Study of PM54 in Combination With Cytotoxic and Targeted Agents in Adult Participants With Advanced Malignancies

Inclusion Criteria:

* Voluntarily signed and dated written informed consent, obtained before the start of any study-specific procedures.
* Adults greater than or equal to (\>=) 18 years and able to provide free and informed consent for study participation.
* Have a pathologically confirmed diagnosis of 1 of the following (Tumor types have been omitted, as this information is not public.):

Sub- study 1

1. Tumor type, previously treated with 1 to 2 prior lines of therapy for advanced disease, which must have included at least 1 line of platinumbased chemotherapy and programmed cell death protein 1 inhibitor if locally available and approved. All histological subtypes are eligible.
2. Tumor type, previously treated with 1 to 3 prior lines of therapy for advanced disease.
3. Tumor type, previously treated with at least 1 but no more than 2 prior lines of chemotherapy.

Sub- study 2

1. Tumor type, with a maximum of 1 prior line of treatment for advanced disease, and tumor type in Part 2, with no prior treatment for advanced disease.
2. Tumor type, with 2 or 3 prior lines of treatment for advanced disease, which must have included platinum-based chemotherapy and a programmed cell death protein-1 inhibitor. These may have been received as part of a single regimen or in separate regimens.

Note: For the purpose of counting lines of therapy, regimens given as part of multi-modal treatment for localized tumor type (induction/consolidation) are considered 1 line of therapy if disease relapse has occurred during or up to 6 months following treatment discontinuation.

* Have an advanced disease, as defined by progressive, relapsed, or metastatic disease that is not amenable to multimodal ablative or excisional treatments with curative intent, according to international guidelines.
* Have a measurable disease according to RECIST v 1.1. Lesions in areas previously treated with radiation or ablative local therapies must, in addition to measurability requirements defined in RECIST v1.1, only be considered measurable if they experienced documented progression following local treatments.
* Have experienced objective disease progression on or following the last prior line of systemic therapy, as determined either by RECIST v1.1 or equivalent. This does not apply to first-line indications.
* Eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1 at screening.
* Individuals with central nervous system (CNS) metastases are eligible, as long as all of the following are met:

  1. Asymptomatic or minimally symptomatic and stable, with no worsening symptoms in the 4 weeks prior to start of study intervention.
  2. Does not require systemic corticosteroids in excess of an equivalent prednisone dose of 5 milligrams (mg) per day.
  3. Has undergone surgery or radiation and recovered of the effects thereof or are undergoing active surveillance for small-volume CNS metastases with no immediate risk of worsening. A minimum of 2 weeks must have elapsed between the end of radiation treatment and study intervention.
  4. Have not had an epileptic seizure within the 4 weeks prior to start of anticancer treatment and are either free of antiepileptics or on a stable dose prescribed as prophylaxis (as long as no interaction is reported with any of the study drugs).
* Adequate laboratory parameters, as specified below, within 7 days of start of study intervention:

  1. Absolute neutrophil count (ANC) \>=2\*109\^9 per Litre (1/L), platelet count \>=100\*109\^9 per liter, and hemoglobin \>=9 grams per deciliter (g/dL).
  2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to (\<=) 3.0 \* the upper limit of normal (ULN).
  3. Total bilirubin \<=ULN; up to 1.5\*ULN for participants with Gilbert's syndrome.
  4. Creatinine clearance \>=30 milliliters per minute (mL/min), calculated using the cockcroft and gault's formula.
  5. Serum albumin \>=3 g/dL. Albumin infusion to increase the blood level in order to fulfill this inclusion criterion is strictly forbidden.

Sub- study 1

a. Total bilirubin \<= upper limit of normal. Participants with Gilbert's syndrome are not allowed.

* Recovered from the effects of any prior surgery or radiation.
* No ongoing toxicities from prior anticancer treatment of grade greater than (\>) 1 (per national cancer institute common terminology criteria for adverse events \[NCI-CTCAE\] v6.0), except for alopecia and other Grade 2 toxicities that are considered by the investigator to have stabilized/resolved with sequelae and are not at risk of worsening with study intervention. Residual Grade 1 to 2 toxicities from prior immunotherapy - which may include hypo-or hyperthyroidism, type 1 diabetes, hyperglycemia, and adrenal insufficiency - are allowed, if stable and on a stable dose of replacement therapy as applicable.
* Is willing to undergo trial procedures as specified in the protocol, including provision of biologic samples, as well as any study requirements.
* Evidence of nonchildbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure during the course of the trial and up to 7 months after the last study intervention infusion. Fertile male participants with WOCBP partners should use condoms during treatment and for 4 months following the last study intervention infusion.

Exclusion Criteria:

To be eligible for trial participation, individuals must not meet any of the following criteria:

* Prior treatment with PM54 or any other ecteinascidin agent.
* History of hypersensitivity to PM54 or any of the inactive ingredients.
* History of other malignancies within 3 years prior to start of study intervention, except adequately resected non-melanoma skin cancer, low-risk and adequately treated prostate cancer, stage I hormone receptor (HR)-positive breast cancer or other in-situ disease at neglectable risk of relapse.
* Presence of carcinomatous meningitis.
* Participants with clinically significant ascites, defined as any of the following:
* Ascites requiring therapeutic paracentesis or medication (such as diuretics) in the last 4 weeks;
* Moderate or severe ascites on imaging;
* Symptomatic ascites (examples: abdominal distension, discomfort, or dyspnea).
* Presence of any of these medical conditions.

