A Study of TSR-022 in Participants With Advanced Solid Tumors (AMBER)

Sponsor

Tesaro, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT02817633

Collaborator

(none)

369

Enrollment

Locations

Arms

98.9

Anticipated Duration (Months)

5.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a first-in-human study evaluating the anti-T cell immunoglobulin and mucin containing protein-3 (TIM-3) antibody TSR-022. The study will be conducted in 2 parts with Part 1 consisting of dose escalation and Part 2 dose expansion. Part 1 will determine the recommended Phase 2 dose (RP2D) of TSR-022 and Part 2 will evaluate the antitumor activity of TSR-022.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: TSR-022 Drug: Nivolumab Drug: TSR-042 Drug: TSR-033 Drug: Docetaxel Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

369 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

This is a multi-center, open-label, first-in-human Phase 1 study.This is a multi-center, open-label, first-in-human Phase 1 study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors (AMBER)

Actual Study Start Date :

Jul 8, 2016

Anticipated Primary Completion Date :

Oct 5, 2023

Anticipated Study Completion Date :

Oct 3, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1a: TSR-022 monotherapy	Drug: TSR-022 TSR-022 will be administered.
Experimental: Part 1b: TSR-022 in combination with nivolumab	Drug: TSR-022 TSR-022 will be administered. Drug: Nivolumab Nivolumab will be administered.
Experimental: Part 1c: TSR-022 in combination with TSR-042	Drug: TSR-022 TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered.
Experimental: Part 1d: TSR-022 in combination with TSR-042 and TSR-033	Drug: TSR-022 TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. Drug: TSR-033 TSR-033 will be administered.
Experimental: Part 1e: TSR-022 with TSR-042 (not previously treated with anti-programmed death ligand [PD-{L}]1)	Drug: TSR-022 TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered.
Experimental: Part 1f: TSR-022 in combination with TSR-042 and Docetaxel	Drug: TSR-022 TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. Drug: Docetaxel Docetaxel will be administered.
Experimental: Part 1g: TSR-022 in combination with TSR-042, pemetrexed, and cisplatin	Drug: TSR-022 TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. Drug: Pemetrexed Drug: Cisplatin
Experimental: Part 1h: TSR-022 in combination with TSR-042, pemetrexed, and carboplatin	Drug: TSR-022 TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered. Drug: Pemetrexed Drug: Carboplatin
Experimental: Part 2: Cohort A Melanoma-TSR-022 as monotherapy	Drug: TSR-022 TSR-022 will be administered.
Experimental: Part 2: Cohort A Melanoma-TSR-022 with TSR-042	Drug: TSR-022 TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered.
Experimental: Part 2:Cohort B Non-small cell lung cancer-TSR-022-monotherapy	Drug: TSR-022 TSR-022 will be administered.
Experimental: Part 2:Cohort B Non-small cell lung cancer-TSR-022 with TSR-042	Drug: TSR-022 TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered.
Experimental: Part 2:Cohort C Colorectal cancer-TSR-022 as monotherapy	Drug: TSR-022 TSR-022 will be administered.
Experimental: Part 2:Cohort C Colorectal cancer-TSR-022 with TSR-042	Drug: TSR-022 TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered.
Experimental: Part 2: Cohort D-TIM-3 selected non-small cell lung cancer (NSCLC)	Drug: TSR-022 TSR-022 will be administered. Drug: TSR-042 TSR-042 will be administered.

Outcome Measures

Primary Outcome Measures

Part 1 (a): Number of participants achieving dose limiting toxicity (DLTs) [Up to 28 days]
Part 1 (b,c,d): Number of participants achieving dose limiting toxicity (DLTs) [Up to 42 days]
Part 1 (f,g,h): Number of participants achieving dose limiting toxicity (DLTs) [Up to 21 days]
Part 1: Number of participants with adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, treatment emergent adverse events (TEAEs), TEAEs leading to death and immune-related adverse events (irAEs) [Up to 2 years]
Part 1: Number of participants with clinically significant changes in laboratory parameters, vital signs, electrocardiogram (ECG) findings, Eastern Cooperative Oncology Group (ECOG) status, physical examination and use of concomitant medications [Up to 2 years]
Part 1 (E) and Part 2: Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 [Up to 2 years]

