Core Inclusion Criteria:
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative. Participants who do not provide informed consent for Optional Genetic Research may still be enrolled in the study.
- Participant must be ≥ 18 years at the time of signing the informed consent.
- Willing to provide adequate archival and/or baseline tumor sample as applicable per module-specific criteria.
- For participants who have previously received targeted therapies such as ADCs, a fresh baseline biopsy will be required unless the most recent archival tissue sample was collected after receipt of such treatment.
- Eastern Cooperative Oncology Group Performance Status of 0 or 1.
- Participants with advanced solid tumors must have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease, or, in the opinion of the Investigator, a clinical trial is the best option for the next treatment based on response and/or tolerability to prior therapy. Participants with contraindications or who refuse therapy in accordance with local practice may also be considered provided that it is documented that he/she was informed about all therapeutic options.
- Participants must have measurable disease per RECIST v1.1,
- A previously irradiated lesion can be considered a target lesion if the lesion is progressing and well defined.
- For participants who undergo biopsies at screening and/or on treatment, it is preferred though not required, that the biopsied lesion, be distinct from any target lesion used in the RECIST v1.1 evaluation.
- Life expectancy ≥ 12 weeks.
- Adequate organ and marrow function.
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
(a) Male participants: (i) Male participants who are sexually active with a female partner of childbearing potential must use a male condom (plus an additional contraceptive method) post-screening through 5 months following the last dose of study intervention. It is strongly recommended for the female partner of a male participant to also use a highly effective method of contraception throughout this period. In addition, male participants must refrain from freezing or donating sperm while on study and for 5 months following the last dose of study intervention.
(b) Female participants: (i) Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study intervention and a negative urine or serum pregnancy test prior to starting their next cycle of treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
(ii) (ii) Sex and Contraceptive/Barrier Requirements: Highly effective birth control methods include: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) [(periodic abstinence e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contraception], a vasectomized partner, Implanon®, bilateral tubal occlusion, intrauterine device/levonorgestrel intrauterine system, Depo Provera™ injections, oral contraceptive associated with inhibition of ovulation, and Evra Patch™, Xulane™, or NuvaRing®.
Female participants of childbearing potential who are sexually active with a non-sterilized male partner must agree to use one highly effective method of birth control (defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly), from enrolment throughout the study and for 8 months following the last dose of study intervention. The male partner of a female participant of childbearing potential must also use a male condom (plus spermicide, if available) throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. In addition, female participants must not donate or retrieve for their own use, ova while on study and for 8 months following the last dose of study intervention.
Core Exclusion Criteria:
- Patients with spinal cord compression or a history of leptomeningeal carcinomatosis.
- Patients with brain metastases unless, asymptomatic, stable, and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 4 weeks prior to first dose of study intervention.
- Treatment with any of the protocol defined medications, without adequate washout periods or time before the first dose of study intervention.
- Unresolved toxicities of Grade ≥ 2 (National Cancer Institute [NCI] CTCAE v5.0) from prior therapy (excluding vitiligo, alopecia, and endocrine disorders that are controlled with replacement hormone therapy). Participants with stable ≤ Grade 2 neuropathy are eligible.
- Active infection, including tuberculosis and infections with hepatitis B virus (HBV; verified by known positive hepatitis B surface antigen [HBsAg] result), hepatitis C virus (HCV) or known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA, CD4+ count ≥ 350/mm3, no history of acquired immune deficiency syndrome-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications (meaning there are no expected further changes in that time to the number or type of antiretroviral drugs in the regimen).
Patients with a past or resolved HBV/HCV infection are eligible if:
- Negative for HBsAg and positive for anti-hepatitis B virus core protein (HBc) or
- Are HBsAg + with chronic HBV infection (lasting 6 months or longer) and meet conditions i-iii below:
(i) HBV DNA viral load <100 IU/mL. (ii) Have normal transaminase values, or, if liver metastases are present, abnormal transaminases, with a result of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) <3 x upper limit of normal (ULN), which are not attributable to HBV infection.
(iii) Start or maintain antiviral treatment if clinically indicated as per the Investigator or as per local guideline.
Note for Japan: Japanese patients with positive anti-HBs/anti-HBc and negative HBsAg will be assessed following local guidelines.
(c) Participants testing positive for HCV antibody are eligible only if the polymerase chain reaction test result is negative for HCV RNA.