Ph. 1, Evaluation of Safety, Tolerability, PK, Anti-tumor Activity of STP707 IV in Subjects With Solid Tumors

Study Overview
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Brief Summary
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An open label, dose escalation and dose expansion study to evaluate the safety, tolerability, and anti-tumor activity of STP707 with IV administration in subjects with advanced/metastatic or surgically unresectable solid tumors who are refractory to standard therapy.

Detailed Description
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A phase 1, open label, dose escalation and dose expansion study to evaluate the safety, tolerability, and anti-tumor activity of STP707 with IV administration in subjects with advanced/metastatic or surgically unresectable solid tumors who are refractory to standard therapy. The primary objective of this study is to determine the MTD or RP2D of STP707 and to establish the dose of STP707 recommended for future phase 2 studies administered intravenously. A total of 30 subjects will be enrolled in dose escalation. Once MTD or RP2D has been established, up to 10 additional subjects will enrolled to confirm safety and explore anti-tumor activity. Up to 5 dose levels will be explored (3,6,12,24,48 mg dose levels). Intermediate doses between scheduled dose levels maybe explored during escalation. A cycle is 28 days. Dose escalation will follow a standard 3+3 design.

Official Title
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Ph.1, Open-Label, Dose Escalation & Expansion for Safety, Tolerability, PK, & Anti-Tumor Activity of STP707 Administered IV in Subjects With Advanced/Metastatic or Surgically Unresectable Solid Tumors Who Are Refractory to Standard Therapy.

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: STP707
* Drug: STP707
* Drug: STP707
* Drug: STP707
* Drug: STP707


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with histologically or cytologically confirmed advanced / metastatic or surgically unresectable solid tumors whose tumors are refractory to standard therapy Measurable disease per RECIST v 1.1 (primary or metastatic disease) ECOG performance status 0 - 1 Life expectancy of at least 3 months Age ≥18 years Signed, written Institutional Review Board (IRB) approved informed consent A negative serum pregnancy test (for nonsterile women of child-bearing potential) Acceptable liver function: Bilirubin ≤ 1.5 times upper limit of normal AST (SGOT), ALT (SGPT) ≤ 5 times upper limit of normal because of cancer or metastases to the liver Acceptable renal function, defined as: o Serum creatinine ≤ 1.5 ULN or Creatinine Clearance ≥ 50 mL/minute Acceptable hematologic status: Hemoglobin ≥ 9 g/dL (a transfusion is allowed if Hemoglobin stays stable thereafter) Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 Platelet count ≥ 100,000 plt/mm3 x 109/ L Urinalysis with no clinically significant abnormalities Acceptable coagulation status with partial thromboplastin time (PTT) and International Normalized Ratio (INR) ≤ 1.5 times upper limit of normal unless patient is on anticoagulants and has stable PTT and PT that are within normal therapeutic range for disease under management Subject has adequate vitamin D level, as defined by serum total 25-Hydroxyvitamin D [25(OH)D] ≥ 20 to < 60 ng/mL. If subjects are below this threshold, they may receive vitamin D supplementation se per clinic dosing guidelines and may still be enrolled provided they are started on vitamin D supplementation Completion of all previous treatments (including surgery, systemic chemotherapy, and radiotherapy) at least 3 weeks before screening For men and women of child-producing potential, the use of effective contraceptive methods during the study Exclusion Criteria: Baseline Q-T corrected interval (QTc) interval of > 470 msec for all subjects calculated using Fridericia's formula New York Heart Association Class III or IV cardiac disease, or myocardial infarction, severe unstable angina, coronary/peripheral artery bypass graft, congestive heart failure within the past 6 months Known active, uncontrolled infection with HIV or hepatitis B; subjects with hepatitis B allowed if on anti-viral therapy and have a viral load ≤ 500 IU; patients with a history of HIV must be on antiretroviral therapy for at least four weeks and have an HIV viral load ≤ 400 copies/mL, have CD4+ T cell counts ≥ 350 cells/uL and no history of AIDS-defining opportunistic infections within 3 months prior to treatment Major surgical procedure within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure, during the course of the study. (Note: Placement of a central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure.) Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Pregnant or nursing women. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Participation in a clinical study involving administration of an investigational compound within the past 30 days prior to study entry. Unwillingness or inability to comply with procedures required in this protocol Known allergy or hypersensitivity to the study drug(s) or one of the ingredients in the formulation (e.g., Trehalose dihydrate) Existence of any surgical, medical or laboratory condition that, in the judgment of the clinical investigator, might interfere with the safety, distribution, metabolism or excretion of the drug

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: 3+3 design dose escalation followed by
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Arm A<br>Cohort 1: STP707 3 mg dose IV infusion, administered on D1,D8,D15,D22 of a 28-Day cycle. If the patient is deriving clinical benefit from the agent it maybe continued and administered on D1,D8, D15 and D22 for each successive cycle. | Drug: STP707<br>* Investigational Product<br>|
| Experimental: Part 1: Arm B<br>Cohort 2: STP707 6 mg dose IV infusion, administered on D1,D8,D15,D22 of a 28-Day cycle. If the patient is deriving clinical benefit from the agent it maybe continued and administered on D1,D8, D15 and D22 for each successive cycle. | Drug: STP707<br>* Investigational Product<br>|
| Experimental: Part 1: Arm C<br>Cohort 3: STP707 12 mg dose IV infusion, administered on D1,D8,D15,D22 of a 28-Day cycle. If the patient is deriving clinical benefit from the agent it maybe continued and administered on D1,D8, D15 and D22 for each successive cycle. | Drug: STP707<br>* Investigational Product<br>|
| Experimental: Part 1: Arm D<br>Cohort 4: STP707 24 mg dose IV infusion, administered on D1,D8,D15,D22 of a 28-Day cycle. If the patient is deriving clinical benefit from the agent it maybe continued and administered on D1,D8, D15 and D22 for each successive cycle. | Drug: STP707<br>* Investigational Product<br>|
| Experimental: Part 1: Arm E<br>Cohort 5: STP707 48 mg dose IV infusion, administered on D1,D8,D15,D22 of a 28-Day cycle. If the patient is deriving clinical benefit from the agent it maybe continued and administered on D1,D8, D15 and D22 for each successive cycle. | Drug: STP707<br>* Investigational Product<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) | Recommended starting dose & schedule | 28 Day Cycle | 
| Limited Dose Toxicity (LDT) | Recommended starting dose & dose escalation | 28 day cycle |