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About
The primary objectives of this study are: Part 1 - Vevorisertib as single agent: To assess the safety and tolerability of vevorisertib in participants with advanced solid tumors with v-Akt murine thymoma viral oncogene homolog (AKT) 1, 2, 3 genetic alterations, activating phosphatidylinositol-3-kinase (PI3K) mutations, phosphatase and tensin homolog deleted on chromosome ten (PTEN)-null, or other known actionable PTEN mutations; Part 2 - Vevorisertib in combination with other anti-cancer agents: To assess the safety and tolerability of vevorisertib in combination with paclitaxel or fulvestrant in participants with advanced, inoperable, metastatic and/or recurrent solid tumors with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) / PTEN actionable mutations and/or AKT genetic alterations.
Full description
This study was terminated due to business reasons, and pharmacokinetic (PK) testing was prioritized.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria
Signed written informed consent granted prior to initiation of any study-specific procedures
18 years of age and older
Histologically and/or cytologically documented diagnosis of a selected tumor type that is locally advanced, inoperable, metastatic or recurrent (including but not restricted to breast cancer, TNBC [triple negative]; HR-positive [HR+]/HER2-negative [HER2-] or endometrial cancer)
Documented AKT genetic alterations or known actionable PIK3CA/PTEN mutations by genetic testing
• Participants with tumors with PTEN null/PTEN loss-of-function mutations are not eligible
For combination arms; participants should be eligible for paclitaxel or fulvestrant therapy as per Investigator assessment
Failure to respond to standard systemic therapy, or for whom standard or curative systemic therapy does not exist or is not tolerable
Has at least one measurable target lesion according to RECIST v. 1.1
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1
Adequate organ function as indicated by the following laboratory values. (All laboratory tests must be obtained within 14 days prior to the first dose of study treatment):
Hematological
Renal
Hepatic
Metabolic
If a participant is currently receiving bisphosphonates or any other drug for treatment of osteoporosis, treatment-induced bone loss and metastases to bone, the participant must have received the bisphosphonates for at least four weeks prior to the first dose of study treatment
• Initiation of bisphosphonates or similar agents during the study may be allowed provided the participant completes the first cycle of treatment without any dose limiting toxicity (DLT) and the Investigator rules out tumor progression
Male or female participants of child-producing potential must agree to use adequate contraception, including double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after the last dose of study treatment
Women of childbearing potential must have a negative serum pregnancy test. "Women of childbearing potential" is defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months prior to the first dose of study treatment
Exclusion Criteria
Anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or investigational agents within five half-lives or four weeks, whichever is shorter, prior to administration of the first dose of study treatment
Radiation therapy within four weeks, or palliative radiation therapy within two weeks, prior to administration of the first dose of study treatment
Major surgical procedure within four weeks prior to administration of the first dose of study treatment
• To be eligible for the study treatment, all surgical wounds must be fully healed, and any surgery-related adverse events must recover to Grade ≤ 1.
Unable or unwilling to swallow the complete daily dose of vevorisertib
Previous treatment with
Known prior allergic reaction to or severe intolerance of paclitaxel or fulvestrant. Intolerance is defined as a serious adverse event (AE), a grade 3 or 4 AE per Common Terminology Criteria for Adverse Events (CTCAE) v.4.03, or permanent treatment discontinuation
History of Type 1 diabetes mellitus or Type 2 diabetes mellitus requiring regular medication (other than oral hypoglycemic agents) or fasting glucose ≥ 160 mg/dL at Screening visit
Significant gastrointestinal disorder(s) that could, in the opinion of the Investigator, interfere with the absorption, metabolism, or excretion of vevorisertib (e.g., inflammatory bowel disease, Crohn's disease, ulcerative colitis, extensive gastric resection)
Known untreated or active CNS metastases and/or carcinomatous meningitis
• To be eligible for the study treatment, participants must have stable disease ≥ 1 month, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications
History of myocardial infarction (MI) or New York Heart Association (NYHA) Class II-IV congestive heart failure within 6 months of the administration of the first dose of study treatment (MI occurring > 6 months of the first dose of study treatment will be permitted); Grade 2 or worse conduction defect (e.g., right or left bundle branch block)
A heart rate corrected QT (QTc) interval ≥ 480 msec, using the Fridericia's formula QTcF
Left ventricular ejection fraction (LVEF) <50% as determined by Multiple Gated Acquisition (MUGA) scan or echocardiogram (ECHO) in participants who received prior treatment with anthracyclines
Concurrent severe and/or uncontrolled illness not related to cancer and/or social situation that would limit compliance with study requirements, including but not limited to:
Active or history of other malignancy other than the current cancer within 2 years of the first dose of study treatment, with the exception of carcinoma in-situ of the cervix, basal cell carcinoma, and superficial bladder tumors curatively treated
Blood transfusion or administration of growth factors within 5 days prior to a blood draw being used to confirm eligibility
Pregnant or breastfeeding
Primary purpose
Allocation
Interventional model
Masking
78 participants in 12 patient groups
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Data sourced from clinicaltrials.gov
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