| Primary | Dose-Escalation Phase: Number of Participants With Dose-Limiting Toxicity (DLT) | DLTs were defined as any of the following: i) Any treatment-emergent Grade greater than or equal to (≥) 3 toxicity that was considered related to either PEGPH20 or pembrolizumab or the combination of PEGPH20 and pembrolizumab (nausea, vomiting, MSEs, and diarrhea were considered DLTs only if they reached Grade ≥ 3 despite adequate supportive care measures); ii) Grade 3 musculoskeletal events (MSEs) were considered DLTs only if they did not reduce to Grade ≤ 2 within 48 hours despite therapeutic intervention; iii) Hypersensitivity/infusion reactions related to PEGPH20 or pembrolizumab dosing were not considered DLTs (hypersensitivity reactions were generally not related to the dose level of a drug since they could occur even upon a low level of exposure). | DLT evaluable population included all participants enrolled in dose escalation part who received at least 1 of the 3 full planned doses of PEGPH20 and 1 complete dose of pembrolizumab in Cycle 1 and had been followed for the first 21 days of treatment or had experienced a DLT during the initial 21 days (Cycle 1) of the study. | Posted | | Count of Participants | | Participants | | Cycle 1 (21 days) | | | | ID | Title | Description |
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| OG000 | Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 1.6 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks). | | OG001 | Dose Escalation (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks). | | OG002 | Dose Escalation (NSCLC): PEGPH20 1.6 µg/kg + Pembrolizumab | Participants with relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 1.6 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 27 weeks). | | OG003 | Dose Escalation (NSCLC): PEGPH20 2.2 µg/kg + Pembrolizumab | Participants with relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 27 weeks). |
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| Primary | Dose-Escalation Phase: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With Pembrolizumab | MTD of PEGPEM combination (PEGPH20 + Pembrolizumab) was defined as the highest dose level at which no more than 1 of 6 evaluable participants had experienced a DLT in the first 3 weeks of treatment. DLT was defined as any of the following: i) Any treatment-emergent Grade greater than or equal to (≥) 3 toxicity that was considered related to either PEGPH20 or pembrolizumab or the combination of PEGPH20 and pembrolizumab (nausea, vomiting, MSEs, and diarrhea were considered DLTs only if they reached Grade ≥ 3 despite adequate supportive care measures); ii) Grade 3 musculoskeletal events (MSEs) were considered DLTs only if they did not reduce to Grade ≤ 2 within 48 hours despite therapeutic intervention; iii) Hypersensitivity/infusion reactions related to PEGPH20 or pembrolizumab dosing were not considered DLTs (hypersensitivity reactions were generally not related to the dose level of a drug since they could occur even upon a low level of exposure). | After 9 participants enrolled in "Dose Escalation: PEGPH20 2.2 µg/kg + Pembrolizumab" group with only 1 DLT, the Sponsor decided to stop further dose escalation beyond 2.2 μg/kg, hence MTD was not established. | Posted | | | | | | Cycle 1 (21 days) | | | | ID | Title | Description |
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| OG000 | Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 1.6 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks). |
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| Primary | Dose Escalation Phase: Recommended Phase 2 Dose (RP2D) of PEGPH20 in Combination With Pembrolizumab | The RP2D was determined based on the overall safety profile of the participants enrolled during the dose-escalation part of the study. | DLT evaluable population included all participants enrolled in dose escalation part who received at least 1 of the 3 full planned doses of PEGPH20 and 1 complete dose of pembrolizumab in Cycle 1 and had been followed for the first 21 days of treatment or had experienced a DLT during the initial 21 days (Cycle 1) of the study. | Posted | | Number | | µg/kg | | Cycle 1 (21 days) | | | | ID | Title | Description |
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| OG000 | Dose Escalation Phase: All Participants (GAC and NSCLC) | Participants with relapsed/refractory locally advanced or metastatic GAC or Stage IIIB or IV NSCLC received PEGPH20 1.6 µg/kg or 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks for GAC, and 27 weeks for NSCLC). |
