A clinical trial of a new drug known as Ti-061, that will take place in patients with tumors. Ti-061 will be assessed as a standalone drug as well as being assessed when taken with another drug, called Pembrolizumab.

Phase 1

• Conditions: Advanced malignancies; MedDRA version: 19.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 19.1Level: PTClassification code 10066476Term: Haematological malignancySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004372-22-GB
• Lead Sponsor: Tioma Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-02-14
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 320

Inclusion Criteria

Patients meeting all of the following inclusion criteria at screening/day-1 of first dosing will be eligible for participation in the study.
1. Informed consent signed by the patient.
2. Male or female patients =18 years of age.
3. Histological or cytological diagnosis as follows:
a. In the escalation phase of the study, patients must have a histological or cytological diagnosis of melanoma or any type of carcinoma or sarcoma, progressive metastatic disease, or progressive locally advanced disease not amenable to local therapy. Part A only: Patients with metastatic breast cancer may have bone-only disease.
b. In the tumor-type-specific expansion cohorts, patients must have a histological diagnosis of the relevant tumor type. Refer to protocol for specific tumor types for Part A and Part B.
4. Prior therapies:
Refer to the protocol for further details on inclusion criteria on prior therapies for Part A and Part B of the study.
5. Patient must have demonstrated PD after the most recent treatment regimen (or within 3 months prior to enrollment in the case of treatment-naïve patients).
6. At least one non-target lesion for escalation cohorts and at least one target lesion not impacted by study biopsy, or two lesions if one is impacted by biopsy, for the expansion cohorts per RECIST 1.1 (Part A only: except for patients with HRpos MBC, who may have bone-only disease).
7. If not menopausal or surgically sterile, patients must be willing to practice at least one of the following methods of birth control for at least a (partner’s) menstrual cycle before and for 3 months after study drug administration: (1) Total abstinence from sexual intercourse with a member of the opposite sex; (2) Sexual intercourse with vasectomized male/sterilized female partner; (3) Hormonal female contraceptive (oral, parenteral, or transdermal) for at least 3 consecutive months prior to investigational product administration (Part A only: when not clinically contraindicated as in breast, ovarian and endometrial cancers); (4) Other acceptable forms of birth control (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicide or cream); (5) Use of an intrauterine contraceptive device.
8. Resolution of prior-therapy-related adverse effects (Part A: including immune-related adverse effects, but excluding alopecia; Part B: excluding alopecia and immune-related adverse effects of CPIs – see Exclusion #10) to = Grade 1 per CTCAE, and no treatment for these AEs for at least 4 weeks prior to the time of enrollment.
9. Part A: Minimum of 2 weeks since last dose of other hormone therapy or 3 weeks since last dose of other systemic cancer therapy or radiotherapy (>6 weeks in case of nitrosureas, antibody-drug conjugate or radio-immuno conjugate therapy). Part B: Minimum of 12 weeks from the first dose of CPI and >4 weeks from the last dose of CPI and >3 weeks from last dose of other systemic cancer therapy or radiotherapy (>6 weeks in case of nitrosureas, antibody-drug conjugate or radio-immuno conjugate therapy).
10. Part B: For expansion cohorts allowing prior CPIs: resolution of CPI-related AEs (including irAEs) back to Grade 0-1 and =10 mg/day prednisone or equivalent for irAEs for at least two weeks prior to first dose of study drug. No history of severe irAEs from CPI CTCAE Grade 4 requiring steroid treatment. No history of CTCAE Grade 3 irAEs from CPI requiring steroid treatment (>10 mg/day prednisone or equivalent dose) for >12 weeks.
11. Has negative v

Exclusion Criteria

Patients meeting any of the following exclusion criteria at Screening/day -1 of first dosing will not be enrolled in the study:
1. Patient previously had a severe hypersensitivity reaction to treatment with another mAb.
2. Part B only: For patients in the expansion cohorts, history of intolerance to any anti-PD-(L)1.
3. Patient has ECOG PS >1.
4. Part A only: Prior treatment with a CPI (anti-PD-1, PD-L1 or CTLA-4).
5. Prior RBC transfusion within 3 months of screening.
6. Prior organ or stem cell transplant.
7. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
8. Patients with a history of any condition known to be associated with reduced RBC lifespan e.g. Thalassemia trait, G6PD deficiency.
9. Patients with extensive (25%) disease involvement of bone marrow.
10. Patients with extensive (25%) irradiation of the bone marrow.
11. Part B only: History of pneumonitis or interstitial lung disease.
12. Patients with symptomatic ascites or pleural effusion. A patient who is clinically stable for at least two weeks following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
13. Patient has known active CNS primary tumor or metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no evidence of new or enlarging brain metastases and are off steroids for at least 15 days prior to first dose of study drug.
14. Patient has a known history of a hematologic malignancy, malignant primary brain tumor, or of another malignant primary solid tumor (other than that under study), unless the patient has undergone potentially curative therapy with no evidence of that disease for 3 years.
Note: The time requirement for no evidence of disease for 3 years does not apply to the tumor for which a patient is enrolled in the study. The time requirement also does not apply to patients who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
15. Patient has active infection requiring therapy.
16.
Part A: Use of systemic corticosteroids within 15 days or other immunosuppressive drugs within 30 days prior to start of the study.
Part B: Use of systemic corticosteroids >10 mg/day prednisone or equivalent within 15 days or other immunosuppressive drugs within 30 days prior to start of the study.
17. Part B: For patients who will receive pembrolizumab:
a. Prior thoracic radiation with a dose > 30 Gy within 26 weeks.
b. Patients with a tumor at a critical anatomic location, like abutting the thecal sac or compressing a main-stem bronchus, such that an impending catastrophic event is possible, should have that tumor lesion radiated prior to treatment.
c. Patient has risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess, abdominal carcinomatosis).
18. Patient has received an investigational product or been treated with an investigational device within 30 days prior to first drug administration.
19. History or clinical evidence of any surgical or medical condition which the investigator judges as likely to interfere with the results of the study or pose an additional risk in participating e.g., rapidly progressive or uncontrolled disease invol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified