Trial Outcomes & Findings for Study of TSR-033 With an Anti-programmed Cell Death-1 Receptor (PD-1) in Participants With Advanced Solid Tumors (NCT NCT03250832)

Last Updated: 2024-04-11

Results Overview

Blood samples were collected for the analysis of clinical chemistry parameters and each parameter was graded according to national cancer institute (NCI)-common terminology criteria for adverse events (CTCAE) version 5.0. Grade 0: normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Data have been presented for the number of participants with clinical chemistry grade3 and 4 toxicities each parameter.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

111 participants

Primary outcome timeframe

Up to 51 months

Results posted on

2024-04-11

Participant Flow

The study was comprised of two parts. Part 1 was a dose escalation phase and consisted of two cohorts 1AB and 1C. Part 2 was Colorectal Cancer dose expansion phase and consisted of 3 cohorts 2A, 2B1 and 2B2.

Participant milestones

Participant milestones
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (720 mg) In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 2A - TSR-033 (720 mg) + Dostarlimab (1000 mg) Anti-programmed cell death-1 receptor (PD-1) naive participants with advanced or metastatic microsatellite stable colorectal cancer (MSS-CRC) that progressed following 2 or 3 prior lines of therapy received IV infusion of 720 mg TSR-033 once Q2W in combination with 1000 mg dostarlimab once every 6 weeks (Q6W).	Part 2B1 - TSR-033 (720 mg) + Dostarlimab (1000 mg) + Bev + mFOLFOX6 Anti-PD-1-naive participants with advanced or metastatic MSS-CRC following progression on frontline treatment with FOLFIRI (or variant), with or without biologics received IV infusion of 720 mg TSR-033 once (on day 3 of each cycle) Q2W in combination with 1000 mg dostarlimab once (on day 3 of each cycle) Q6W and mFOLFOX6 (on day 1 of each cycle) Q6W and 30-minute IV infusion of bevacizumab (bev) once (on day 1 of each cycle) Q6W. As a part of mFOLFOX6 regimen combination of 2-hour infusion of oxaliplatin with leucovorin and 2-4 minutes infusion of 5-Fluorouracil on day 1 along with continuous 46-hours infusion of 5-Fluorouracil on day 1 to day 3 were administered.	Part 2B2 - TSR-033 (720 mg) + Dostarlimab (1000 mg) + Bev +FOLFIRI Anti-PD-1-naive participants with advanced or metastatic MSS-CRC following progression on frontline treatment with FOLFOX (or variant), with or without biologics received IV infusion of 720 mg TSR-033 once (on day 3 of each cycle) Q2W in combination with 1000 mg dostarlimab once (on day 3 of each cycle) Q6W and FOLFIRI (on day 1 of each cycle) Q6W and 30-minute IV infusion of bevacizumab (bev) once (on day 1 of each cycle) Q6W. As a part of FOLFIRI regimen combination of 90 minutes infusion of Irinotecan with leucovorin with 2-4 minutes infusion of 5-Fluorouracil on day 1 and continuous 46-hours infusion of 5-Fluorouracil on day 1 to day 3 were administered.	