORR According to RECIST 1.1 as Assessed by Independent Review Committee (IRC): Non-Small Cell Lung Cancer (NSCLC) Participants (Parts C Plus F) | ORR was defined as the percentage of participants in the analysis population who had a confirmed CR (disappearance of all lesions) or PR (at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by IRC was reported as the ORR for each NSCLC dose arm (Parts C plus F). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | ORR According to Immune-related Response Criteria (irRC) as Assessed by Investigator in Melanoma Participants (Parts B Plus D) | ORR was defined as the percentage of participants in the analysis population who had a confirmed immune-related Complete Response (irCR: complete disappearance of all tumor lesions whether measurable or not, and no new lesions) or immune-related Partial Response (irPR: decrease in sum of the products of the two largest perpendicular diameters (SPD) of =50% by a consecutive assessment =4 weeks after first documentation) according to irRC. The percentage of participants who experienced a confirmed irCR or irPR according to irRC as assessed by the investigator was reported as the ORR for each melanoma dose arm (Parts B plus D). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | ORR According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F) | ORR was defined as the percentage of participants in the analysis population who had a confirmed irCR (complete disappearance of all tumor lesions whether measurable or not, and no new lesions) or irPR (decrease in sum of the products of the two largest perpendicular diameters (SPD) of =50% by a consecutive assessment =4 weeks after first documentation) according to irRC. The percentage of participants who experienced a confirmed irCR or irPR according to irRC as assessed by the investigator was reported as the ORR for each NSCLC dose arm (Parts C plus F). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | Area Under the Concentration-Time Curve of Pembrolizumab From Time 0 to Day 28 (AUC 0-28) in Solid Tumor Participants (Parts A and A1) | Blood samples were collected at specified intervals for the determination of AUC0-28. AUC0-28 was defined as the area under the concentration-time curve of pembrolizumab from time zero to Day 28. AUC0-28 was based on noncompartmental analysis and reported for participants in Parts A and A1. | Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days) | |
| Secondary | Area Under the Concentration-Time Curve of Pembrolizumab From Time 0 to Infinity (AUC 0-inf) in Solid Tumor Participants (Parts A and A1) | Blood samples were collected at specified intervals for the determination of AUC0-inf. AUC0-inf was defined as the area under the concentration-time curve of pembrolizumab from time zero to infinity. AUC0-inf was based on noncompartmental analysis and reported for participants in Parts A and A1. | Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days) | |
| Secondary | Maximum Concentration (Cmax) of Pembrolizumab in Solid Tumor Participants (Parts A and A1) | Blood samples were collected at specified intervals for the determination of Cmax. Cmax was defined as the maximum concentration of pembrolizumab reached. Cmax was based on noncompartmental analysis and reported for participants in Parts A and A1. | Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days) | |
| Secondary | Time to Maximum Concentration (Tmax) of Pembrolizumab in Solid Tumor Participants (Parts A and A1) | Blood samples were collected at specified intervals for the determination of Tmax. Tmax was defined as time to the maximum concentration of pembrolizumab reached. Tmax was based on noncompartmental analysis and reported for participants in Parts A and A1. | Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days) | |
| Secondary | Terminal Half-Life (t ½) of Pembrolizumab in Solid Tumor Participants (Parts A and A1) | Blood samples were collected at specified intervals for the determination of t½. t½ was defined as the time required to divide the pembrolizumab plasma concentration by two after reaching pseudo-equilibrium, following a single dose of pembrolizumab. t½ was based on noncompartmental analysis and reported for participants in Parts A and A1. | Cycle 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours and Days 8, 15, and 22 (Cycle 1 = 28 days) | |