Secondary Outcome Measures

Part 1 (c, d, e, f, g, h): Number of participants with anti-TSR-022, anti-TSR-042 [Up to 2 years]
Part 1 (d): Number of participants with anti-TSR-033 antibodies [Up to 2 years]
Part 1 (a, b, c, d, f, g, h): ORR by RECIST v 1.1 [Up to 2 years]
Part 2: ORR by Immune related RECIST (irRECIST) [Up to 2 years]
Part 2: Duration of response (DOR) by RECIST v 1.1 and irRECIST [Up to 2 years]
Parts 1 and 2: Disease control rate (DCR) by RECIST v 1.1 [Up to 2 years]
Part 2: DCR by irRECIST [Up to 2 years]
Part 2: Progression-free survival (PFS) by RECIST v 1.1 and irRECIST [Up to 2 years]
Parts 1 and 2: Serum concentration of TSR-022 [Up to 2 years]
Part 1d: Serum concentration of TSR-033 [Up to 2 years]
Part 1 (c, d, e, f, g ,h): Serum concentration of TSR-042 [Up to 2 years]
Part 2: Serum concentration of TSR-042 [Up to 2 years]
Part 2: Overall survival (OS) [Up to 2 years]
Part 1a: Minimum plasma concentration (Cmin) of TSR-022 as monotherapy [Up to 2 years]
Part 1b: Cmin of TSR-022 in combination with nivolumab [Up to 2 years]
Part 1c: Cmin of TSR-022 in combination with TSR-042 [Up to 2 years]
Part 1d: Cmin of TSR-022 in combination with TSR-042 and TSR-033 [Up to 2 years]
Part 1a: Area under the concentration × time curve from time 0 to infinity AUC (0-inf) of TSR-022 as monotherapy [Up to 2 years]
Part 1b: AUC (0-inf) of TSR-022 in combination with nivolumab [Up to 2 years]
Part 1c: AUC (0-inf) of TSR-022 in combination with TSR-042 [Up to 2 years]
Part 1d: AUC (0-inf) of TSR-022 in combination with TSR-042 and TSR-033 [Up to 2 years]
Part 1a: Area under the concentration time curve from time 0 to last assessment (AUC 0-last) of TSR-022 as monotherapy [Up to 2 years]
Part 1b: AUC (0-last) of TSR-022 in combination with nivolumab [Up to 2 years]
Part 1c: AUC (0-last) of TSR-022 in combination with TSR-042 [Up to 2 years]
Part 1d: AUC (0-last) of TSR-022 in combination with TSR-042 and TSR-033 [Up to 2 years]
Part 1a: Terminal half life (1/2) of TSR-022 as monotherapy [Up to 2 years]
Part 1b: t1/2 of TSR-022 and in combination with nivolumab [Up to 2 years]
Part 1c: t1/2 of TSR-022 in combination with TSR-042 [Up to 2 years]
Part 1d: t1/2 TSR-022 in combination with TSR-042 and TSR-033 [Up to 2 years]
Part 1a: Area under the concentration × time curve during the dosing interval (AUCtau) of TSR-022 as monotherapy [Up to 2 years]
Part 1b: AUCtau of TSR-022 and in combination with nivolumab [Up to 2 years]
Part 1c: AUCtau of TSR-022 in combination with TSR-042 [Up to 2 years]
Part 1d: AUCtau of TSR-022 in combination with TSR-042 and TSR-033 [Up to 2 years]
Part 1: Number of participants with anti-drug antibodies (ADAs) to TSR-022 [Up to 2 years]
Part 2: Number of participants with ADA to anti-TSR-022 [Up to 2 years]
Part 1 (c, d, e, f, g ,h): Number of participants with ADA to TSR-042 [Up to 2 years]
Part 2: Number of Participants with ADA to TSR-042 [Up to 2 years]
Part 1d: Number of participants with ADA to TSR-033 [Up to 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Participant is at least 18 years of age.
Female participants of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the date of the first dose of study medication or be of non-childbearing potential.
Participant has an ECOG performance status of less than or equal to (<=)1.
Participant has adequate organ function.