PACT Phase - TSR-033 (720 mg) + Dostarlimab (1000 mg) Anti-programmed cell death-1 receptor (PD-1) naive participants with advanced or metastatic microsatellite stable colorectal cancer (MSS-CRC) that progressed following 2 or 3 prior lines of therapy received IV infusion of 720 mg TSR-033 once Q2W in combination with 1000 mg dostarlimab once every 6 weeks (Q6W).	PACT Phase - TSR-033 (720 mg) + Dostarlimab (1000 mg) + Bev +FOLFIRI Anti-PD-1-naive participants with advanced or metastatic MSS-CRC following progression on frontline treatment with FOLFOX (or variant), with or without biologics received IV infusion of 720 mg TSR-033 once (on day 3 of each cycle) Q2W in combination with 1000 mg dostarlimab once (on day 3 of each cycle) Q6W and FOLFIRI (on day 1 of each cycle) Q6W and 30-minute IV infusion of bevacizumab (bev) once (on day 1 of each cycle) Q6W. As a part of FOLFIRI regimen combination of 90 minutes infusion of Irinotecan with leucovorin with 2-4 minutes infusion of 5-Fluorouracil on day 1 and continuous 46-hours infusion of 5-Fluorouracil on day 1 to day 3 were administered.
Part 1 (Up to Approximately 51 Months) STARTED	3	10	11	10	5	7	6	0	0	0	0	0
Part 1 (Up to Approximately 51 Months) COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0
Part 1 (Up to Approximately 51 Months) NOT COMPLETED	3	10	11	10	5	7	6	0	0	0	0	0
Part 2A (Up to Approximately 30 Months) STARTED	0	0	0	0	0	0	0	34	0	0	0	0
Part 2A (Up to Approximately 30 Months) COMPLETED	0	0	0	0	0	0	0	1	0	0	0	0
Part 2A (Up to Approximately 30 Months) NOT COMPLETED	0	0	0	0	0	0	0	33	0	0	0	0
Part 2B (Up to Approximately 29 Months) STARTED	0	0	0	0	0	0	0	0	4	21	0	0
Part 2B (Up to Approximately 29 Months) COMPLETED	0	0	0	0	0	0	0	0	0	1	0	0
Part 2B (Up to Approximately 29 Months) NOT COMPLETED	0	0	0	0	0	0	0	0	4	20	0	0
PACT Phase (up to Approximately 36weeks) STARTED	0	0	0	0	0	0	0	0	0	0	1	1
PACT Phase (up to Approximately 36weeks) COMPLETED	0	0	0	0	0	0	0	0	0	0	1	0
PACT Phase (up to Approximately 36weeks) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (720 mg) In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 2A - TSR-033 (720 mg) + Dostarlimab (1000 mg) Anti-programmed cell death-1 receptor (PD-1) naive participants with advanced or metastatic microsatellite stable colorectal cancer (MSS-CRC) that progressed following 2 or 3 prior lines of therapy received IV infusion of 720 mg TSR-033 once Q2W in combination with 1000 mg dostarlimab once every 6 weeks (Q6W).	