Trial Title:
A Phase 1 Study of XL309 (ISM3091) Alone and in Combination in Patients With Advanced Solid Tumors
NCT ID:
NCT05932862
Condition:
Advanced Solid Tumor
Conditions: Official terms:
Neoplasms
Olaparib
Conditions: Keywords:
breast cancers
ovarian cancer
prostate cancer
Advanced HRD Solid Tumors
pancreatic cancer
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
XL309 (ISM3091)
Description:
XL309 will be administered orally once daily.
Arm group label:
Cohort Expansion Stage Combination Therapy Evaluation
Arm group label:
Cohort Expansion Stage Single Agent Evaluation
Arm group label:
Dose Escalation Combination Therapy
Arm group label:
Dose Escalation Single Agent Evaluation
Intervention type:
Drug
Intervention name:
Olaparib
Description:
Olaparib administered orally twice daily.
Arm group label:
Cohort Expansion Stage Combination Therapy Evaluation
Arm group label:
Dose Escalation Combination Therapy
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.
Criteria for 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) 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Exelixis Clinical Site 12
Address:
City:
Fountain Valley
Zip:
92708
Country:
United States
Status:
Recruiting
Facility:
Name:
Exelixis Clinical Site 8
Address:
City:
Orlando
Zip:
32827
Country:
United States
Status:
Recruiting
Facility:
Name:
Exelixis Clinical Site 10
Address:
City:
Kansas City
Zip:
64111
Country:
United States
Status:
Recruiting
Facility:
Name:
Exelixis Clinical Site 9
Address:
City:
New Brunswick
Zip:
08901
Country:
United States
Status:
Recruiting
Facility:
Name:
Exelixis Clinical Site 5
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Recruiting
Facility:
Name:
Exelixis Clinical Site 7
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Status:
Recruiting
Facility:
Name:
Exelixis Clinical Site 11
Address:
City:
Germantown
Zip:
38138
Country:
United States
Status:
Recruiting
Facility:
Name:
Exelixis Clinical Site 6
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Facility:
Name:
Exelixis Clinical Site 4
Address:
City:
Austin
Zip:
78758
Country:
United States
Status:
Recruiting
Facility:
Name:
Exelixis Clinical Site 1
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Facility:
Name:
Exelixis Clinical Site 2
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Withdrawn
Facility:
Name:
Exelixis Clinical Site 3
Address:
City:
San Antonio
Zip:
78229
Country:
United States
Status:
Recruiting
Start date:
August 17, 2023
Completion date:
August 3, 2029
Lead sponsor:
Agency:
Exelixis
Agency class:
Industry
Source:
Exelixis
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05932862
