Trial Outcomes & Findings for A Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) With Pembrolizumab in Participants With Selected Hyaluronan High Solid Tumors (NCT NCT02563548)

Last Updated: 2020-02-07

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

56 participants

Primary outcome timeframe

Cycle 1 (21 days)

Results posted on

2020-02-07

Participant Flow

The study was conducted in 2 parts: dose escalation and dose expansion. A total of 56 participants were enrolled (35 with gastric adenocarcinoma \[GAC\] and 21 with non-small cell lung cancer \[NSCLC\]).

14 participants (10 with GAC and 4 with NSCLC) were enrolled in dose escalation part. Due to evolving standard-of-care in the immuno-oncology treatment landscape, this study discontinued further enrollment on 31 May 2018. At the time of the early termination, 42 participants (25 with GAC and 17 with NSCLC) had been enrolled in dose expansion part.

Participant milestones

Participant milestones
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab Participants with relapsed/refractory locally advanced or metastatic GAC received PEGylated recombinant human hyaluronidase (PEGPH20) 1.6 micrograms/kilogram (µg/kg) on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 milligrams/kilogram (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).	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).	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).	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).	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).	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).
Dose Escalation (Up to 46 Weeks) STARTED	3	2	7	2	0	0
Dose Escalation (Up to 46 Weeks) Received at Least 1 Dose of Study Drug	3	2	7	2	0	0
Dose Escalation (Up to 46 Weeks) COMPLETED	0	0	0	0	0	0
Dose Escalation (Up to 46 Weeks) NOT COMPLETED	3	2	7	2	0	0
Dose Expansion (Up to 60 Weeks) STARTED	0	0	0	0	25	17
Dose Expansion (Up to 60 Weeks) Received at Least 1 Dose of Study Drug	0	0	0	0	24	17
Dose Expansion (Up to 60 Weeks) COMPLETED	0	0	0	0	0	0
Dose Expansion (Up to 60 Weeks) NOT COMPLETED	0	0	0	0	25	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab Participants with relapsed/refractory locally advanced or metastatic GAC received PEGylated recombinant human hyaluronidase (PEGPH20) 1.6 micrograms/kilogram (µg/kg) on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 milligrams/kilogram (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).	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).	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).	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).	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).	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).
Dose Escalation (Up to 46 Weeks) Adverse Event	2	0	0	1	0	0
Dose Escalation (Up to 46 Weeks) Radiological Progression	1	2	2	0	0	0
Dose Escalation (Up to 46 Weeks) Clinical Progression	0	0	3	0	0	0
Dose Escalation (Up to 46 Weeks) Withdrawal by Subject	0	0	2	1	0	0
Dose Expansion (Up to 60 Weeks) Adverse Event	0	0	0	0	1	8
Dose Expansion (Up to 60 Weeks) Radiological Progression	0	0	0	0	15	3
Dose Expansion (Up to 60 Weeks) Clinical Progression	0	0	0	0	6	0
Dose Expansion (Up to 60 Weeks) Withdrawal by Subject	0	0	0	0	2	1
Dose Expansion (Up to 60 Weeks) Investigator or Sponsor Decision	0	0	0	0	0	2
Dose Expansion (Up to 60 Weeks) Protocol Violation	0	0	0	0	0	2
Dose Expansion (Up to 60 Weeks) Increased brain lesions	0	0	0	0	0	1
Dose Expansion (Up to 60 Weeks) Enrolled but not treated	0	0	0	0	1	0

Baseline Characteristics

A Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) With Pembrolizumab in Participants With Selected Hyaluronan High Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GAC: PEGPH20 1.6 µg/kg/2.2 µg/kg + Pembrolizumab n=34 Participants 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).	NSCLC: PEGPH20 1.6 µg/kg/2.2 µg/kg + Pembrolizumab n=21 Participants Dose escalation part: 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. Dose expansion part: 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 in both phases of the study was continued until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks).	Total n=55 Participants Total of all reporting groups
Age, Continuous	62.3 years STANDARD_DEVIATION 8.89 • n=5 Participants	67.7 years STANDARD_DEVIATION 10.66 • n=7 Participants	64.4 years STANDARD_DEVIATION 9.87 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	11 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	10 Participants n=7 Participants	39 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=5 Participants	18 Participants n=7 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	17 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1 (21 days)

Population: 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.

Outcome measures

Outcome measures
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab n=2 Participants 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).	Dose Escalation (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab n=7 Participants 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).	Dose Escalation (NSCLC): PEGPH20 1.6 µg/kg + Pembrolizumab n=2 Participants 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).	Dose Escalation (NSCLC): PEGPH20 2.2 µg/kg + Pembrolizumab n=2 Participants 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).
Dose-Escalation Phase: Number of Participants With Dose-Limiting Toxicity (DLT)	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Cycle 1 (21 days)

Population: 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.

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).

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Cycle 1 (21 days)

The RP2D was determined based on the overall safety profile of the participants enrolled during the dose-escalation part of the study.