Inclusion Criteria for Participants in Part 1 and Part 2 Cohorts A, B, and C:

Participant with advanced or metastatic solid tumor who meets the requirements for the part of the study/cohort he/she will participate in, as follows:
Part 2: Histologically proven advanced (unresectable) or metastatic solid tumor that is measurable by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST version 1.1 criteria
Inclusion Criteria for Participants in Part 2 Cohort D
Participants with advanced or metastatic NSCLC that is measurable by CT or MRI per

RECIST version 1.1 criteria and meet the following criteria:

NSCLC histology includes squamous or non-squamous cell carcinoma.
Participants have received no more than 2 prior lines of therapy, which must include a platinum-based chemotherapy (for example [e.g.], cisplatin, carboplatin) and an anti-PD-(L)1 antibody.
Participants must have documented radiographic progression by RECIST version 1.1 criteria on prior anti-programmed cell death protein (PD)-1 or anti-PD-(L)1 therapy.
Biopsies -All participants enrolled must undergo a biopsy prior to study entry, and the biopsy tissue must be submitted to the central laboratory for all participants in order to determine TIM 3 expression level prior to first dose. If a participant has had a biopsy prior to entering the 35-day screening period and within approximately 12 weeks of study treatment, that biopsy may be accepted as the Baseline fresh biopsy.

Exclusion Criteria

History of Grade greater than or equal to (>=)3 immune-related AE with prior immunotherapy, with the exception of non-clinically significant lab abnormalities.
Participant has known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis.
Participant has a known additional malignancy that progressed or required active treatment within the last 2 years. Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen may be included only after discussion with the Medical Monitor.
Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection requiring systemic therapy.
Participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 150 days after the last dose of study treatment.
Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.

