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

Inclusion Criteria:

- Subjects (male and female for Part A and female for Part B) will be at least 18 year
of age.

- Part A Subjects with histologically or cytologically confirmed malignant advanced
solid tumors, who have 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. Subjects with histologically confirmed advanced primary endometrial cancer
(locally advanced and incurable endometrial cancer that has 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. Subjects with uterine carcinosarcoma

2. Prior anthracycline therapy

3. More than 1 prior chemotherapy regimen (a subject who received first- line
carboplatin and taxane and then receives the same taxane second- line will be
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 subjects who are pregnant or lactating at Screening, or plan to become pregnant
while on study or within 6 months after the last dose of study drug

- Female subjects of childbearing potential must adhere to contraception guidelines as
outlined in the protocol. Female subjects will be considered to be of nonchildbearing
potential if they have undergone surgical hysterectomy or bilateral oophorectomy or
have 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 subjects with pregnant or lactating partners or partners who plan 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 subject 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.