A Phase 1 Study of XL309 (ISM3091) Alone and in Combination in Patients With Advanced Solid Tumors
Launched by EXELIXIS · Jun 27, 2023
Trial Information
Current as of July 22, 2025
Recruiting
Keywords
ClinConnect Summary
This clinical trial is studying a new drug called XL309, which is being tested alone and in combination with another medication, olaparib, for patients who have advanced solid tumors. The main goals are to see how safe the drug is, how well it works, and how it behaves in the body. The trial is currently recruiting participants aged 18 and older, who are dealing with specific types of cancer such as advanced breast cancer, ovarian cancer, prostate cancer, or pancreatic cancer that have certain genetic characteristics.
To be eligible to participate, patients should have tried standard treatments without success or are not suitable for those treatments. Participants will receive the study drug and will be closely monitored for any side effects or changes in their condition. It’s important to know that certain medical conditions or previous treatments might prevent someone from joining the study, so potential participants should discuss their options with their doctor to see if this trial is a good fit for them.
Gender
ALL
Eligibility criteria
- Key Inclusion Criteria:
- • 1. Capable of understanding and complying with protocol requirements.
- • 2. Male or female aged 18 years or older.
- • 3. Eastern Cooperative Oncology Group performance status 0 or 1.
- • 4. Adequate bone marrow and organ function.
- Dose-Escalation Stage Single Agent and Combination:
- • a) Participants whose tumor progressed, or who were intolerant to standard therapy, have a disease for which no therapy exists or are not a candidate for these therapies, and have one of the following cancers: i. Histologically confirmed locally advanced/metastatic HER2-negative breast cancer, with deleterious or suspected deleterious BRCA1/2 mutation, that progressed on, was intolerant to, was refused, or ineligible for (PARPi).
- • ii. Histologically confirmed locally advanced/metastatic high-grade serous ovarian cancer (HGSOC), including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC). Participants must have progressed on, be intolerant to, or refused PARPi therapy, if PARPi therapy is approved and available in the country where the participant is enrolled.
- • iii. Histologically confirmed locally advanced/metastatic CRPC, with deleterious or suspected deleterious BRCA1/2 mutation, that progressed on, was intolerant to, refused, or ineligible for PARPi.
- • iv. Histologically confirmed locally advanced/metastatic pancreatic cancer with deleterious or suspected deleterious BRCA1/2 mutation that progressed on, was intolerant to, refused, or ineligible for maintenance treatment with a PARPi.
- • v. Locally advanced/metastatic tumors with deleterious or suspected deleterious germline or somatic HRR mutation or HRD phenotype.
- Cohort-Expansion Stage Single Agent and Combination:
- • b) HER2-negative BRCAm Breast cancer cohort: participants with histologically confirmed locally advanced/metastatic HER2-negative Breast cancer with deleterious or suspected deleterious BRCA1/2 mutation and documented radiographic disease progression during or following their last systemic anticancer therapy and who progressed on, was intolerant to, refused, or was ineligible for treatment with a PARPi.
- • c) Platinum-resistant HGSOC cohort: i. Participants with histologically confirmed locally advanced/metastatic HGSOC, including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC), and who progressed on, was intolerant to, refused, or was ineligible for maintenance treatment with a PARPi and who have platinum-resistant disease, defined by platinum free interval of less than 6 months.
- • ii. Platinum-refractory disease (progression on first-line treatment or within 4 weeks of completion) are excluded.
- • d) Platinum-sensitive HGSOC cohort - expansion combination only: histologically confirmed locally advanced/metastatic HGSOC, including PPC and FTC, that progressed on, refused, or ineligible to maintenance treatment with a PARPi, and who have platinum-sensitive disease, defined by platinum free interval of more than 6 months.
- • e) mCRPC cohort: participants with metastatic, castration-resistant adenocarcinoma of the prostate with deleterious or suspected deleterious BRCA1/2 mutation, that progressed on, or was intolerant, refused, or ineligible to PARPi.
- • f) HRRm advanced solid tumors cohort: participants with locally advanced/metastatic tumors with deleterious or suspected deleterious germline or somatic HRR mutation or HRD phenotype.
- For all participants with solid tumors:
- • 5. Participants in the Cohort-Expansion Stage must have at least 1 measurable target lesion.
- • 6. Recovery to baseline or ≤ Grade 1 CTCAE v5 from AE(s) related to any prior treatments.
- • Key Exclusion Criteria
- 1. Prior anticancer treatment including:
- • 1. Small molecule-targeted therapy \< 5 half-lives from first dose of study treatment, or 3 weeks (whichever is shorter).
- • 2. Any antibody therapy \< 5 half-lives from first dose of study treatment (or 4 weeks since last therapy, whichever is shorter).
- • 3. Chemotherapy with nitrosoureas or mitomycin C \< 6 weeks from first dose of study treatment. Other chemotherapy \< 3 weeks prior to first dose of study treatment.
- • 4. Radiation therapy (including radiofrequency ablation) \< 1 week prior to initiation of study treatment. Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible.
- • 2. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment.
- • 3. History of hypersensitivity to any excipient of XL309, or history of allergic reactions attributed to drugs with a similar chemical or biologic structure or class to XL309.
- • 4. Lactating or pregnant females.
- • 5. Clinically relevant cardiovascular disease.
- • 6. Known history of myelodysplastic syndrome.
- • 7. Other severe, acute, or chronic medical condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or that may interfere with the interpretation of the study results, and in the judgment of the investigator, would make the participant inappropriate for the study.
- • 8. Inability or unwillingness to comply with requirement for oral drug administration or presence of a gastrointestinal condition that would preclude adequate absorption of XL309.
About Exelixis
Exelixis, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of cancer. With a commitment to advancing precision medicine, Exelixis leverages its expertise in small molecule drug discovery to address unmet medical needs in oncology. The company's robust pipeline includes a range of investigational compounds targeting various cancer types, supported by rigorous clinical trials that aim to improve patient outcomes. Through collaboration and a patient-centric approach, Exelixis strives to deliver transformative therapies that enhance the quality of life for those affected by cancer.
Contacts
Jennifer Cobb
Immunology at National Institute of Allergy and Infectious Diseases (NIAID)
Locations
Houston, Texas, United States
Houston, Texas, United States
Houston, Texas, United States
Houston, Texas, United States
Houston, Texas, United States
Austin, Texas, United States
Houston, Texas, United States
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San Antonio, Texas, United States
New York, New York, United States
Nashville, Tennessee, United States
Cleveland, Ohio, United States
Orlando, Florida, United States
Kansas City, Missouri, United States
New Brunswick, New Jersey, United States
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Fountain Valley, California, United States
Oklahoma City, Oklahoma, United States
Fountain Valley, California, United States
Jacksonville, Florida, United States
Orlando, Florida, United States
Tampa, Florida, United States
Rochester, Minnesota, United States
Kansas City, Missouri, United States
New Brunswick, New Jersey, United States
New York, New York, United States
Cleveland, Ohio, United States
Oklahoma City, Oklahoma, United States
Germantown, Tennessee, United States
Nashville, Tennessee, United States
Austin, Texas, United States
Houston, Texas, United States
Houston, Texas, United States
San Antonio, Texas, United States
Patients applied
Timeline
First submit
Trial launched
Trial updated
Estimated completion
Not reported