Study of PM54 in Combination With Immunotherapy in Adult Participants With Advanced Malignancies

Inclusion Criteria:

1. Voluntarily signed and dated written informed consent, obtained before the start of any study-specific procedures.
2. Adults (greater than or equal to \[\>=\]18 years or legal consenting age, per local regulations), and able to provide free and informed consent for study participation.
3. Have a pathologically confirmed diagnosis of advanced malignancy.
4. Have 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.
5. Have measurable disease according to RECIST1.1 (or mRECIST v1.1 where applicable).
6. Have experienced objective disease progression on or following the prior line(s) of systemic therapy, as determined either by (1) RECIST v1.1 or equivalent, or (2) by investigator's assessment of clinical progression of disease together with objective evidence of increased tumor burden even if not meeting criteria for progressive disease per RECIST v1.1 or equivalent.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 at screening.
8. 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 per day (mg/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 whole-brain 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.
9. Adequate laboratory parameters, as specified below, within 7 days of start of study intervention:

   1. Absolute neutrophil count (ANC) \>=1.5\*10\^9 per liter, platelet count \>=100\*10\^9 per liter, and hemoglobin \>=9 gram 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 \<=1.0\*ULN; up to 1.5\*ULN for participants with Gilbert's syndrome.
   4. Creatinine clearance \>=30 milliliter 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.
   6. Creatine kinase \<=2.5\*ULN.
10. Recovered from the effects of any prior surgery or radiation.
11. No ongoing toxicities from prior anticancer treatment of Grade \>1 (per National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) verison6.0), 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.
12. Is willing to undergo trial procedures as specified in the protocol, including provision of biologic samples, as well as any study restrictions.
13. Evidence of non-childbearing 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:

1. Prior treatment with PM54 or any other ecteinascidin agent, including ecubectedin, trabectedin, and lurbinectedin.
2. History of hypersensitivity to PM54, pembrolizumab, or any of the inactive ingredients.
3. History of other malignancies within 3 years prior to start of study intervention, except adequately resected non-melanoma skin cancer or other in-situ disease at neglectable risk of relapse.
4. Presence of carcinomatous meningitis.
5. 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 \<45 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 QT interval (QTc) \>470 milliseconds (ms) on the screening ECG or history of a long QT syndrome.

      Respiratory
   5. History of interstitial lung disease (ILD) or pneumonitis that have required steroids or other forms of immunosuppression, or any ongoing or suspicion of ILD.
   6. 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.
   7. 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
   8. History of autoimmune or connective tissue disease that (a) in the opinion of the investigator may have a significant risk of worsening with study intervention or (b) has a history or risk of significant mg/day of prednisone equivalent or other systemic immunosuppressants in the previous 1 year to control a disease flare.
   9. 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. j. Prior bone marrow or stem cell transplantation.
6. Has any other medical, behavioral, or social condition that, in the opinion of the investigator, makes the participant ineligible to receive PM54, pembrolizumab, or undergo key trial procedures.
7. Exposure to the anticancer 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: 28 days.
   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 increased risk of torsade de pointes, 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.: 5 half-lives.
   10. Strong or moderate inhibitors or inducers of cytochrome (CYP) 3A4: 2 weeks.
   11. Corticosteroids: must be \<= 10 mg/day of prednisone equivalent within 3 days of start of study intervention. The investigator is encouraged to review indication for ongoing use of corticosteroids and consider de-escalation or interruption if appropriate.
8. Active HIV infection. Inclusion is allowed if:

   1. Undergoing adequate anti-viral treatment and regular clinical oversight with good compliance.
   2. Undetectable human immunodeficiency virus (HIV) viral load.
   3. CD4+ lymphocyte count over 350 per millimeter cube.
   4. No evidence or suspicion of opportunistic infection. 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.
9. Individuals with detectable hepatitis C virus (HCV) ribonucleic acid (RNA), which should be tested in case of positive anti-HCV antibody test.
10. Positive serology test of hepatitis B surface antigen (HBsAg) with hepatitis B virus (HBV) DNA \>= 1000 International Units per milliliter (IU/mL). Hepatitis B virus (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.
11. Individuals with a short-term risk of anatomic complications from involvement of critical structures such as major vessels, large airways, and vertebral spine.
12. Women who are pregnant or breastfeeding and fertile participants (men and women) who are not using a highly effective method of contraception (see inclusion criterion No. 13).