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| Primary | Dose Expansion Phase: Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by Investigator Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | ORR was defined as percentage of participants who achieved either a complete response (CR) or partial response (PR), as assessed by investigator based on RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | Tumor response evaluable population included all hyaluronan- high (HA-high) participants who received at least 1 dose of the RP2D of PEGPH20 and at least 1 dose of pembrolizumab; and who had at least one post-baseline tumor assessment on or post Cycle 2. | Posted | | Number | 80% Confidence Interval | percentage of participants | | Cycle 1 Day 1 of dose-expansion phase until death, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC) | | | | ID | Title | Description |
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| OG000 | Dose Expansion (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle and pembrolizumab 200 mg on Day 1 of each cycle, 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks). |
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| Secondary | Dose-Escalation Phase: ORR: Percentage of Participants With Objective Response, as Assessed by Investigator Based on RECIST Version 1.1 | ORR was defined as percentage of participants who achieved either a CR or PR, as assessed by investigator based on RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | Tumor response evaluable population included all HA-high participants who received at least 1 dose of the RP2D of PEGPH20 and at least 1 dose of pembrolizumab; and who had at least one post-baseline tumor assessment on or post Cycle 2. | Posted | | Number | 80% Confidence Interval | percentage of participants | | Cycle 1 Day 1 of dose-escalation phase until death, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks for GAC, and 27 weeks for NSCLC) | | | | ID | Title | Description |
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| OG000 | Dose Escalation (GAC): PEGPH20 1.6 or 2.2 µg/kg+Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 1.6 µg/kg or 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks). | |
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| Secondary | Dose-Escalation and Expansion Phase: Duration of Response (DOR), as Assessed by Investigator Based on RECIST v1.1 | DOR was defined as the time from the date on which objective response (CR or PR) was first determined until the first date on which radiographic disease progression was determined. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study thus far, the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. DOR was analyzed using Kaplan-Meier methods. | Tumor response evaluable population included all HA-high participants who received at least 1 dose of the RP2D of PEGPH20 and at least 1 dose of pembrolizumab; and who had at least one post-baseline tumor assessment on or post Cycle 2. 'Overall number of participants analyzed'=participants with a confirmed objective response. | Posted | | Median | 80% Confidence Interval | months | | From date of first objective response (CR or PR) until date of first radiographic disease progression (maximum exposure: 46 weeks for GAC, and 27 weeks for NSCLC in dose-escalation; 60 weeks for GAC, and 46 weeks for NSCLC in dose-expansion) | | | | ID | Title | Description |
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| OG000 | Dose Escalation (GAC): PEGPH20 1.6 or 2.2 µg/kg+Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 1.6 µg/kg or 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks). |
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| Secondary | Dose-Escalation and Expansion Phase: Disease Control Rate (DCR), as Assessed by Investigator Based on RECIST v1.1: Percentage of Participants Who Achieved CR, PR or Stable Disease (SD) | DCR was defined as percentage of participants who achieved CR, PR, or stable disease (SD). CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study thus far, the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. | Tumor response evaluable population included all HA-high participants who received at least 1 dose of the RP2D of PEGPH20 and at least 1 dose of pembrolizumab; and who had at least one post-baseline tumor assessment on or post Cycle 2. | Posted | | Number | 80% Confidence Interval | percentage of participants | | From first dose until first occurrence of CR, PR or SD (maximum exposure: 46 weeks for GAC, and 27 weeks for NSCLC in dose-escalation phase; maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC in dose-expansion phase) | | | | ID | Title | Description |
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| OG000 | Dose Escalation (GAC): PEGPH20 1.6 or 2.2 µg/kg+Pembrolizumab | |