| Secondary | Area Under the Concentration-Time Curve of Pembrolizumab From Time 0 to Day 21 (AUC 0-21) in Solid Tumor Participants (Part A2) | Blood samples were collected at specified intervals for the determination of AUC0-21. AUC0-21 was defined as the area under the concentration-time curve of pembrolizumab from time zero to Study Day 21. AUC0-21 was based on noncompartmental analysis and reported for participants in Part A2. | Cycle 1: Day 1: Pre-dose, post-dose at 0.5, 6, 24, and 48 hours; Day 5, Day 8: pre- and post-dose; Day 15 (Cycle = 21 days) | |
| Secondary | Area Under the Concentration-Time Curve of Pembrolizumab From Day 21 to Day 42 (AUC21-42) in Solid Tumor Participants (Part A2) | Blood samples were collected at specified intervals for the determination of AUC21-42. AUC21-42 was defined as the area under the concentration-time curve of pembrolizumab from Study Day 21 (end of Cycle 1) through Study Day 42 (end of Cycle 2). AUC21-42 was based on noncompartmental analysis and reported for participants in Part A2. | Cycle 1: Day 21; Cycle 2: Day 1: Pre-dose, post-dose at 0.5 and 24 hours, Day 3, Day 8, Day 15 (Cycle = 21 days) | |
| Secondary | Lowest Plasma Concentration (Ctrough) of Pembrolizumab in Solid Tumor Participants (Parts A, A1, and A2) | Pre-dose samples were collected 24 hours before infusion of pembrolizumab at specified intervals for the determination of Ctrough. Ctrough was defined as the lowest concentration of pembrolizumab reached before the next dose was administered. Ctrough was reported for each Part A arm according to cycle and nominal time after first dose (Day). Results for each cycle reported for arms with N>1 at that timepoint. Ctrough data for melanoma (Parts B and D) and NSCLC (Parts C and F) participants are presented separately and are not included here. | Parts A and A1: pre-dose at Cycles 2, 4, 6, 8, 10, 12, 14 (cycle=14 days); A2 Cohorts: pre-dose at Cycles 2, 3, 5, 7, 9, 11 (cycle=21 days) | |
| Secondary | Ctrough of Pembrolizumab in Melanoma Participants (Parts B and D) | Pre-dose samples were collected 24 hours before infusion of pembrolizumab at specified intervals for the determination of Ctrough. Ctrough was defined as the lowest concentration of pembrolizumab reached before the next dose was administered. For the purposes of the Ctrough analysis, samples were collected and analyzed separately for each Part B and D enrolment cohort, and Ctrough was reported for each cohort according to cycle and nominal time after first dose (Day). Results for each cycle reported for arms with N>1 at that timepoint. Ctrough data for solid tumor (Part A) and NSCLC (Parts C and F) participants are presented separately and are not included here. | Part B arms treated every 3 weeks: pre-dose at Cycles 2,5,9,13,17,25,33 (cycle=21 days); Part B treated every 2 weeks: pre-dose at Cycles 2,3,7,13,19,25,31,37 (cycle=14 days); Part D: pre-dose at Cycles 2,3,6,8,12,16,24,32 (cycle=21 days) | |
| Secondary | Ctrough of Pembrolizumab in NSCLC Participants (Parts C and F) | Pre-dose samples were collected 24 hours before infusion of pembrolizumab at specified intervals for the determination of Ctrough. Ctrough was defined as the lowest concentration reached by pembrolizumab before the next dose was administered. For the purposes of the Ctrough analysis, samples were collected and analyzed separately for each Part C and F enrolment cohort, and Ctrough was reported for each cohort according to cycle and nominal time after first dose (Day). Results for each cycle reported for arms with N>1 at that timepoint. Ctrough data for solid tumor (Part A) and melanoma (Parts B and D) participants are presented separately and are not included here. | Part C: pre-dose at Cycles 2,5,9,13,17,21 (cycle=21 days); Part F treated every 3 weeks: pre-dose at Cycles 2,3,6,8,12,14,16,24,32 (cycle=21 days); Part F treated every 2 weeks: pre-dose at Cycles 2,3,6,7,8,9,12,16,18,24,32,36,40,48 (cycle=14 days) | |
| Secondary | Maximum Change From Baseline (CFB) in Tumor Size Assessed by IRC Per RECIST 1.1 According to Programmed Death-Ligand 1 (PD-L1) Immunohistochemical (IHC) Expression Status in Ipilimumab (Ipi)-Exposed and Ipi-Naive Melanoma Participants (Parts B Plus D) | The percent change from baseline in tumor size based on IRC per RECIST 1.1 was reported according to PD-L1 status in Ipi-Exposed and Ipi-Naïve melanoma participants. Tumor PD-L1 status was measured by the tumor proportion score (TPS), which was the percentage of tumor cells identified using IHC analysis that expressed PD-L1. Tumors with =1% positive staining for PD-L1 were considered positive. Maximum tumor change was defined as the percent change of the participant's smallest post-baseline tumor size from the baseline. The number of participants in a percent change from baseline range was reported categorically according to PD-L1 status (PD-L1-Positive, PD-L1 Negative, PD-L1 