Cardiovascular:

1. History of myocardial, CNS, or other arterial infarction within 6 months before the start of study intervention.
2. Heart failure Class II or higher according to the New York Heart Association or left ventricular ejection fraction less than (\<) 50 percent (%) per echocardiogram or multigated acquisition scan.
3. Symptomatic arrhythmia or other significant electrocardiogram (ECG) abnormalities that in the opinion of the investigator pose an increased risk of complications.
4. Corrected start of the Q wave to the end of the T wave interval (QTc) \>470 milliseconds (ms) on the screening ECG or history of a long QT syndrome.

   Respiratory
5. Severe underlying lung disorder, as per investigator's assessment that can include but not restricted to chronic obstructive pulmonary disease, asthma, restrictive lung disease, or significant pleural effusions not related to the study condition or unlikely to stabilize/benefit with systemic treatment.
6. New onset or worsening of pulmonary embolism or deep vein thrombosis within the previous 2 months, or any history thereof if no stable dose of anticoagulant regimen has been achieved.

   Other
7. Uncontrolled infection requiring antimicrobial agents or unexplained fever within 3 days of the first scheduled day of dosing. Participants with tumor fever may be enrolled if infectious etiology has been adequately ruled out.
8. Prior bone marrow or stem cell transplantation.

Sub- study 1 i. Evidence of Gilbert's syndrome or homozygosity for the UGT1A1\*28 allele. j. Chronic inflammatory bowel disease or intestinal obstruction.

Sub- study 2 k. Patients with Child-Pugh Class C hepatic impairment.

* Has any other medical, behavioral, or social condition that, in the opinion of the investigator, makes the participant ineligible to receive any of the trial treatments cytochrome P450, or undergo key trial procedures.
* Exposure to the products/treatments below, without adequate washout period prior to first dose of study intervention. Note that hormonal therapy received for the adjuvant treatment of tumors at a low risk of relapse is allowed.

Products/treatments and washout periods:

1. Traditional Chinese or herbal medicine with the intent to treat cancer or with known effects on drug metabolism: 2 weeks.
2. Live, attenuated vaccines: 30 days.
3. Chemotherapy: 21 days.
4. Antibodies and antidrug conjugates: 28 days.
5. Targeted agents and small molecules: 2 weeks or 5 half-lives, whichever is longer.
6. Major surgery: 4 weeks. Note: Surgeries typically performed in an outpatient setting are not considered major, even if light sedation or an inpatient stay for oversight was needed.
7. Whole-brain radiation therapy, stereotactic therapy, palliative radiation for symptom control and minor impact on bone marrow: 2 weeks.
8. Other radiation therapy: 4 weeks.
9. Any medication associated with known risk of torsade de pointes: 5 half-lives, except if considered indicated by the investigator, ideally for short duration, under medical monitoring and if no other risk factors for torsade de pointes are present such as prolonged QTc or significant electrolyte abnormalities.
10. Strong or moderate inhibitors of cytochrome P450 3A (CYP3A): 1 week or 5 half-lives, whichever is longer.
11. Strong inducers CYP3A: 2 weeks or 5 half-lives, whichever is longer.
12. P-glycoprotein (P-gp) inhibitors: 2 weeks except for amiodarone, tamoxifen, isavuconazole, and mifepristone (4 weeks).

    Sub- study 1
13. Strong inhibitors or inducers of UGT1A1: 1 week

Sub- study 2

n. CYP2D6 strong inhibitors (bupropion, fluoxetine, paroxetine, quinidine, terbinafine): 1 week or 5 half-lives, whichever is longer.

* Active Human Immunodeficiency Virus (HIV) infection. Inclusion is allowed if:

  1. Undergoing adequate anti-viral treatment and regular clinical oversight with good compliance.
  2. Undetectable HIV viral load.
  3. Cluster of differentiation 4 (CD4) plus (+) lymphocyte count over 350/millimeters to the third power (mm3).
  4. No evidence or suspicion of opportunistic infection.
  5. Antiretroviral medication(s) which is/are not contraindicated. Note: The investigator should obtain and provide the sponsor with written documentation of the above, assessed by a medical doctor experienced in the management of individuals with HIV.
* Individuals with detectable hepatitis C virus (HCV) ribonucleic acid (RNA), which should be tested in case of positive anti-HCV antibody test.
* Positive serology test of hepatitis B surface antigen (HBsAg) with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \>=1000 international unit per milliliter (IU/mL). HBV DNA test is mandatory in case of HBsAg+. Individuals with detectable HBV DNA \<1000 IU/mL or suspected occult HBV infection must undergo prophylaxis of HBV reactivation in order to be eligible.
* Individuals with a short-term risk of anatomic complications from involvement of critical structures such as major vessels, large airways, and vertebral spine.
* Women who are pregnant or breastfeeding and fertile participants (men and women) who are not using a highly effective method of contraception.