Part 2B1 - TSR-033 (720 mg) + Dostarlimab (1000 mg) + Bev + mFOLFOX6 Anti-PD-1-naive participants with advanced or metastatic MSS-CRC following progression on frontline treatment with FOLFIRI (or variant), with or without biologics received IV infusion of 720 mg TSR-033 once (on day 3 of each cycle) Q2W in combination with 1000 mg dostarlimab once (on day 3 of each cycle) Q6W and mFOLFOX6 (on day 1 of each cycle) Q6W and 30-minute IV infusion of bevacizumab (bev) once (on day 1 of each cycle) Q6W. As a part of mFOLFOX6 regimen combination of 2-hour infusion of oxaliplatin with leucovorin and 2-4 minutes infusion of 5-Fluorouracil on day 1 along with continuous 46-hours infusion of 5-Fluorouracil on day 1 to day 3 were administered.	Part 2B2 - TSR-033 (720 mg) + Dostarlimab (1000 mg) + Bev +FOLFIRI Anti-PD-1-naive participants with advanced or metastatic MSS-CRC following progression on frontline treatment with FOLFOX (or variant), with or without biologics received IV infusion of 720 mg TSR-033 once (on day 3 of each cycle) Q2W in combination with 1000 mg dostarlimab once (on day 3 of each cycle) Q6W and FOLFIRI (on day 1 of each cycle) Q6W and 30-minute IV infusion of bevacizumab (bev) once (on day 1 of each cycle) Q6W. As a part of FOLFIRI regimen combination of 90 minutes infusion of Irinotecan with leucovorin with 2-4 minutes infusion of 5-Fluorouracil on day 1 and continuous 46-hours infusion of 5-Fluorouracil on day 1 to day 3 were administered.	PACT Phase - TSR-033 (720 mg) + Dostarlimab (1000 mg) + Bev +FOLFIRI Anti-PD-1-naive participants with advanced or metastatic MSS-CRC following progression on frontline treatment with FOLFOX (or variant), with or without biologics received IV infusion of 720 mg TSR-033 once (on day 3 of each cycle) Q2W in combination with 1000 mg dostarlimab once (on day 3 of each cycle) Q6W and FOLFIRI (on day 1 of each cycle) Q6W and 30-minute IV infusion of bevacizumab (bev) once (on day 1 of each cycle) Q6W. As a part of FOLFIRI regimen combination of 90 minutes infusion of Irinotecan with leucovorin with 2-4 minutes infusion of 5-Fluorouracil on day 1 and continuous 46-hours infusion of 5-Fluorouracil on day 1 to day 3 were administered.
Part 1 (Up to Approximately 51 Months) Death	1	6	5	5	3	6	3	0	0	0	0
Part 1 (Up to Approximately 51 Months) Withdrawal by Subject	2	4	5	5	2	1	3	0	0	0	0
Part 1 (Up to Approximately 51 Months) Sponsor Decision	0	0	1	0	0	0	0	0	0	0	0
Part 2A (Up to Approximately 30 Months) Death	0	0	0	0	0	0	0	18	0	0	0
Part 2A (Up to Approximately 30 Months) Lost to Follow-up	0	0	0	0	0	0	0	3	0	0	0
Part 2A (Up to Approximately 30 Months) Withdrawal by Subject	0	0	0	0	0	0	0	8	0	0	0
Part 2A (Up to Approximately 30 Months) Sponsor Decision	0	0	0	0	0	0	0	3	0	0	0
Part 2A (Up to Approximately 30 Months) Other	0	0	0	0	0	0	0	1	0	0	0
Part 2B (Up to Approximately 29 Months) Death	0	0	0	0	0	0	0	0	1	7	0
Part 2B (Up to Approximately 29 Months) Withdrawal by Subject	0	0	0	0	0	0	0	0	2	7	0
Part 2B (Up to Approximately 29 Months) Sponsor Decision	0	0	0	0	0	0	0	0	1	6	0
PACT Phase (up to Approximately 36weeks) Lost to Follow-up	0	0	0	0	0	0	0	0	0	0	1