Exclusion Criteria for Participants in Part 2 Cohort D

A participant with negative (as determined by Central Testing Lab) or unevaluable TIM-3 expression from tissue obtained prior to study entry will not be eligible for the study.
Participant has received prior therapy as defined below:
Prior treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agent that resulted in permanent discontinuation due to an AE.
Prior treatment with an anti-lymphocyte activation gene (LAG)-3 or anti-TIM-3.
Radiologic or clinical progression <= 8 weeks after initiation of prior anti-PD-1 or anti-PD-L1 antibody.
Participants with known epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) translocation, or ROS1 mutation.
Participant has received a vaccine other than a vaccine against severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) infection ("Coronavirus Disease 2019" [COVID-19]) within 7 days of planned start of study therapy. The use of all COVID-19 vaccines is allowed, with the exception of COVID-19 vaccines using the recombinant adenoviral vector platform within 30 days of planned start of study therapy. If a COVID-19 vaccine using this platform is to be administered within 30 days of planned start of study therapy, this must first be discussed with and approved by the Sponsor's Medical Monitor.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Goodyear	Arizona	United States	85338
2	GSK Investigational Site	Scottsdale	Arizona	United States	85258
3	GSK Investigational Site	Tucson	Arizona	United States	85704
4	GSK Investigational Site	Tucson	Arizona	United States	85711
5	GSK Investigational Site	Encinitas	California	United States	92024
6	GSK Investigational Site	Fountain Valley	California	United States	92708
7	GSK Investigational Site	Los Angeles	California	United States	90024
8	GSK Investigational Site	Los Angeles	California	United States	90025
9	GSK Investigational Site	San Marcos	California	United States	92069
10	GSK Investigational Site	Whittier	California	United States	90606
11	GSK Investigational Site	Aurora	Colorado	United States	80012
12	GSK Investigational Site	Aurora	Colorado	United States	80045
13	GSK Investigational Site	Denver	Colorado	United States	80218
14	GSK Investigational Site	Denver	Colorado	United States	80218
15	GSK Investigational Site	New Haven	Connecticut	United States	06511
16	GSK Investigational Site	Washington	District of Columbia	United States	20007
17	GSK Investigational Site	Jacksonville	Florida	United States	32224
18	GSK Investigational Site	Miami Beach	Florida	United States	33140
19	GSK Investigational Site	Sarasota	Florida	United States	34232
20	GSK Investigational Site	Tampa	Florida	United States	33612
21	GSK Investigational Site	Atlanta	Georgia	United States	30322
22	GSK Investigational Site	Augusta	Georgia	United States	30912
23	GSK Investigational Site	Arlington Heights	Illinois	United States	60005
24	GSK Investigational Site	Chicago	Illinois	United States	60637
25	GSK Investigational Site	Niles	Illinois	United States	60714
26	GSK Investigational Site	Iowa City	Iowa	United States	52242-1009
27	GSK Investigational Site	Wichita	Kansas	United States	67214
28	GSK Investigational Site	Louisville	Kentucky	United States	40202
29	GSK Investigational Site	Pikeville	Kentucky	United States	41501
30	GSK Investigational Site	Rockville	Maryland	United States	20850
31	GSK Investigational Site	Boston	Massachusetts	United States	02114
32	GSK Investigational Site	Detroit	Michigan	United States	48202
33	GSK Investigational Site	Rochester	Minnesota	United States	55905
34	GSK Investigational Site	Hackensack	New Jersey	United States	07601
35	GSK Investigational Site	Bronx	New York	United States	10461
36	GSK Investigational Site	New York	New York	United States	10016
37	GSK Investigational Site	Cincinnati	Ohio	United States	45242
38	GSK Investigational Site	Cleveland	Ohio	United States	44106
39	GSK Investigational Site	Toledo	Ohio	United States	43623
40	GSK Investigational Site	Eugene	Oregon	United States	97401
41	GSK Investigational Site	Portland	Oregon	United States	97213-2982
42	GSK Investigational Site	Bethlehem	Pennsylvania	United States	18015
43	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15213-2584
44	GSK Investigational Site	Charleston	South Carolina	United States	29425
45	GSK Investigational Site	Greenville	South Carolina	United States	29605
46	GSK Investigational Site	Nashville	Tennessee	United States	37203
47	GSK Investigational Site	Austin	Texas	United States	78705
48	GSK Investigational Site	Dallas	Texas	United States	75246
49	GSK Investigational Site	Fort Worth	Texas	United States	76104
50	GSK Investigational Site	Houston	Texas	United States	77030
51	GSK Investigational Site	Houston	Texas	United States	77030
52	GSK Investigational Site	Longview	Texas	United States	75601
53	GSK Investigational Site	McAllen	Texas	United States	78503-1298
54	GSK Investigational Site	San Antonio	Texas	United States	78229
55	GSK Investigational Site	Temple	Texas	United States	76508
56	GSK Investigational Site	Tyler	Texas	United States	75702
57	GSK Investigational Site	Weslaco	Texas	United States	78596
58	GSK Investigational Site	Fairfax	Virginia	United States	8613
59	GSK Investigational Site	Kennewick	Washington	United States	99336
60	GSK Investigational Site	Puyallup	Washington	United States	98373
61	GSK Investigational Site	Tacoma	Washington	United States	98405
62	GSK Investigational Site	Madison	Wisconsin	United States	53792
63	GSK Investigational Site	Madrid	Navarra	Spain	28027
64	GSK Investigational Site	Barcelona		Spain	08035
65	GSK Investigational Site	Girona		Spain	17007
66	GSK Investigational Site	L'Hospitalet De Llobregat		Spain	08908
67	GSK Investigational Site	Las Palmas De Gran Canaria		Spain	35016
68	GSK Investigational Site	Madrid		Spain	28040
69	GSK Investigational Site	Madrid		Spain	28041
70	GSK Investigational Site	Málaga		Spain	29010
71	GSK Investigational Site	Pamplona		Spain	31008
72	GSK Investigational Site	Valencia		Spain	46010