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| Secondary | Dose-Escalation and Expansion Phase: Progression-Free Survival (PFS), as Assessed by Investigator Based on RECIST v1.1 | PFS was defined as the time from first dose date until the first occurrence of either radiographic or clinical disease progression as determined by the Investigator or death from any cause before discontinuation from treatment. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study thus far, the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. PFS was analyzed using Kaplan-Meier methods. | Efficacy evaluable population included all HA-high participants who received at least 1 dose of the RP2D of PEGPH20 and at least 1 dose of pembrolizumab. | Posted | | Median | 80% Confidence Interval | months | | From first dose until first occurrence of either radiographic or clinical disease progression or death (maximum exposure: 46 weeks for GAC, and 27 weeks for NSCLC in dose-escalation; 60 weeks for GAC, and 46 weeks for NSCLC in dose-expansion) | | | | ID | Title | Description |
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| OG000 | Dose Escalation (GAC): PEGPH20 1.6 or 2.2 µg/kg+Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 1.6 µg/kg or 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks). |
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| Secondary | Dose-Escalation and Expansion Phase: Overall Survival | Overall survival was defined as the time from first dose date until death from any cause. Overall survival was analyzed using Kaplan-Meier methods. | Efficacy evaluable population included all HA-high participants who received at least 1 dose of the RP2D of PEGPH20 and at least 1 dose of pembrolizumab. | Posted | | Median | 80% Confidence Interval | months | | From first dose until death from any cause (maximum exposure: 46 weeks for GAC, and 27 weeks for NSCLC in dose-escalation phase; maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC in dose-expansion phase) | | | | ID | Title | Description |
|---|
| OG000 | Dose Escalation (GAC): PEGPH20 1.6 or 2.2 µg/kg+Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 1.6 µg/kg or 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks). | | OG001 | Dose Escalation(NSCLC): PEGPH20 1.6 or 2.2 µg/kg+Pembrolizumab | Participants with relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 1.6 µg/kg or 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 27 weeks). |
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| Secondary | Dose Expansion Phase: Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by Investigator Based on Immune-Response Related Criteria (irRC) | ORR was defined as percentage of participants who achieved either CR or PR, as assessed by investigator based on irRC. CR was defined as disappearance of all lesions including non-index lesions and new non-measurable lesions, lymph nodes must be <10 mm in short axis). PR was defined as at least a 30% decrease in tumor burden from baseline. | Tumor response evaluable population included all HA-high participants who received at least 1 dose of the RP2D of PEGPH20 and at least 1 dose of pembrolizumab; and who had at least one post-baseline tumor assessment on or post Cycle 2. | Posted | | Number | 80% Confidence Interval | percentage of participants | | Cycle 1 Day 1 of dose-expansion phase until death, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC) | | | | ID | Title | Description |
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| OG000 | Dose Expansion (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle and pembrolizumab 200 mg on Day 1 of each cycle, 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks). | | OG001 | Dose Expansion (NSCLC): PEGPH20 2.2 µg/kg + Pembrolizumab |
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| Secondary | Dose- Expansion Phase: DOR, as Assessed by Investigator Based on irRC | DOR was defined as the time from the date on which objective response (CR or PR) was first determined until the first date on which radiographic disease progression was determined. CR was defined as disappearance of all lesions including non-index lesions and new non-measurable lesions, lymph nodes must be <10 mm in short axis). PR was defined as at least a 30% decrease in tumor burden from baseline. Disease progression was defined as at least a 20% increase in tumor burden from nadir. DOR was analyzed using Kaplan-Meier methods. | Tumor response evaluable population included all HA-high participants who received at least 1 dose of the RP2D of PEGPH20 and at least 1 dose of pembrolizumab; and who had at least one post-baseline tumor assessment on or post Cycle 2. 'Overall number of participants analyzed'=participants with a confirmed objective response. | Posted | | Median | 80% Confidence Interval | months | | From the date of first objective response (CR or PR) until the date of first radiographic disease progression (maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC) | | | | ID | Title | Description |
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| OG000 | Dose Expansion (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle and pembrolizumab 200 mg on Day 1 of each cycle, 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks). | |