Baseline Characteristics

Study of TSR-033 With an Anti-programmed Cell Death-1 Receptor (PD-1) in Participants With Advanced Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=3 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) n=11 Participants In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (720 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) n=5 Participants Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) n=7 Participants Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) n=6 Participants Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 2A - TSR-033 (720 mg) + Dostarlimab (1000 mg) n=34 Participants Anti-programmed cell death-1 receptor (PD-1) naive participants with advanced or metastatic microsatellite stable colorectal cancer (MSS-CRC) that progressed following 2 or 3 prior lines of therapy received IV infusion of 720 mg TSR-033 once Q2W in combination with 1000 mg dostarlimab once every 6 weeks (Q6W).	Part 2B1 - TSR-033 (720 mg) + Dostarlimab (1000 mg) + Bev + mFOLFOX6 n=4 Participants Anti-PD-1-naive participants with advanced or metastatic MSS-CRC following progression on frontline treatment with FOLFIRI (or variant), with or without biologics received IV infusion of 720 mg TSR-033 once (on day 3 of each cycle) Q2W in combination with 1000 mg dostarlimab once (on day 3 of each cycle) Q6W and mFOLFOX6 (on day 1 of each cycle) Q6W and 30-minute IV infusion of bevacizumab (bev) once (on day 1 of each cycle) Q6W. As a part of mFOLFOX6 regimen combination of 2-hour infusion of oxaliplatin with leucovorin and 2-4 minutes infusion of 5-Fluorouracil on day 1 along with continuous 46-hours infusion of 5-Fluorouracil on day 1 to day 3 were administered.	Part 2B2 - TSR-033 (720 mg) + Dostarlimab (1000 mg) + Bev +FOLFIRI n=21 Participants Anti-PD-1-naive participants with advanced or metastatic MSS-CRC following progression on frontline treatment with FOLFOX (or variant), with or without biologics received IV infusion of 720 mg TSR-033 once (on day 3 of each cycle) Q2W in combination with 1000 mg dostarlimab once (on day 3 of each cycle) Q6W and FOLFIRI (on day 1 of each cycle) Q6W and 30-minute IV infusion of bevacizumab (bev) once (on day 1 of each cycle) Q6W. As a part of FOLFIRI regimen combination of 90 minutes infusion of Irinotecan with leucovorin with 2-4 minutes infusion of 5-Fluorouracil on day 1 and continuous 46-hours infusion of 5-Fluorouracil on day 1 to day 3 were administered.	Total n=111 Participants Total of all reporting groups
Age, Customized <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	0 Participants n=62 Participants	0 Participants n=95 Participants
Age, Customized 19 - 64 years	1 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants	6 Participants n=483 Participants	4 Participants n=36 Participants	4 Participants n=10 Participants	5 Participants n=115 Participants	25 Participants n=40 Participants	3 Participants n=8 Participants	17 Participants n=62 Participants	76 Participants n=95 Participants
Age, Customized >=65 years	2 Participants n=93 Participants	5 Participants n=4 Participants	5 Participants n=27 Participants	4 Participants n=483 Participants	1 Participants n=36 Participants	3 Participants n=10 Participants	1 Participants n=115 Participants	9 Participants n=40 Participants	1 Participants n=8 Participants	4 Participants n=62 Participants	35 Participants n=95 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	7 Participants n=4 Participants	5 Participants n=27 Participants	4 Participants n=483 Participants	2 Participants n=36 Participants	3 Participants n=10 Participants	5 Participants n=115 Participants	18 Participants n=40 Participants	0 Participants n=8 Participants	5 Participants n=62 Participants	51 Participants n=95 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants	6 Participants n=483 Participants	3 Participants n=36 Participants	4 Participants n=10 Participants	1 Participants n=115 Participants	16 Participants n=40 Participants	4 Participants n=8 Participants	16 Participants n=62 Participants	60 Participants n=95 Participants
Race/Ethnicity, Customized White	3 Participants n=93 Participants	8 Participants n=4 Participants	7 Participants n=27 Participants	7 Participants n=483 Participants	3 Participants n=36 Participants	4 Participants n=10 Participants	5 Participants n=115 Participants	28 Participants n=40 Participants	3 Participants n=8 Participants	15 Participants n=62 Participants	83 Participants n=95 Participants
Race/Ethnicity, Customized Black	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	4 Participants n=40 Participants	0 Participants n=8 Participants	3 Participants n=62 Participants	9 Participants n=95 Participants
Race/Ethnicity, Customized Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=40 Participants	0 Participants n=8 Participants	1 Participants n=62 Participants	4 Participants n=95 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	1 Participants n=8 Participants	1 Participants n=62 Participants	3 Participants n=95 Participants
Race/Ethnicity, Customized Other	0 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	3 Participants n=10 Participants	1 Participants n=115 Participants	1 Participants n=40 Participants	0 Participants n=8 Participants	1 Participants n=62 Participants	12 Participants n=95 Participants

PRIMARY outcome

Timeframe: Up to 28 days

Population: DLT evaluable population included only those participants who completed the DLT observation period throughout the course of 2 TSR-033 administrations (Day 1 and Day 15 in the first 28 days of study treatment) for Part 1A unless the participant discontinued TSR-033 (Part 1A) due to a DLT.

