PQ203 in Advanced Malignant Tumors Including Triple Negative Breast Cancer

Inclusion Criteria:

* At least 18 years old
* Histologically or cytologically documented metastatic or locally advanced solid tumor malignancies having progressed through or being otherwise ineligible to receive approved standard-of-care therapies
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
* Documented presence of RECIST v1.1 measurable disease
* Adequate organ function confirmed by the following laboratory values obtained within 14 days of the first dose of PQ203:

Bone Marrow Function

* Absolute neutrophil count (ANC) ≥ 1.5 × 10e9/L
* Platelets \> 100 × 10e9/L
* Hemoglobin ≥ 9 g/dL

Hepatic Function

* AST, alanine transaminase ALT or ALP ≤ 2.5 × upper limit of normal (ULN); if liver metastases, then ≤ 5 × ULN
* Bilirubin ≤ 1.5 × ULN (\< 2 × ULN if hyperbilirubinemia is due to Gilbert's syndrome)
* Serum albumin ≥ 35 g/L (3.5 g/dL)

Renal Function

* Calculated creatinine clearance of ≥ 60 mL/min by the Cockcroft-Gault equation
* Urine protein \< 2+

Cardiac Function

• Left ventricular ejection fraction (LVEF) ≥ 50%

Other

* Understand and voluntarily sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)/Research Ethics Board (REB)-approved informed consent form prior to any study-specific evaluation.
* PT/PTT or INR \<1.2x upper limit of normal
* Non-surgically sterile men and women of child bearing potential must agree to use highly effective methods of contraception for at least 4 months beyond the final dose received.
* Toxicity of previous antitumor therapy has returned to Grade ≤1

Exclusion Criteria:

* Patients with primary central nervous system (CNS) malignancies (Patients with stable brain metastases (≥ 4 weeks after a treatment) not requiring steroids or other treatment will be allowed on study).
* Blood transfusion within 14 days of study treatment
* Serious comorbid medical conditions such as heart, lung, kidney, liver, and brain disease that, in the opinion of the enrolling investigator, could interfere with study treatment
* Subjects with history of severe heart disease
* QTc interval using Fridericia's formula (QTcF) \> 470 ms
* Estimated or known weight \> 115 kg (253 lbs)
* Known/suspected pregnancy and/or lactation
* Diastolic blood pressure \< 60 mmHg or \>110 mmHg
* Uncontrolled intercurrent illness
* Long term care facility resident or prisoner
* Any prior receipt of a MMAE-containing drug
* Any prior receipt of a SORT1-targeting medication
* Participation in another clinical study investigating a drug or medical device or a neuro-interventional or surgical procedure that is not considered as standard care in the 30 days preceding study enrolment
* Treatment with any of the following:
* Chemotherapy or other systemic anti-cancer therapy ≤14 days or 5 half-lives (whichever is shorter) prior to first dose of study drug except for Nitrosoureas or mitomycins ≤42 days
* Major surgery ≤28 days from first dose of study drug
* Patients with a history of cerebrovascular accident within 6 months of planned first dose.
* Patients with clinically symptomatic ocular toxicities
* Patients with history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that require steroids, with current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
* Patients with active Grade \>1 peripheral neuropathy