TRQ15-01 in Patients With Relapsed/Refractory Solid Tumors and Lymphomas

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 lymphomas. NCT# 03815682

Inclusion Criteria:

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
   • Melanoma
   • Clear cell cancer of the kidney
   • Head and neck squamous cell cancer
   • Urothelial cancer
   • Lymphoma
   • Sarcomas
   • 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.

Exclusion Criteria:

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 mL/min
   • 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 be eligible
   • 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 eligible
   • 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 separation methods

5. Impaired cardiac function or clinically significant cardiac disease, including any of the following:

   • 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 entry
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 to enroll.
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 treatment.
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 treatment.
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 sponsor.
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 manufacturing time.

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 patient
    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 study treatment.

    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 period.

Conditions:
• Solid Tumor
• Lymphoma