DLTs were assessed based on common terminology criteria for adverse events (CTCAE) v5.0 included drug-related AEs like grade\>=2 uveitis, eye pain, or blurred vision that does not resolve with topical therapy within 2 weeks, grade ≥2 immune-related endocrine toxicity that required hormone replacement, grade 2 or 3 colitis or diarrhea that persisted without resolution to grade\<=1 for \>=7days despite adequate immune suppressive therapy, grade 3 or 4 immune-related AEs (irAE) without resolution to grade\<=1 or baseline within 8 days despite adequate immune suppressive therapy, any grade clinically significant (CS) irAE requiring treatment discontinuation, other grade\>=3 non-hematologic toxicity, any CS grade\>=3 non-hematologic laboratory abnormality, any CS hematologic toxicity and any death that is not clearly attributed to the underlying disease or extraneous causes. CTCAE defines Grade 0 as normal, 1 as mild, 2 as moderate, 3 as severe and Grade 4 as life-threatening consequences.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=3 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=6 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) n=6 Participants In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) n=6 Participants In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 1A: Number of Participants Experiencing Dose Limiting Toxicity (DLT)	0 Participants	1 Participants	0 Participants	0 Participants	—	—	—

PRIMARY outcome

Timeframe: Up to 42 days

Population: DLT evaluable population included the assessment of DLTs in Part 1C included only those participants who completed the DLT observation period throughout the course of 2 TSR-033 + dostarlimab administrations (Day 1 and Day 21 in the first 42 days of study treatment), for Part 1C unless the participant discontinued TSR-033 + dostarlimab (Part 1C) due to a DLT.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=5 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=7 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) n=6 Participants In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 1C: Number of Participants Experiencing DLT	0 Participants	0 Participants	0 Participants	—	—	—	—

PRIMARY outcome

Timeframe: Up to 30 days

Population: DLT evaluable population included the assessment of DLTs in Part 2B included only those participants completing the DLT observation period throughout the course of 2 TSR-033 + dostarlimab administrations (Day 3 and Day 17 in the first 30 days of study treatment), for Part 2B unless the participant discontinued TSR-033 + dostarlimab (Part 2B) due to a DLT.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=4 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=21 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 2B: Number of Participants Experiencing DLT	0 Participants	0 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to approximately 51 months

Population: Safety population included all participants who receive any amount of study drug.

SAEs are any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is an important medical event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. TEAEs are defined as any new AE that begins, or any pre-existing condition that worsens in severity, after at least 1 dose of study treatment administration. Immune-related adverse events of interest (irAEs) are defined as any \>= Grade 2 AEs based on a pre-specified list. CTCAE defines Grade 0 as normal, 1 as mild, 2 as moderate, 3 as severe and Grade 4 as life-threatening consequences.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=3 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) n=11 Participants In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) n=5 Participants Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) n=7 Participants Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) n=6 Participants Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 1: Number of Participants With Serious Adverse Events (SAEs), Treatment-emergent AEs (TEAEs)and Immune-related AEs (irAEs) SAEs	1 Participants	5 Participants	2 Participants	1 Participants	1 Participants	3 Participants	4 Participants
Part 1: Number of Participants With Serious Adverse Events (SAEs), Treatment-emergent AEs (TEAEs)and Immune-related AEs (irAEs) TEAEs	3 Participants	10 Participants	10 Participants	10 Participants	5 Participants	7 Participants	6 Participants
Part 1: Number of Participants With Serious Adverse Events (SAEs), Treatment-emergent AEs (TEAEs)and Immune-related AEs (irAEs) irAEs	0 Participants	4 Participants	2 Participants	2 Participants	2 Participants	3 Participants	4 Participants

