Phase I/​IIa Study of AZD5335 as Monotherapy and Combination Therapy in Participants With Solid Tumors (FONTANA)

• Drug: AZD5335
• Drug: Saruparib (AZD5305)
• Drug: Bevacizumab
• Drug: Carboplatin

Inclusion Criteria:

• Capable of giving signed informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment., 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.
• Consent to provide adequate baseline tumor sample, as applicable per module-specific criteria.
• Participant must be ≥ 18 years at the time of signing the informed consent.
• Willing to provide archival or baseline tumor sample.
• For participants who have previously received targeted therapies such as ADCs, a fresh baseline biopsyremoval of a section of tissue to analyse for cancer cells will be required.
• Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer 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,
  1. A previously irradiated lesion can be considered a target lesion if the lesion is progressing and well defined.
  2. For participants who undergo biopsies at screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer 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 half-lives (45 days) plus 6 months (approximately 7.5 months) following the last dosethe amount of medication taken 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 sperm donation while on study and for 5 half lives (45 days) plus 6 months (~7.5 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 riskthe possibility that something bad will happen 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®, bilateralaffecting both sides 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 5 half-lives (45 days) plus 6 months (In total, 7.5 months) following the last dose of study intervention. It is strongly recommended for the male partner of a female participants to also use 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 refrain from egg donation while on study and for 5 half-lives (45 days) plus 6 months (~7.5 months) following the last dose of study intervention.