A Phase 1 Study of XL309 (ISM3091) Alone and in Combination in Patients With Advanced Solid Tumors

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05932862
• Other study ID #: XL309-101
• Status: Recruiting
• Phase: Phase 1
• Start date: August 17, 2023
• Est. completion date: August 3, 2029

Study information

• Verified date: June 2024
• Source: Exelixis
• Contact: Exelixis Clinical Trials
• Phone: 1-888-393-5494)
• Email: druginfo[@]exelixis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a FIH, multicenter, open-label Phase I study to investigate the safety, tolerability, preliminary antitumor activity, as well as PK and pharmacodynamics of XL309 (previously ISM3091) administered alone or in combination with olaparib in subjects with advanced solid tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 377
• Est. completion date: August 3, 2029
• Est. primary completion date: January 3, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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) Subjects who relapsed, progressed, or were intolerant to standard therapy, have a disease for which no therapy with a known overall survival benefit 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 HGSOC (high-grade serous ovarian cancer), including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC), that progressed on, was intolerant to, refused, or ineligible to maintenance treatment with a PARPi.

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: i. Histologically confirmed locally advanced/metastatic HER2-negative Breast cancer with deleterious or suspected deleterious BRCA1/2 mutation have documented radiographic disease progression during or following their last systemic anticancer therapy and that progressed on, was intolerant to, refused, or ineligible for treatment with a PARPi.

c) Platinum-resistant HGSOC cohort: i. Histologically confirmed locally advanced/metastatic HGSOC, including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC), that progressed on, was intolerant to, refused, or ineligible to 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: i. 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: i. Subjects 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: i. Locally advanced/metastatic tumors with deleterious or suspected deleterious germline or somatic HRR mutation or HRD phenotype.

For all subjects with solid tumors:

5. Subjects 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. Chemotherapy or small molecule-targeted therapy < 3 weeks prior to first dose of study treatment.

2. Any antibody therapy < 5 half-lives from first dose of study treatment (or 4 weeks since last therapy, whichever is the shortest).

3. Chemotherapy with nitrosoureas or mitomycin C < 6 weeks from first dose of study treatment.

4. Radiation therapy (including radiofrequency ablation) < 1 week prior to initiation of study treatment. Subjects 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 judgement of the investigator, would make the patient 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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Drug:
• XL309 (ISM3091)
XL309 will be administered orally once daily.
• Olaparib
Olaparib administered orally twice daily.

Locations

Country	Name	City	State
United States	Exelixis Clinical Site 4	Austin	Texas
United States	Exelixis Clinical Site 1	Houston	Texas
United States	Exelixis Clinical Site 2	Houston	Texas
United States	Exelixis Clinical Site 6	Nashville	Tennessee
United States	Exelixis Clinical Site 5	New York	New York
United States	Exelixis Clinical Site 3	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation Stage Primary Objectives/Outcome 1	To assess the safety and tolerability and to establish a preliminary RD of XL309 as monotherapy and in combination. Incidence of dose-limiting toxicities (DLTs).	Approximately 24 months
Primary	Dose Escalation Stage Primary Objectives/Outcome 2	Incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs). AEs and SAEs that lead to any dose modification, AEs and SAEs leading to discontinuation or deaths.	Approximately 42 months
Primary	Dose Escalation Stage Primary Objectives/Outcome 3	PK parameters, including AUC, Cmax, Tmax, clearance, Cmin.	Approximately 42 months
Primary	Dose Expansion Stage Primary Objectives/Outcome 1	To further assess the safety and tolerability of XL309 as monotherapy and in combination.; To assess preliminary efficacy of XL309 as monotherapy and in combination.	Approximately 42 months
Primary	Dose Expansion Stage Primary Objectives/Outcome 2	Incidence of treatment-emergent AEs, SAEs, AEs and SAEs leading to dose reduction, delay, discontinuation or deaths.	Approximately 42 months
Primary	Dose Expansion Stage Primary Objectives/Outcome 3	ORR per PCWG3 criteria for prostate cancer and RECIST version 1.1 for all other solid tumors as assessed by Investigator.	Approximately 42 months
Secondary	Dose Escalation Stage Secondary Objectives/Outcome 1	To characterize the PK of XL309 alone and when given in combination following a single dose administration and at a steady state after multiple dosing.	Approximately 42 months
Secondary	Dose Escalation Stage Secondary Objectives/Outcome 2	Concentration of XL309 agent and olaparib in plasma at specified time points	Approximately 42 months
Secondary	Dose Expansion Stage Secondary Objectives/Outcome 1	To characterize the PK of XL309 alone and when given in combination following a single dose administration and at a steady state after multiple dosing.	Approximately 42 months
Secondary	Dose Expansion Stage Secondary Objectives/Outcome 2	Concentration of XL309 and olaparib in plasma at specified time points.	Approximately 42 months