PRIMARY outcome

Timeframe: Up to approximately 29 months

Population: Safety population

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=4 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=21 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 2B: Number of Participants With SAEs, TEAEs and irAEs SAEs	4 Participants	7 Participants	—	—	—	—	—
Part 2B: Number of Participants With SAEs, TEAEs and irAEs TEAEs	4 Participants	21 Participants	—	—	—	—	—
Part 2B: Number of Participants With SAEs, TEAEs and irAEs irAEs	3 Participants	11 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to 51 months

Population: Safety population

Blood samples were collected for the analysis of hematology parameters and each parameter was graded according to national cancer institute (NCI)-common terminology criteria for adverse events (CTCAE) version 5.0. Grade 0: normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent non-missing measurement prior to the first administration of study drug. Data has been presented for the number of participants with hematology grade shifts from baseline grade to grade 3 and 4 for each parameter.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=3 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) n=11 Participants In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) n=5 Participants Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) n=7 Participants Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) n=6 Participants Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 1: Number of Participants With Grade Shift From Baseline in Hematology Parameters Lymphocytes, Grade 0 to Grade 3	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants
Part 1: Number of Participants With Grade Shift From Baseline in Hematology Parameters Lymphocytes, Grade 2 to Grade 3	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants
Part 1: Number of Participants With Grade Shift From Baseline in Hematology Parameters Lymphocytes, Grade 3 to Grade 3	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants	0 Participants	0 Participants
Part 1: Number of Participants With Grade Shift From Baseline in Hematology Parameters Neutrophils, Grade 0 to Grade 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Part 1: Number of Participants With Grade Shift From Baseline in Hematology Parameters Hemoglobin, Grade 1 to Grade 3	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Part 1: Number of Participants With Grade Shift From Baseline in Hematology Parameters Hemoglobin, Grade 2 to Grade 3	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 29 months

Population: Safety population

Blood samples were collected for the analysis of hematology parameters and each parameter was graded according to national cancer institute (NCI)-common terminology criteria for adverse events (CTCAE) version 5.0. Grade 0: normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent non-missing measurement prior to the first administration of study drug. Data have been presented for the number of participants with hematology grade shifts from baseline grade to grade 3 and 4 for each parameter. WBC is white blood cells.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=4 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=21 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 2B: Number of Participants With Grade Shift From Baseline in Hematology Parameters Hemoglobin, Grade 2 to Grade 3	0 Participants	2 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade Shift From Baseline in Hematology Parameters Lymphocytes, Grade 0 to Grade 3	1 Participants	2 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade Shift From Baseline in Hematology Parameters Lymphocytes, Grade 0 to Grade 4	1 Participants	0 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade Shift From Baseline in Hematology Parameters Lymphocytes, Grade 2 to Grade 3	0 Participants	4 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade Shift From Baseline in Hematology Parameters Neutrophils, Grade 0 to Grade 3	1 Participants	8 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade Shift From Baseline in Hematology Parameters Neutrophils, Grade 0 to Grade 4	1 Participants	1 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade Shift From Baseline in Hematology Parameters Platelets, Grade 0 to Grade 3	0 Participants	1 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade Shift From Baseline in Hematology Parameters WBC (Leukopenia), Grade 0 to Grade 3	1 Participants	4 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade Shift From Baseline in Hematology Parameters WBC (Leukopenia), Grade 0 to Grade 4	1 Participants	0 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to 51 months

Population: Safety population

Blood samples were collected for the analysis of clinical chemistry parameters and each parameter was graded according to national cancer institute (NCI)-common terminology criteria for adverse events (CTCAE) version 5.0. Grade 0: normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent non-missing measurement prior to the first administration of study drug. Data have been presented for the number of participants with clinical chemistry grade shifts from baseline grade to grade 3 and 4 for each parameter.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=3 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) n=11 Participants In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) n=5 Participants Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) n=7 Participants Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) n=6 Participants Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 1: Number of Participants With Grade Shift From Baseline in Clinical Chemistry Parameters Hyperkalemia, Grade 0 to Grade 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Part 1: Number of Participants With Grade Shift From Baseline in Clinical Chemistry Parameters Hypoalbuminemia, Grade 2 to Grade 3	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Part 1: Number of Participants With Grade Shift From Baseline in Clinical Chemistry Parameters Hypokalemia, Grade 0 to Grade 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Part 1: Number of Participants With Grade Shift From Baseline in Clinical Chemistry Parameters Hypomagnesemia, Grade 0 to Grade 3	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 29 months

