First-in-Human Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-984 in Combination With Chemotherapy

• Status: Completed
• Trial end date: 2017-10-19
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study was to evaluate the safety and tolerability of VX-984 (M9831) administered alone and in combination with pegylated liposomal doxorubicin (PLD), and to determine the maximum tolerated dose (MTD) and preliminary evidence of efficacy of VX-984 in combination with PLD in participants with advanced solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: EMD Serono Research & Development Institute, Inc.; Vertex Pharmaceuticals Incorporated
• Collaborator: Merck KGaA, Darmstadt, Germany
• Treatments: Doxorubicin; Liposomal doxorubicin

Criteria

Inclusion Criteria:

• Participants (male and female for Part A and female for Part B) were at least 18 year of age.

• Part A Participants with histologically or cytologically confirmed malignant advanced solid tumors, who had progressed on at least 1 prior chemotherapy, and for whom either

1. No standard care available

2. PLD at the dose and schedule being used might be considered standard of care

• Part B

1. Participants with histologically confirmed advanced primary endometrial cancer (locally advanced and incurable endometrial cancer that had been treated with surgery and/or radiation or is ineligible for such treatment), or recurrent or metastatic endometrial cancer, and

2. Completed 1 line of chemotherapy treatment with a platinum-containing regimen in the advanced setting

• Measurable disease according to RECIST criteria (Version 1.1)

• Life expectancy of at least 12 weeks

• Hematological and biochemical indices within acceptable ranges shown at screening.

• Normal left ventricular ejection fraction on screening assessed by transthoracic echocardiogram or multiple gated acquisition (MUGA) scan

Exclusion Criteria:

• Previous radiotherapy (unless brachytherapy), endocrine therapy, chemotherapy, or exposure to investigational medicinal products during the 4 weeks (6 weeks for nitrosoureas and Mitomycin-C) or 4 drug half-lives before the planned administration of the first dose of study drug, whichever is greater. Previous immunotherapy during the 4 weeks before the planned administration of the first dose of study drug.

• For Part B only:

1. Participants with uterine carcinosarcoma

2. Prior anthracycline therapy

3. More than 1 prior chemotherapy regimen (a participant was received first- line carboplatin and taxane and then received the same taxane second- line were considered to have had 1 prior chemotherapy regimen)

• Unresolved toxicity of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater from previous anti-cancer therapy or radiotherapy

• History of spinal cord compression or brain metastases, unless asymptomatic, treated, stable, and not requiring treatment with steroids for at least 4 weeks before the planned administration of the first dose of study drug. Any history of leptomeningeal metastases.

• Female participants who was pregnant or lactating at Screening, or planned to become pregnant while on study or within 6 months after the last dose of study drug

• Female participants of childbearing potential were adhere to contraception guidelines as outlined in the protocol. Female participants were considered to be of nonchildbearing potential if they had undergone surgical hysterectomy or bilateral oophorectomy or had been amenorrheic for more than 2 years with a screening serum follicle-stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females

• Male participants with pregnant or lactating partners or partners who planned to become pregnant while on study or within 6 months after the planned administration of the last dose of study drug

• Major surgery ≤4 weeks before first dose of study drug, or incomplete recovery from a prior major surgical procedure

• Cardiac conditions

• Prior bone marrow transplant

• Extensive radiotherapy (to greater than 15% of bone marrow)

• Any other condition that in the investigator's opinion would not make the participant a good candidate for the clinical study,

• Part B: Current active malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Prior cancer in remission for 2 years or more would not be excluded.