The purpose of this study is to assess the safety and tolerability of escalating doses of
TRQ15-01 in patients with relapsed/refractory/metastatic or locally-advanced solid tumors and
This is a first-in-human, Phase 1, open-label, multicenter, dose escalation study designed to
determine the safety and tolerability of TRQ15-01 in patients with relapsed/refractory or
locally advanced solid tumors or lymphomas. The study will include 2 dosing periods: a Dose
Escalation Phase followed by an Expansion Phase.
1. Written informed consent must be obtained prior to any study procedures.
2. Age ≥ 18 years (or ≥ 16 years at Children's National Medical Center).
3. Histologically- or cytologically-confirmed relapsed/refractory metastatic or
locally-advanced solid tumor or lymphoma whose disease has progressed despite all
appropriate curative or life-prolonging treatments, are intolerant to these therapies
or have refused standard treatment.
Note: Cohort enrollment may be limited to potentially immune-responsive tumor types
meeting the above criterion during the first approximately 2 weeks of the enrollment
period of each cohort due to their potential to respond to and activate TRQ15-01:
- Non-small cell lung cancer
- Clear cell cancer of the kidney
- Head and neck squamous cell cancer
- Urothelial cancer
- Ovarian Cancer
- Other tumors determined likely to be immunogenic based upon emerging data as
discussed during escalation teleconferences
4. Patients with measurable disease (at least one measurable lesion, at least 1.0 cm in
diameter), documented within 10 weeks of their projected C1D1 visit, as determined by
RECIST v1.1 for patients with solid tumors or Lugano classification or if nodal, at
least 1.5cm or greater in the short axis dimension for patients with lymphoma.
5. ECOG Performance Status ≤ 1.
6. Patient must have a site of disease amenable to biopsy and be a candidate for tumor
biopsy according to the treating institution's guidelines. Patient must be willing to
undergo tumor biopsies, one new tumor biopsy during screening period 2 or provide a
suitable archival sample for assessment of the tumor microenvironment, and during
therapy on this study.
1. Previously identified hypersensitivity to components of TRQ15-01 or excipients.
2. Patients with T-cell lymphomas or small lymphocytic lymphoma.
3. Presence of active central nervous system (CNS) disease unless the CNS metastases have
been previously treated, the patient is clinically stable, asymptomatic and the
patient has discontinued corticosteroids for at least 4 weeks prior to enrollment.
4. Patient having out of range laboratory values defined as:
- Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 40
- Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are
excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
- Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) > 3 x ULN,
except for patients that have tumor involvement of the liver, who are excluded if
ALT > 5 x ULN
- Absolute neutrophil count ≤ 1.0 x 109/L
- 0.5 x 109/L and increasing following prior myelosuppressive treatment will
- Absolute lymphocyte count ≤ 1.0 x 109/L
- Platelet count ≤ 75 x 109/L absent platelet transfusion for 2 weeks
- Hemoglobin (Hgb) ≤ 9 g/dL absent RBC transfusion for 2 weeks
- 8 g/dL and increasing following prior myelosuppressive treatment will be
- Potassium, magnesium, calcium or phosphate abnormality > CTCAE grade 1 despite
appropriate oral replacement therapy
- Serum triglycerides > 500 mg/dL due to potential interference with cell
5. Impaired cardiac function or clinically significant cardiac disease, including any of
- Clinically significant and/or uncontrolled heart disease such as congestive heart
failure requiring treatment (NYHA grade ≥ 2), uncontrolled hypertension or
clinically significant arrhythmia
- Acute myocardial infarction or unstable angina pectoris < 6 months prior to study
6. Patients with active, known or suspected autoimmune disease. Patients with vitiligo,
type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition only
requiring hormone replacement, psoriasis not requiring systemic treatment, or
conditions not expected to recur in the absence of an external trigger are permitted
7. Known (testing not required) Human Immunodeficiency Virus (HIV), active Hepatitis B
(HBV) or active Hepatitis C (HCV) virus.
8. Malignant disease, other than that being treated in this study expected to interfere
with the assessment of efficacy in the opinion of the investigator.
9. Active infection requiring systemic antibiotic therapy.
10. Patients requiring chronic treatment with systemic steroid therapy, other than
replacement dose steroids in the setting of adrenal insufficiency. Topical, inhaled,
nasal, or ophthalmic steroids are allowed.
11. Patients receiving systemic treatment with any immunosuppressive medication.
12. Use of any live vaccines against infectious diseases (e.g. influenza, varicella,
pneumococcus) within 4 weeks of initiation of study treatment.
13. Major surgery within 4 weeks of the first dose of study treatment (mediastinoscopy,
insertion of a central venous access device, and insertion of a feeding tube are not
considered major surgery).
14. Participation in an interventional, investigational study within 2 weeks of the first
dose of study treatment.
15. Presence of ≥ CTCAE grade 2 toxicity from prior therapy (except alopecia, peripheral
neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior cancer
16. Initiation of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GMCSF,
M-CSF) ≤2 weeks prior to start of study drug. An erythroid stimulating agent is
allowed as long as it was initiated at least 2 weeks prior to the first dose of study
17. An unresolved adverse event (must be ≤ Grade 1 or the patient's baseline).
18. Prior treatment with CAR T-cell therapy.
19. Prior allogeneic stem cell transplant.
20. Patients who were required to discontinue PD-1/PDL-1, CTLA-4 or other immunomodulatory
antibodies due to ≥ grade 3 irAE may be included following discussion with the
21. Patients with a history of > 3 lines of chemotherapy in the metastatic setting may be
eligible for enrollment following discussion with the sponsor.
22. Clinical or radiological disease progression (excluding pseudoprogression) on
PD-1/PDL-1, CTLA-4 inhibitors within 8 weeks of the initial dose of the prior
treatment may only be enrolled following discussion with the sponsor to account for
23. Prior therapy with PD-1/PDL-1, CTLA-4 or other immunomodulatory antibodies inhibitors:
1. ≤2 weeks prior to the apheresis procedure
2. ≤4 weeks prior to the first dose of study treatment
24. Systemic anti-cancer therapy within 5 half-lives or 2 weeks; whichever occurs first,
of the first dose of study treatment.
a. Systemic cytotoxic agents that have major delayed toxicity, e.g. mitomycin C and
nitrosoureas, ≤ 6 weeks prior to the first dose of study treatment
25. Any medical condition that would, in the investigator's judgment, prevent the
patient's participation in the clinical study due to safety concerns, compliance with
clinical study procedures or interpretation of study results.
26. Lactating or pregnant women confirmed by a positive hCG laboratory test.
27. Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during study treatment and for 30 days after the last dose of study treatment. Highly
effective contraception methods include:
1. Female sterilization, total hysterectomy or tubal ligation at least 6 weeks
before taking study treatment
2. Male sterilization (at least 6 months prior to screening). For female patients on
the study the vasectomized male partner should be the sole partner for that
3. Use of oral (estrogen and progesterone), injected or implanted combined hormonal
methods of contraception or placement of an intrauterine device (IUD) or
intrauterine system (IUS) or other forms of hormonal contraception that have
comparable efficacy (failure rate <1%), for example hormone vaginal ring or
transdermal hormone contraception In case of use of oral contraception women
should have been stable on the same pill for a minimum of 3 months before taking
Women are considered post-menopausal and not of child bearing potential if they have
had 12 months of natural amenorrhea with an appropriate clinical profile or have had
surgical bilateral oophorectomy or tubal ligation at least 6 weeks prior to the first
dose of study treatment.
28. Sexually active males unless they use a condom during intercourse while taking drug
and for 30 days after stopping study treatment and should not father a child in this