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| Secondary | Dose- Expansion Phase: DCR, as Assessed by Investigator Based on irRC: Percentage of Participants Who Achieved CR, PR or SD | DCR was defined as percentage of participants who achieved CR, PR, or stable disease (SD). CR was defined as disappearance of all lesions including non-index lesions and new non-measurable lesions, lymph nodes must be <10 mm in short axis). PR was defined as at least a 30% decrease in tumor burden from baseline. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in tumor burden from nadir. | Tumor response evaluable population included all HA-high participants who received at least 1 dose of the RP2D of PEGPH20 and at least 1 dose of pembrolizumab; and who had at least one post-baseline tumor assessment on or post Cycle 2. | Posted | | Number | 80% Confidence Interval | percentage of participants | | From first dose until first occurrence of CR, PR or SD (maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC) | | | | ID | Title | Description |
|---|
| OG000 | Dose Expansion (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle and pembrolizumab 200 mg on Day 1 of each cycle, 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks). | | OG001 | Dose Expansion (NSCLC): PEGPH20 2.2 µg/kg + Pembrolizumab |
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| Secondary | Dose- Expansion Phase: PFS, as Assessed by Investigator Based on irRC | PFS was defined as the time from first dose date until the first occurrence of either radiographic or clinical disease progression as determined by the Investigator or death from any cause before discontinuation from treatment. Disease progression was defined as at least a 20% increase in tumor burden from nadir. PFS was analyzed using Kaplan-Meier methods. | Efficacy evaluable population included all HA-high participants who received at least 1 dose of the RP2D of PEGPH20 and at least 1 dose of pembrolizumab. | Posted | | Median | 80% Confidence Interval | months | | From first dose until the first occurrence of either radiographic or clinical disease progression or death from any cause (maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC) | | | | ID | Title | Description |
|---|
| OG000 | Dose Expansion (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab | Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle and pembrolizumab 200 mg on Day 1 of each cycle, 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks). | | OG001 | Dose Expansion (NSCLC): PEGPH20 2.2 µg/kg + Pembrolizumab | Participants with relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle and pembrolizumab 200 mg on Day 1 of each cycle, 4-6 hours after the completion of PEGPH20 administration. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks). |
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| Secondary | Dose-Escalation and Expansion Phase: Maximum Observed Plasma Concentration (Cmax) of PEGPH20 | Pharmacokinetic (PK) parameters for PEGPH20 were calculated using noncompartmental methods and summarized using descriptive statistics by dose. | Evaluable PK population included participants with at least one PK parameter for PEGPH20 following dosing on Day 1 of Cycle 1. | Posted | | Geometric Mean | Geometric Coefficient of Variation | nanograms/milliliter (ng/mL) | | Pre PEGPH20 dose (within 2 hours [hrs] pre-dose); 0.25,1, 2-4, and 6-8 hrs post PEGPH20 dose at Cycle 1 Day 1 (cycle length = 21 days) | | | | ID | Title | Description |
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| OG000 | PEGPH20 1.6 μg/kg + Pembrolizumab 2 mg/kg | Participants with relapsed/refractory locally advanced or metastatic GAC or relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 1.6 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration in dose escalation phase of study. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks in participants with GAC and 27 weeks in participants with NSCLC). | | OG001 | PEGPH20 2.2 μg/kg + Pembrolizumab 2 mg/kg | Participants with relapsed/refractory locally advanced or metastatic GAC or relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration in dose escalation phase of study. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks in participants with GAC and 27 weeks in participants with NSCLC). |
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| Secondary | Dose-Escalation and Expansion Phase: Terminal Elimination Half-Life (t1/2) of PEGPH20 | PK parameters for PEGPH20 were calculated using noncompartmental methods and summarized using descriptive statistics by dose. | Evaluable PK population included participants with at least one PK parameter for PEGPH20 following dosing on Day 1 of Cycle 1. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. | Posted | | Mean | Standard Deviation | hours | | Pre PEGPH20 dose (within 2 hours [hrs] pre-dose); 0.25,1, 2-4, and 6-8 hrs post PEGPH20 dose at Cycle 1 Day 1 (cycle length = 21 days) | | | | ID | Title | Description |