Status Unknown). Negative percent change from baseline values indicate tumor size reduction, with the greatest reduction possible indicated as "= -30%". As specified by the protocol, this analysis of melanoma participants was performed according to ipilimumab exposure (Ipi-Exposed and Ipi-Naïve). | Baseline, last available tumor assessment (up to approximately 53 months through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | Maximum Change From Baseline (CFB) in Tumor Size Assessed by IRC Per RECIST 1.1 According to PD-L1 IHC Expression Status in Prior Treatment (TRT)-Naïve and Previously-Treated NSCLC Participants (Parts C Plus F) | Percent CFB in tumor size based on IRC per RECIST 1.1 was reported according to PD-L1 status in prior treatment-naïve and previously-treated NSCLC participants. Tumor PD-L1 status was measured by TPS, which was the percentage of tumor cells identified using IHC analysis that expressed PD-L1, as follows: TPS =50% =tumor strongly positive, TPS of 1%-49% =tumor weakly positive, TPS <1% =tumor considered negative, or TPS unknown. Maximum tumor change for a participant was defined as the percent change of the participant's smallest post-baseline tumor size from baseline. The number of participants in a percent CFB range was reported categorically according to PD-L1 status (TPS =50%, TPS = 1-49%, TPS <1%, TPS Unknown). Negative percent CFB values indicate tumor size reduction, with the greatest reduction possible indicated as "= -30%". As specified by the protocol, analysis of NSCLC participants was performed according to prior treatment exposure (Treatment Naive and Previously Treated). | Baseline, last available tumor assessment (up to approximately 53 months through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | Disease Control Rate (DCR) According to RECIST 1.1 as Assessed by IRO in Melanoma Participants (Parts B and D) | DCR was defined as the percentage of participants who had a CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD]). The percentage of participants who experienced a confirmed CR, PR, or SD according to RECIST 1.1 as assessed by IRO was reported as the DCR for each melanoma dose arm (Parts B plus D). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | Duration of Response (DOR) According to RECIST 1.1 as Assessed by IRO in Melanoma Participants (Parts B and D) | For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. DOR assessments were based on IRO with confirmation. The DOR according to RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported for each melanoma dose arm (Parts B plus D). | From time of first documented evidence of CR or PR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months) | |
| Secondary | Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by IRO in Melanoma Participants (Parts B Plus D) | PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. PFS according to RECIST 1.1 as assessed by IRO was reported for each melanoma dose arm (Parts B plus D). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | Overall Survival (OS) in Melanoma Participants (Parts B Plus D) | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. OS was reported for each melanoma dose arm (Parts B plus D). | Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018) | |
| Secondary | DCR According to irRC as Assessed by Investigator in Melanoma Participants (Parts B Plus D) | DCR according to irRC was defined as the percentage of participants who had a irCR (complete disappearance of all tumor lesions whether measurable or not, and no new lesions), irPR (decrease in SPD of =50% by a consecutive assessment =4 weeks after first documentation), or SD (neither sufficient shrinkage to qualify for irPR nor sufficient increase to qualify for PD [at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented]). The percentage of participants who experienced a confirmed CR, PR, or SD according to irRC as assessed by the investigator was reported as the DCR for each melanoma dose arm (Parts B plus D). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | DOR According to irRC as Assessed by Investigator in Melanoma Participants (Parts B Plus D) | For participants who demonstrated a confirmed irCR (complete disappearance of all tumor lesions whether measurable or not, and no new lesions) or irPR (decrease in SPD of =50% by a consecutive assessment =4 weeks after first documentation) according to irRC, DOR was defined as the time from first documented evidence of an irCR or irPR until PD or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. According to irRC, PD was defined as at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented. The DOR according to irRC as assessed by the investigator for all participants who experienced a confirmed irCR or irPR was reported for each melanoma dose arm (Parts B plus D). | From time of first documented evidence of iCR or iPR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months) | |
