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XL309

Phase 1

Advanced Solid Tumor | Small molecule | Oncology |Exelixis, Inc.|Last Updated: Sep 5, 2025

Target and mechanism

Molecular targetUSP1
Target classInhibitor
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

CONTROLLEDDMC
Total Trials1
Total Enrollment429

FDA Designations

No designations recorded

Clinical trial landscape

XL309 · 1 trial · 1 indication

Phase 1 1
NCT05932862A Phase 1 Study of XL309 (ISM3091) Alone and in Combination in Participants With Advanced Solid TumorsAdvanced Solid Tumor
RECRUITING429 Analytics
PHASE1RECRUITING
A Phase 1 Study of XL309 (ISM3091) Alone and in Combination in Participants With Advanced Solid Tumors
Advanced Solid TumorUnlock trial analytics

Study Endpoints

Primary Endpoints

Dose Escalation Stage: Incidence of TEAEs and SAEs; AEs Leading to Dose Modification, Discontinuation, or Death; and Laboratory Abnormalities
Approximately 24 months

Adverse events will be recorded and severity graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Dose Escalation Stage: Incidence of Dose-Limiting Toxicities (DLTs)
Approximately 24 months
Dose Escalation Stage: XL309 Exposure Over Time Measured as Area Under the Plasma Concentration Curve (AUC)
Approximately 24 months
Dose Escalation Stage: XL309 Maximum Plasma Concentration (Cmax)
Approximately 24 months
Dose Escalation Stage: XL309 Time to Cmax
Approximately 24 months
Dose Escalation Stage: XL309 Trough Concentration (Ctrough)
Approximately 24 months

Lowest concentration of drug in the bloodstream, measured just before the next dose is administered.

Dose Escalation Stage: XL309 Apparent Clearance (CL/F)
Approximately 24 months
Cohort Expansion Stage: Incidence of TEAEs and SAEs; AEs Leading to Dose Modification, Discontinuation, or Death; and Laboratory Abnormalities
Approximately 24 months

Adverse events will be recorded and severity graded using CTCAE version 5.0.

Cohort Expansion Stage: Objective Response Rate (ORR)
Approximately 24 months

ORR will be measured per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by the Investigator. ORR for prostate cancer will be based on Prostate Cancer Working Group 3 (PCWG3) criteria, as assessed by the Investigator

Secondary Endpoints

Dose Escalation Stage: Olaparib Exposure Over Time Measured as Area Under the Plasma Concentration Curve (AUC) at Steady State
Approximately 24 months
Dose Escalation Stage: Olaparib Cmax at Steady State
Approximately 24 months
Dose Escalation Stage: Olaparib Ctrough at Steady State
Approximately 24 months
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Dose Escalation Single Agent EvaluationEXPERIMENTALParticipants will receive XL309 in sequential cohorts of increasing doses.
Dose Escalation Combination TherapyEXPERIMENTALParticipants will receive XL309 in sequential cohorts of increasing doses in combination with olaparib.
Cohort Expansion Stage Single Agent EvaluationEXPERIMENTALThe recommended dose as determined in the Escalation Stage will be further studied in advanced solid tumor-specific cohorts.
Cohort Expansion Stage Combination Therapy EvaluationEXPERIMENTALThe recommended dose as determined in the Escalation Stage will be further studied in combination with olaparib in advanced solid tumor-specific cohorts.

Interventions

NameTypeDescription
XL309DRUGXL309 will be administered orally per assigned schedule.
OlaparibDRUGOlaparib will be administered orally per assigned schedule.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites16

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-Escala...

Countries:United States
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Competitive Landscape -Other Solid Tumors 9 trials (matched to "Advanced Solid Tumor")

Recent Changes (Last 90 Days)

LOWMay 26, 2026NCT05932862primaryCompletionDate: changed
LOWMay 24, 2026NCT05932862studyFirstPostDate: changed

Frequently asked questions about XL309

What is XL309 used for in advanced solid tumors?

XL309 is an investigational small molecule being developed for the treatment of advanced solid tumors. It is currently being studied in a Phase 1 clinical trial in participants with advanced solid tumors, both alone and in combination with other therapies.

What does XL309 target?

XL309 targets USP1, an enzyme involved in DNA repair pathways. As a USP1 inhibitor, it is designed to interfere with tumor cell survival mechanisms, potentially making cancer cells more susceptible to treatment.

Who makes XL309?

XL309 is being developed by Exelixis, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol EXEL. The company is conducting a Phase 1 clinical trial to evaluate the drug in patients with advanced solid tumors.

What phase is XL309 in?

XL309 is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by regulatory authorities and is still being studied for safety and efficacy in patients with advanced solid tumors.

What clinical trials is XL309 in?

XL309 is being studied in a Phase 1 clinical trial with the identifier NCT05932862. This trial is recruiting participants with advanced solid tumors and is being conducted in the United States, with an enrollment target of 429 participants.

Is XL309 the same as ISM3091?

Yes, XL309 is also known as ISM3091. The clinical trial NCT05932862 refers to the drug as XL309 (ISM3091), indicating that both names refer to the same investigational compound being developed for advanced solid tumors.