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| OG000 | PEGPH20 1.6 μg/kg + Pembrolizumab 2 mg/kg | Participants with relapsed/refractory locally advanced or metastatic GAC or relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 1.6 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration in dose escalation phase of study. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks in participants with GAC and 27 weeks in participants with NSCLC). | | OG001 | PEGPH20 2.2 μg/kg + Pembrolizumab 2 mg/kg | Participants with relapsed/refractory locally advanced or metastatic GAC or relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration in dose escalation phase of study. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks in participants with GAC and 27 weeks in participants with NSCLC). |
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| Secondary | Dose-Escalation and Expansion Phase: Area Under the Plasma Concentration Vs. Time Curve From Time 0 to Last Quantifiable Concentration (AUClast) of PEGPH20 | PK parameters for PEGPH20 were calculated using noncompartmental methods and summarized using descriptive statistics by dose. | Evaluable PK population included participants with at least one PK parameter for PEGPH20 following dosing on Day 1 of Cycle 1. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | Pre PEGPH20 dose (within 2 hours [hrs] pre-dose); 0.25,1, 2-4, and 6-8 hrs post PEGPH20 dose at Cycle 1 Day 1 (cycle length = 21 days) | | | | ID | Title | Description |
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| OG000 | PEGPH20 1.6 μg/kg + Pembrolizumab 2 mg/kg | Participants with relapsed/refractory locally advanced or metastatic GAC or relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 1.6 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration in dose escalation phase of study. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks in participants with GAC and 27 weeks in participants with NSCLC). | | OG001 | PEGPH20 2.2 μg/kg + Pembrolizumab 2 mg/kg | Participants with relapsed/refractory locally advanced or metastatic GAC or relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration in dose escalation phase of study. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks in participants with GAC and 27 weeks in participants with NSCLC). |
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| Secondary | Dose-Escalation and Expansion Phase: Volume of Distribution (Vd) of PEGPH20 | PK parameters for PEGPH20 were calculated using noncompartmental methods and summarized using descriptive statistics by dose. | Vd could not be determined due to the AUC% extrapolation of greater than 20%. | Posted | | | | | | Pre PEGPH20 dose (within 2 hours [hrs] pre-dose); 0.25,1, 2-4, and 6-8 hrs post PEGPH20 dose at Cycle 1 Day 1 (cycle length = 21 days) | | | | ID | Title | Description |
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| OG000 | PEGPH20 1.6 μg/kg + Pembrolizumab 2 mg/kg | Participants with relapsed/refractory locally advanced or metastatic GAC or relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 1.6 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration in dose escalation phase of study. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks in participants with GAC and 27 weeks in participants with NSCLC). | | OG001 | PEGPH20 2.2 μg/kg + Pembrolizumab 2 mg/kg | Participants with relapsed/refractory locally advanced or metastatic GAC or relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration in dose escalation phase of study. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks in participants with GAC and 27 weeks in participants with NSCLC). |
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| Secondary | Dose-Escalation and Expansion Phase: Clearance (CL) of PEGPH20 | PK parameters for PEGPH20 were calculated using noncompartmental methods and summarized using descriptive statistics by dose. | CL could not be determined due to the AUC% extrapolation of greater than 20%. | Posted | | | | | | Pre PEGPH20 dose (within 2 hours [hrs] pre-dose); 0.25,1, 2-4, and 6-8 hrs post PEGPH20 dose at Cycle 1 Day 1 (cycle length = 21 days) | | | | ID | Title | Description |
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| OG000 | PEGPH20 1.6 μg/kg + Pembrolizumab 2 mg/kg | Participants with relapsed/refractory locally advanced or metastatic GAC or relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 1.6 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration in dose escalation phase of study. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks in participants with GAC and 27 weeks in participants with NSCLC). | | OG001 | PEGPH20 2.2 μg/kg + Pembrolizumab 2 mg/kg | Participants with relapsed/refractory locally advanced or metastatic GAC or relapsed/refractory Stage IIIB or IV NSCLC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration in dose escalation phase of study. Treatment was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks in participants with GAC and 27 weeks in participants with NSCLC). |
