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Testing XL309 alone and with olaparib in patients with advanced solid tumors

An Open-Label, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of XL309 (ISM3091) as Single-Agent and Combination Therapy in Patients With Advanced Solid Tumors

Phase 1 Interventional Exelixis · NCT05932862

This study is testing a new treatment called XL309, both alone and with another drug called olaparib, to see if it can help people with advanced solid tumors like breast and ovarian cancer who haven't had success with other therapies.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment429 (estimated)
Ages18 Years and up
SexAll
SponsorExelixis Industry-sponsored
Drugs / interventionsChemotherapy, Radiation
Locations16 sites (Fountain Valley, California and 15 other locations)
Trial IDNCT05932862 on ClinicalTrials.gov

What this trial studies

This Phase 1 study aims to evaluate the safety and tolerability of XL309 (ISM3091) both as a standalone treatment and in combination with olaparib in patients suffering from advanced solid tumors. The study will assess preliminary antitumor activity, pharmacokinetics, and pharmacodynamics of the treatments. Participants will include those whose tumors have progressed or who are intolerant to standard therapies, focusing on specific types of cancer such as breast and ovarian cancer.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced solid tumors, specifically those who have progressed on or are intolerant to existing therapies.

Not a fit: Patients with early-stage cancers or those who have not yet undergone standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors who have limited therapeutic alternatives.

How similar studies have performed: Other studies have shown promise with similar approaches, particularly in targeting advanced solid tumors with novel agents.

Eligibility criteria

Show full inclusion / exclusion 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.
5. Participant-disease Characteristics

   Dose-Escalation Stage Single Agent and Combination:

   a) Participants whose tumor progressed on, 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 human epidermal growth factor receptor-2 (HER2)-negative breast cancer, with deleterious or suspected deleterious breast cancer gene (BRCA)1/2 alteration.

   ii. Histologically confirmed locally advanced/metastatic high-grade serous ovarian cancer (HGSOC), including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC).

   iii. Histologically confirmed locally advanced/metastatic CRPC, with deleterious or suspected deleterious BRCA1/2 alteration.

   iv. Histologically confirmed locally advanced/metastatic pancreatic cancer with deleterious or suspected deleterious BRCA1/2 alteration.

   v. Locally advanced/metastatic tumors with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) mutation or homologous recombination deficiency (HRD) phenotype.

   Cohort-Expansion Stage Single Agent and Combination:

   b) HER2-negative breast cancer cohort: participants with histologically confirmed locally advanced/metastatic (HER2)-negative breast cancer with alterations in select HRR genes.

   c) Platinum-sensitive HGSOC cohort: participants with histologically confirmed locally advanced/metastatic HGSOC, including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC), with positive HRD result using an approved diagnostic, and/or alterations in select HRR genes.

   d) mCRPC cohort: participants with metastatic, castration-resistant adenocarcinoma of the prostate with alterations in select HRR genes.

   e) HRRm advanced solid tumors cohort: participants with locally advanced/metastatic tumors with alterations in select HRR genes.

   For all participants with solid tumors:
6. Participants in the Cohort-Expansion Stage must have at least 1 measurable target lesion.
7. 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.
9. Prior treatment with a ubiquitin specific peptidase 1 (USP1) inhibitor.

Where this trial is running

Fountain Valley, California and 15 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Solid TumorOvarian CancerProstate CancerPancreatic CancerAdvanced HRRm Solid TumorsBreast Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.