CLINICAL TRIAL / NCT02817633
A Study of TSR-022 in Participants With Advanced Solid Tumors (AMBER)
- Interventional
- Active
- NCT02817633
Contact Information
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)
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 in combination with TSR-042 or docetaxel and as monotherapy
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
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.
Inclusion Criteria for Participants in Part 2 Cohort E
- Participant is greater than or equal to (>=)18 years old, is able to understand the
study procedures, and agrees to participate in the study by providing written informed
consent which includes compliance with the requirements and restrictions listed in the
Informed consent form (ICF) and protocol.
- Participant has histologically or cytologically proven advanced or metastatic NSCLC,
and only squamous or nonsquamous cell carcinoma.
- Participant has received no more than 2 prior lines of therapy for advanced or
metastatic disease, which must only include a platinum-based (eg, cisplatin,
carboplatin) doublet chemotherapy regimen and an anti-PD-1 or anti-PD-L1 antibody (no
other biologic agents alone or in combination; novel combinations are not allowed).
Participants previously treated with targeted therapies, including angiogenesis
inhibitors (eg, bevacizumab, ramucirumab, lenvatinib), are not eligible.
- Participant has measurable disease, that is, presenting with at least 1 measurable
lesion per RECIST v1.1 as determined by the local site Investigator/radiology
assessment. Target lesions situated in a previously irradiated area are considered
measurable if disease progression has been demonstrated in such lesions and if there
are other target lesions. If there is only 1 target lesion that was previously
irradiated, the participant is not eligible.
- Participant has documented radiological disease progression on prior platinum-based
chemotherapy and on prior anti-PD-1 or anti-PD-L1 therapy according to RECIST v1.1.
- Participant agrees to submit an archival formalin fixed paraffin embedded (FFPE) tumor
tissue specimen that was collected on or after diagnosis of metastatic disease from
location(s) not irradiated prior to biopsy. Both tissue block and freshly cut slides
are acceptable. If archival tissue is not available, the participant must undergo
biopsy prior to study entry.
- Participant has an ECOG performance status score of 0 or 1.
- Participant has a life expectancy of at least 3 months and is anticipated to be able
to complete 4 cycles of docetaxel treatment.
- Participant has adequate organ function as defined in the protocol
- Contraceptive use by male and female participants should be consistent with local
regulations regarding the methods of contraception for those participating in clinical
studies.
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 receptor tyrosine kinase (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.
Exclusion Criteria for Participants in Part 2 Cohort E
- Participant has been previously treated with an anti PD 1, anti PD L1, or anti PD L2
agent that resulted in permanent discontinuation due to an AE
- Participant has been previously treated with an anti TIM 3 or anti cytotoxic T
lymphocyte-associated protein 4 (CTLA 4) agent or docetaxel.
- Participant has a documented sensitizing EGFR, ALK, or ROS-1 mutation. Participants
whose tumors have not been tested for these driver mutations and therefore who have
unknown driver mutation status are not eligible. Participants with squamous histology
do not need to be tested for these driver mutations.
- Participant had radiological or clinical disease progression (that is [ie,] worsening
performance status, clinical symptoms, and laboratory data) <=8 weeks after initiation
of prior anti PD 1 or anti-PD-L1 antibody. The clinical disease progression should
have been confirmed by a subsequent radiological scan.
- Participant has received radiation to the lung that is >30 gray (Gy) within 6 months
prior to the first dose of study treatment.
- Participant has completed palliative radiotherapy within 7 days prior to the first
dose of study treatment.
- Participant has an additional malignancy or a history of prior malignancy, with the
exception of adequately treated basal or squamous skin cancer, cervical carcinoma in
situ, or bladder carcinoma in situ without evidence of disease, or had a malignancy
treated with curative intent and with no evidence of disease recurrence for 5 years
since the initiation of that therapy.
- Participant has known new or progressive brain metastases and/or leptomeningeal
metastases. Participants who have received prior therapy for their brain metastases
and have radiologically stable central nervous system disease may participate,
provided they are neurologically stable for at least 4 weeks before study entry and
are off corticosteroids within 3 days prior to the first dose of study treatment.
- Participant has tested positive for the following at Screening or within 3 months
before the first dose of study treatment:
- Presence of hepatitis B surface antigen.
- Presence of hepatitis C antibody in the absence of an Ribonucleic acid (RNA) test for
hepatitis C virus.
- Participant has known human immunodeficiency virus (HIV) (positive for HIV 1 or HIV 2
antibodies).
- Participant has active autoimmune disease that required systemic treatment in the past
2 years, is immunocompromised in the opinion of the Investigator, or is receiving
systemic immunosuppressive treatment. Replacement therapy (eg, thyroxine, insulin, or
physiologic corticosteroid replacement therapy of prednisone, or equivalent, for
adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
- Participant has received systemic steroid therapy within 3 days prior to the first
dose of the study treatment or is receiving any other form of immunosuppressive
medication. Replacement therapy is not considered a form of systemic therapy. Use of
inhaled corticosteroids, local steroid injection, or steroid eye drops is allowed.
- Participant has current interstitial lung disease, current pneumonitis, or a history
of pneumonitis that required the use of glucocorticoids to assist with management.
Lymphangitic spread of the NSCLC is not exclusionary.
- Participant does not meet requirements per local prescribing guidelines for receiving
treatment with docetaxel, including severe hypersensitivity reactions to drugs
formulated with polysorbate 80.
- Participant has received prior anticancer therapy (chemotherapy, targeted therapies,
radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half life of
the most recent therapy prior to study Day 1, whichever is shorter.