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| Secondary | Number of Participants With Adverse Events (AEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'. | Safety population included all enrolled participants in either the Dose Escalation or Dose Expansion portion of the study, who received at least 1 dose of any study medication (PEGPH20 or pembrolizumab). | Posted | | Count of Participants | | Participants | | Cycle 1 Day 1 up to 30 days after last dose of study drug (maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC) | | | | ID | Title | Description |
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| OG000 | GAC: PEGPH20 1.6 µg/kg/2.2 µg/kg + Pembrolizumab | Dose escalation part: Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 1.6 µg/kg or 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Dose expansion part: Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle and pembrolizumab 200 mg on Day 1 of each cycle, 4-6 hours after the completion of PEGPH20 administration. Treatment in both phases of the study was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks). |
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| Secondary | Dose-Expansion Phase: Number of Participants With Clinically Significant Abnormalities in Clinical Laboratory Parameters and Vital Signs | Clinical laboratory parameters included hematology (haemoglobin [Hb], hematocrit, red blood cell count, white blood cell count, neutrophils [ANC], lymphocytes, monocytes, eosinophils, basophils, granulocytes, mean corpuscular Hb, mean corpuscular volume, and platelet count) and blood chemistry (glucose, blood urea nitrogen [BUN], alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin, bilirubin, bicarbonate, calcium, chloride, magnesium, potassium, sodium, thyrotropin, thyroxin, triiodothyronine, alkaline phosphatase [ALP], electrolytes, and creatinine). Vital signs included measurement of blood pressure (systolic and diastolic), pulse, respiratory rate, and body temperature. Criteria for clinical significance were as per investigator's discretion. | Safety population included all enrolled participants in either the Dose Escalation or Dose Expansion portion of the study, who received at least 1 dose of any study medication (PEGPH20 or pembrolizumab). | Posted | | Count of Participants | | Participants | | Cycle 1 Day 1 up to 30 days after last dose of study drug (maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC) | | | | ID | Title | Description |
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| OG000 | GAC: PEGPH20 1.6 µg/kg/2.2 µg/kg + Pembrolizumab | Dose escalation part: Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 1.6 µg/kg or 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Dose expansion part: Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle and pembrolizumab 200 mg on Day 1 of each cycle, 4-6 hours after the completion of PEGPH20 administration. Treatment in both phases of the study was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks). |
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| Secondary | Dose-Expansion Phase: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) | ECGs including clinical significance was evaluated by the Investigator. Criteria for clinical significance were as per investigator's discretion. | Safety population included all enrolled participants in either the Dose Escalation or Dose Expansion portion of the study, who received at least 1 dose of any study medication (PEGPH20 or pembrolizumab). | Posted | | Count of Participants | | Participants | | Cycle 1 Day 1 up to 30 days after last dose of study drug (maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC) | | | | ID | Title | Description |
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| OG000 | GAC: PEGPH20 1.6 µg/kg/2.2 µg/kg + Pembrolizumab | Dose escalation part: Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 1.6 µg/kg or 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Dose expansion part: Participants with relapsed/refractory locally advanced or metastatic GAC received PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle and pembrolizumab 200 mg on Day 1 of each cycle, 4-6 hours after the completion of PEGPH20 administration. Treatment in both phases of the study was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks). | | OG001 | NSCLC: PEGPH20 1.6 µg/kg/2.2 µg/kg + Pembrolizumab |
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