| Secondary | PFS According to irRC as Assessed by Investigator in Melanoma Participants (Parts B Plus D) | PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. According to irRC, PD was defined as at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented. PFS according to irRC as assessed by the investigator was reported for each melanoma dose arm (Parts B plus D). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | DCR According to RECIST 1.1 as Assessed by IRC in NSCLC Participants (Parts C Plus F) | DCR was defined as the percentage of participants who had a CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD]). The percentage of participants who experienced a confirmed CR, PR, or SD according to RECIST 1.1 as assessed by IRC was reported as the DCR for each NSCLC dose arm (Parts C plus F). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | DOR According to RECIST 1.1 as Assessed by IRC in NSCLC Participants (Parts C Plus F) | For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. DOR assessments were based on IRC with confirmation. The DOR according to RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported for each NSCLC dose arm (Parts C plus F). | From time of first documented evidence of CR or PR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months) | |
| Secondary | PFS According to RECIST 1.1 as Assessed by IRC in NSCLC Participants (Parts C Plus F) | PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of =5 mm. The appearance of one or more new lesions was also considered PD. PFS according to RECIST 1.1 as assessed by IRC was reported for each NSCLC dose arm (Parts C plus F). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | OS in NSCLC Participants (Parts C Plus F) | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. OS was reported for each NSCLC dose arm (Parts C plus F). | Up to approximately 91 months (through Final Database cut-off date of 05-Nov-2018) | |
| Secondary | DCR According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F) | DCR according to irRC was defined as the percentage of participants who had a irCR (complete disappearance of all tumor lesions whether measurable or not, and no new lesions), irPR (decrease in SPD of =50% by a consecutive assessment =4 weeks after first documentation), or SD (neither sufficient shrinkage to qualify for irPR nor sufficient increase to qualify for PD [at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented]). The percentage of participants who experienced a confirmed CR, PR, or SD according to irRC as assessed by the investigator was reported as the DCR for each NSCLC dose arm (Parts C plus F). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) | |
| Secondary | DOR According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F) | For participants who demonstrated a confirmed irCR (complete disappearance of all tumor lesions whether measurable or not, and no new lesions) or irPR (decrease in SPD of =50% by a consecutive assessment =4 weeks after first documentation) according to irRC, DOR was defined as the time from first documented evidence of an irCR or irPR until PD or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. According to irRC, PD was defined as at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented. The DOR according to irRC as assessed by the investigator for all participants who experienced a confirmed irCR or irPR was reported for each NSCLC dose arm (Parts C plus F). | From time of first documented evidence of iCR or iPR through Interim Database cut-off date of 18-Sep-2015 (Up to approximately 53 months) | |
| Secondary | PFS According to irRC as Assessed by Investigator in NSCLC Participants (Parts C Plus F) | PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. According to irRC, PD was defined as at least a 25% increase in SPD relative to nadir (minimum recorded tumor burden) with confirmation by a repeat, consecutive assessment no less than 4 weeks from the data first documented. PFS according to irRC as assessed by the investigator was reported for each NSCLC dose arm (Parts C plus F). | Up to approximately 53 months (through Interim Database cut-off date of 18-Sep-2015) |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02937116 -
First in Human Study of IBI308 in Chinese Subjects With Advanced Solid Tumors
|
Phase 1 |