This drug-drug interaction (DDI) study aims to evaluate the impact of pelabresib at steady-state plasma concentrations on the pharmacokinetic (PK) profile of A) a single dose of repaglinide and a single dose of midazolam, and B) a single dose of combined drospirenone and ethinyl estradiol. The study will be conducted in adult participants with advanced malignancies for whom no standard or curative treatment options are available.

This clinical study is divided into two components:

1. Part 1: Interventional Phase This phase evaluates the drug-drug interaction (DDI) potential of pelabresib with specific victim drugs.

   • Arm A: Assesses pelabresib's DDI potential with repaglinide and midazolam. Participants will be hospitalized for two nights-one starting on Pre-cycle Day 1 and another on Day 14. Beginning Cycle 1 Day 1, participants will receive 225 mg of pelabresib daily for 14 days, followed by a 7-day break.
   • Arm B: Evaluates pelabresib's DDI potential with drospirenone and ethinyl estradiol. Hospitalization will range from a minimum of 2 nights to a maximum of 10 nights-up to 5 nights starting on Pre-cycle Day 1, and up to 5 nights starting on Cycle 1 Day 10. Participants will follow the same pelabresib dosing schedule as Arm A. Arm B will proceed independently of Arm A's results.

2. Part 2: Continued Treatment Phase Participants demonstrating clinical benefit, as determined by the investigator, may continue receiving pelabresib in additional treatment cycles.

A participant is considered to have entered the screening period upon signing the informed consent form. Enrollment occurs when the participant is assigned their first dose of study treatment via the IRT system. Completion is defined as having finished all study phases, including the End of Treatment (EOT) and the 30-day Safety Follow-Up visits. Participants with hematological malignancies will continue follow-up every 3 months after EOT.

1. End of Treatment Visit Must occur within 7 days of the last pelabresib dose or within 7 days of the decision to discontinue treatment, if that decision is made more than 7 days after the last dose.
2. 30-Day Safety Follow-Up All participants will be monitored for adverse events (AEs) and serious adverse events (SAEs) for 30 ± 3 days after the final pelabresib dose. If a participant initiates another anticancer therapy or transitions to pelabresib via another source (e.g., extension study or commercial supply), safety follow-up ends at the start of the new treatment.
3. Leukemic Transformation Monitoring Participants with hematological malignancies will be followed every 3 months after EOT for signs of leukemic transformation, continuing until one of the following: study end, confirmation of acute myeloid leukemia (AML), withdrawal of consent, loss to follow-up, or death.

Key Inclusion Criteria:

Key inclusion criteria for all participants (Arm A and Arm B)

• Is at least 18 years of age at the time of signing the informed consent.

• Has a confirmed documented diagnosis of an advanced malignancy for which no standard and/or curative treatment options are available

• Has the following acceptable laboratory assessments prior to the first dose of study treatment:

  1. Platelet count ≥ 150 × 109 /L in the absence of thrombopoietic factors or transfusions within 2 weeks of the screening assessment
  2. Absolute neutrophil count (ANC) ≥ 1 × 109 /L in the absence of granulocyte growth factors
  3. Peripheral blood blast count < 5%. Assessment of blasts in bone marrow is not mandatory at screening; however, blasts must be <5% if the bone marrow assessment is performed.
  4. Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN)
  5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN (≤5 × ULN if the elevation can be ascribed to liver involvement)
  6. Calculated or measured creatinine clearance of ≥30 mL/min*

• Has fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy (residual Grade 1 toxicities and residual alopecia of any grade are allowed).

Additional inclusion criterion for Arm B

• Is a female participant.

Key Exclusion Criteria:

Key exclusion criteria for Arm A

• Has a history of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical class.
• Is pregnant (confirmed by a pregnancy test at screening) or is breastfeeding.
• Has current known active or chronic infection with HIV, hepatitis B, or hepatitis C.
• Has impaired cardiac function or clinically significant cardiac disease.
• Has a gastrointestinal tumor, impaired GI function, GI disease, or significant resection of stomach or other portion of the gastrointestinal tract that could alter the absorption of pelabresib, midazolam, or repaglinide, including any unresolved nausea, vomiting, or diarrhea.

Key exclusion criteria for Arm B

• Has renal impairment (CrCl less than 50 mL/min).
• Has a gastrointestinal tumor, impaired GI function, GI disease, or significant resection of stomach or other portion of the gastrointestinal tract that could alter the absorption of pelabresib, drospirenone and ethinyl estradiol, including any unresolved nausea, vomiting, or diarrhea.
• Has breast cancer or other estrogen- or progestin-sensitive cancer.
• Has undiagnosed abnormal uterine bleeding.

Other protocol-defined inclusion/exclusion criteria may apply.