Population: Safety population

Blood samples were collected for the analysis of clinical chemistry parameters and each parameter was graded according to national cancer institute (NCI)-common terminology criteria for adverse events (CTCAE) version 5.0. Grade 0: normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent non-missing measurement prior to the first administration of study drug. Data have been presented for the number of participants with clinical chemistry grade shifts from baseline grade to grade 3 and 4 for each parameter.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=4 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=21 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 2B: Number of Participants With Grade Shift From Baseline in Clinical Chemistry Parameters Hypercalcemia, Grade 0 to Grade 4	0 Participants	2 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade Shift From Baseline in Clinical Chemistry Parameters Hypocalcemia, Grade 0 to Grade 4	0 Participants	2 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to 51 months

Population: Safety population

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=3 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) n=11 Participants In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) n=5 Participants Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) n=7 Participants Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) n=6 Participants Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 1: Number of Participants With Grade 3 and 4 Toxicities in Clinical Chemistry Parameters - Creatinine, Bilirubin, Alkaline Phosphatase Alkaline phosphatase	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Part 1: Number of Participants With Grade 3 and 4 Toxicities in Clinical Chemistry Parameters - Creatinine, Bilirubin, Alkaline Phosphatase Bilirubin	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Part 1: Number of Participants With Grade 3 and 4 Toxicities in Clinical Chemistry Parameters - Creatinine, Bilirubin, Alkaline Phosphatase Creatinine	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 29 months

Population: Safety population

Blood samples were collected for the analysis of clinical chemistry parameters and each parameter was graded according to national cancer institute (NCI)-common terminology criteria for adverse events (CTCAE) version 5.0. Grade 0: normal, Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent non-missing measurement prior to the first administration of study drug. Data have been presented for the number of participants with clinical chemistry grade 3 and 4 toxicities each parameter.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=4 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=21 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 2B: Number of Participants With Grade 3 and 4 Toxicities in Clinical Chemistry Parameters - Alanine Aminotransferase, Aspartate Aminotransferase, Creatinine, Bilirubin Alanine aminotransferase	1 Participants	0 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade 3 and 4 Toxicities in Clinical Chemistry Parameters - Alanine Aminotransferase, Aspartate Aminotransferase, Creatinine, Bilirubin Aspartate aminotransferase	1 Participants	1 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade 3 and 4 Toxicities in Clinical Chemistry Parameters - Alanine Aminotransferase, Aspartate Aminotransferase, Creatinine, Bilirubin Bilirubin	1 Participants	2 Participants	—	—	—	—	—
Part 2B: Number of Participants With Grade 3 and 4 Toxicities in Clinical Chemistry Parameters - Alanine Aminotransferase, Aspartate Aminotransferase, Creatinine, Bilirubin Creatinine	0 Participants	1 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to 51 months

Population: Safety population

12-lead ECG were obtained using an ECG machine. Participants were in supine or a semi-recumbent position (about 30 degrees of elevation) and rested for approximately 2 minutes before ECGs are recorded. ECG results included QT interval corrected for heart rate according to Bazett's formula (QTcB), QT interval corrected for heart rate according to Fridericia's formula (QTcF), QRS interval, PR Interval and Heart rate.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=3 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) n=11 Participants In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) n=5 Participants Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) n=7 Participants Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) n=6 Participants Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 1: Number of Participants With Post Baseline Abnormal Electrocardiogram (ECG) Results QTcF	1 Participants	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Part 1: Number of Participants With Post Baseline Abnormal Electrocardiogram (ECG) Results QTcB	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Part 1: Number of Participants With Post Baseline Abnormal Electrocardiogram (ECG) Results QRS	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Part 1: Number of Participants With Post Baseline Abnormal Electrocardiogram (ECG) Results Heart Rate	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Part 1: Number of Participants With Post Baseline Abnormal Electrocardiogram (ECG) Results PR Interval	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 29 months