Outcome measures

Outcome measures
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab n=13 Participants 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).	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).	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).	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).
Dose Escalation Phase: Recommended Phase 2 Dose (RP2D) of PEGPH20 in Combination With Pembrolizumab	2.2 µg/kg	—	—	—

PRIMARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab n=21 Participants 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).	Dose Escalation (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab n=14 Participants 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).	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).	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).
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	9.5 percentage of participants Interval 2.6 to 23.4	28.6 percentage of participants Interval 13.1 to 49.2	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab n=8 Participants 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).	Dose Escalation (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab n=3 Participants 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).	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).	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).
Dose-Escalation Phase: ORR: Percentage of Participants With Objective Response, as Assessed by Investigator Based on RECIST Version 1.1	0 percentage of participants Interval 0.0 to 25.0	0 percentage of participants Interval 0.0 to 53.6	—	—

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	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).	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).	Dose Escalation (NSCLC): PEGPH20 1.6 µg/kg + Pembrolizumab n=2 Participants 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).	Dose Escalation (NSCLC): PEGPH20 2.2 µg/kg + Pembrolizumab n=4 Participants 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).
Dose-Escalation and Expansion Phase: Duration of Response (DOR), as Assessed by Investigator Based on RECIST v1.1	—	—	8.5 months Due to less number of participants with an event, upper and lower limit of 80% CI could not be calculated.	2.8 months Interval 1.3 to 2.8

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab n=8 Participants 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).	Dose Escalation (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab n=3 Participants 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).	Dose Escalation (NSCLC): PEGPH20 1.6 µg/kg + Pembrolizumab n=21 Participants 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).	Dose Escalation (NSCLC): PEGPH20 2.2 µg/kg + Pembrolizumab n=14 Participants 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).
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)	12.5 percentage of participants Interval 1.3 to 40.6	66.7 percentage of participants Interval 19.6 to 96.5	47.6 percentage of participants Interval 32.1 to 63.6	71.4 percentage of participants Interval 50.8 to 86.9

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab n=10 Participants 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).	Dose Escalation (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab n=4 Participants 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).	Dose Escalation (NSCLC): PEGPH20 1.6 µg/kg + Pembrolizumab n=24 Participants 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).	Dose Escalation (NSCLC): PEGPH20 2.2 µg/kg + Pembrolizumab n=17 Participants 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).
Dose-Escalation and Expansion Phase: Progression-Free Survival (PFS), as Assessed by Investigator Based on RECIST v1.1	1.2 months Interval 1.2 to 1.4	1.7 months Interval 0.9 to Due to less number of participants with an event, upper limit of 80% CI could not be calculated.	1.4 months Interval 1.2 to 1.4	4.2 months Interval 1.7 to 5.8

SECONDARY outcome

Timeframe: 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)

Population: 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.

Overall survival was defined as the time from first dose date until death from any cause. Overall survival was analyzed using Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab n=10 Participants 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).	Dose Escalation (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab n=4 Participants 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).	Dose Escalation (NSCLC): PEGPH20 1.6 µg/kg + Pembrolizumab n=24 Participants 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).	Dose Escalation (NSCLC): PEGPH20 2.2 µg/kg + Pembrolizumab n=17 Participants 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).
Dose-Escalation and Expansion Phase: Overall Survival	2.9 months Interval 1.8 to 7.5	4.7 months Interval 2.8 to Due to fewer number of participants with an event, upper limit of 80% CI could not be calculated.	4.4 months Interval 3.5 to 5.8	12.9 months Interval 5.1 to Due to fewer number of participants with an event, upper limit of 80% CI could not be calculated.

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab n=21 Participants 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).	Dose Escalation (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab n=14 Participants 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).	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).	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).
Dose Expansion Phase: Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by Investigator Based on Immune-Response Related Criteria (irRC)	9.5 percentage of participants Interval 2.6 to 23.4	28.6 percentage of participants Interval 13.1 to 49.2	—	—

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab n=2 Participants 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).	Dose Escalation (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab n=4 Participants 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).	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).	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).
Dose- Expansion Phase: DOR, as Assessed by Investigator Based on irRC	8.5 months Due to fewer number of participants with an event, upper and lower limit of 80% CI could not be calculated.	2.8 months Interval 1.3 to 2.8	—	—

SECONDARY outcome

Timeframe: From first dose until first occurrence of CR, PR or SD (maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC)

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.

Outcome measures

Outcome measures
Measure	Dose Escalation (GAC): PEGPH20 1.6 µg/kg + Pembrolizumab n=21 Participants 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).	Dose Escalation (GAC): PEGPH20 2.2 µg/kg + Pembrolizumab n=14 Participants 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).	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).	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).
Dose- Expansion Phase: DCR, as Assessed by Investigator Based on irRC: Percentage of Participants Who Achieved CR, PR or SD	47.6 percentage of participants Interval 32.1 to 63.6	78.6 percentage of participants Interval 58.3 to 91.9	—	—

SECONDARY outcome

Timeframe: 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)

Population: 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.