Population: Safety population

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=4 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=21 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 2B: Number of Participants With Post Baseline Abnormal ECG Results QTcF	1 Participants	2 Participants	—	—	—	—	—
Part 2B: Number of Participants With Post Baseline Abnormal ECG Results QTcB	1 Participants	5 Participants	—	—	—	—	—
Part 2B: Number of Participants With Post Baseline Abnormal ECG Results QRS	1 Participants	2 Participants	—	—	—	—	—
Part 2B: Number of Participants With Post Baseline Abnormal ECG Results Heart Rate	0 Participants	2 Participants	—	—	—	—	—
Part 2B: Number of Participants With Post Baseline Abnormal ECG Results PR Interval	0 Participants	1 Participants	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to 30 months

Population: Efficacy population included all participants who received any amount of TSR-033.

ORR is defined as percentage of participants achieving complete response (CR) or partial response (PR) as assessed by the investigator per response evaluation criteria in solid tumors (RECIST)v1.1. CR defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter. PR defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=34 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 2A: Objective Response Rate (ORR)	2.9 Percentage of participants Interval 0.1 to 15.3	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and post-dose 15 minute, 30 minute, 1.5, 3, 24, 48, 96 and 168 hour

Population: Pharmacokinetic (PK) population included all partiocipants who received any amount of TSR 033 and/or dostarlimab and have ≥1 measurable drug concentration. Only those participants with data available at specified time points have been analyzed.

Blood samples were collected for pharmacokinetic (PK) analysis of TSR-033 when administered intravenously as monotherapy. PK parameter was determined using standard non-compartmental methods.

Outcome measures

Outcome measures
Measure	Part 1AB - TSR-033 [20 Milligrams (mg)] n=3 Participants In part 1a, participants with advanced or metastatic solid tumors received 20 mg TSR-033 via 30-minute intravenous (IV) infusion once every 2 weeks (Q2W).	Part 1AB - TSR-033 (80 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1AB - TSR-033 (240 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W	Part 1AB: TSR-033:Part 1AB - TSR-033 (720 mg) n=10 Participants In part 1a, participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion once Q2W. In part 1b, additional participants enrolled in this dose level to characterize the PK profile of TSR-033 and assess PDy data followed by treatment with TSR-033 dosed on day 1, and then once Q2W.	Part 1C - TSR-033 (80 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 80 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once every 3 weeks (Q3W).	Part 1C - TSR-033 (240 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 240 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.	Part 1C - TSR-033 (720 mg) + Dostarlimab (500 mg) Participants with advanced or metastatic solid tumors received 720 mg TSR-033 via 30-minute IV infusion in combination with 500 mg dostarlimab on day 1, and then once Q3W.
Part 1ab: Area Under the Concentration-time Curve From Time Zero to Last Measurable Concentration (AUC [0-last]) of TSR-033	606.4256 Hourmicrogram/millilitre (hug/mL) Geometric Coefficient of Variation 32.65	2601.731 Hourmicrogram/millilitre (hug/mL) Geometric Coefficient of Variation 70.3423	8176.4963 Hourmicrogram/millilitre (hug/mL) Geometric Coefficient of Variation 29.4644	23763.7645 Hourmicrogram/millilitre (hug/mL) Geometric Coefficient of Variation 48.7606	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and post-dose 15 minute, 30 minute, 1, 1.5, 3, 24, 48, 96, 168, 336 and 504 hour