Study of XL102 as Single-Agent and Combination Therapy in Subjects With Solid Tumors (QUARTZ-101)

Sponsor

Exelixis (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04726332

Collaborator

(none)

298

Enrollment

Locations

Arms

43.7

Anticipated Duration (Months)

59.6

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1, open-label, dose-escalation and expansion study evaluating the safety, tolerability, PK, antitumor activity, and effect on biomarkers of XL102 administered orally alone and in multiple combination regimens to subjects with advanced solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Neoplasm Malignant Epithelial Ovarian Cancer Triple Negative Breast Cancer Hormone Receptor Positive Breast Carcinoma Metastatic Castration-resistant Prostate Cancer	Drug: XL102 Drug: Fulvestrant Drug: Abiraterone Drug: Prednisone	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

298 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

single-agent and combination therapy dose-escalation followed by cohort-expansionsingle-agent and combination therapy dose-escalation followed by cohort-expansion

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Dose Escalation and Expansion Study of the Safety and Pharmacokinetics of XL102 as Single-Agent and Combination Therapy in Subjects With Inoperable Locally Advanced or Metastatic Solid Tumors

Actual Study Start Date :

Feb 10, 2021

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: XL102 Single-Agent Dose-Escalation Cohorts Subjects (Cohort A) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.	Drug: XL102 oral doses of XL102
Experimental: XL102 Single-Agent Expansion Cohorts The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with triple-negative breast cancer (TNBC) (Cohort D), epithelial ovarian cancer (EOC) (Cohort E), hormone receptor-positive breast cancer (HR+ BC) (Cohort F), and metastatic castration-resistant prostate cancer (mCRPC) (Cohort G).	Drug: XL102 oral doses of XL102
Experimental: XL102 + Fulvestrant Dose-Escalation Cohorts Subjects with HR+ BC (Cohort B) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.	Drug: XL102 oral doses of XL102 Drug: Fulvestrant fulvestrant 500 mg administered as an intramuscular (IM) injection every 2 weeks for the first 3 doses and then every 4 weeks.
Experimental: XL102 + Abiraterone/Prednisone Dose-Escalation Cohorts Subjects with mCRPC (Cohort C) will accrue in cohorts of 3-12 subjects in a modified i3+3 design.	Drug: XL102 oral doses of XL102 Drug: Abiraterone abiraterone 1000 mg administered orally once daily. Drug: Prednisone prednisone 5 mg administered orally twice daily.
Experimental: XL102 + Fulvestrant Expansion Cohorts The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with HR+ BC (Cohort H).	Drug: XL102 oral doses of XL102 Drug: Fulvestrant fulvestrant 500 mg administered as an intramuscular (IM) injection every 2 weeks for the first 3 doses and then every 4 weeks.
Experimental: XL102 + Abiraterone/Prednisone Expansion Cohorts The MTD or recommended dose from the dose-escalation stage may be further explored in subjects with mCRPC (Cohort I).	Drug: XL102 oral doses of XL102 Drug: Abiraterone abiraterone 1000 mg administered orally once daily. Drug: Prednisone prednisone 5 mg administered orally twice daily.

Outcome Measures

Primary Outcome Measures

Dose-Escalation Stage: MTD/recommended dose for XL102 [Approximately 18 months]
To determine the MTD and/or RD for further evaluation of XL102 when administered orally alone and in combination therapy in subjects with advanced solid tumors
Cohort-Expansion Stage: Objective Response Rate (ORR) [Approximately 12 months]
To evaluate preliminary efficacy of XL102 when administered alone and in combination therapy by estimating the ORR as assessed by the Investigator per RECIST 1.1

Secondary Outcome Measures

Safety of XL102 as evaluated by Incidence and Severity of Adverse Events (AEs) [Approximately 30 months]
To evaluate the safety of XL102 when administered orally alone and in combination therapy through the evaluation of overall incidence of AEs, severity grade, relationship to study treatment, and laboratory tests.
Tolerability of XL102 as evaluated by Study Treatment Exposure, Dose Intensity and Modifications, and Study Treatment Discontinuation due to AE [Approximately 30 months]
To evaluate the tolerability of XL102 when administered orally alone and in combination therapy through the evaluation of study treatment exposure, dose intensity, dose modifications, and study treatment discontinuation due to AE.
Dose-Escalation Stage: Drug-Drug Interactions [Approximately 18 months]
To assess drug-drug interactions between XL102 and combination agents
Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax) [Approximately 18 months]
To evaluate the Tmax of XL102 alone and in combination therapy
Dose-Escalation Stage: Maximum Plasma Concentration (Cmax) [Approximately 18 months]
To evaluate the Cmax of XL102 alone and in combination therapy
Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24) [Approximately 18 months]
To evaluate the AUC 0-24 of XL102 alone and in combination therapy
Dose-Escalation Stage: Terminal Half-Life [Approximately 18 months]
To evaluate the terminal half-life of XL102 alone and in combination therapy
Dose-Escalation Stage: Apparent Clearance (CL/F) [Approximately 18 months]
To evaluate the CL/F of XL102 alone and in combination therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Cytologically or histologically and radiologically confirmed solid tumor that is inoperable, locally advanced, metastatic, or recurrent.
Dose-Escalation Stage Cohort A (Solid Tumors): The subject has a solid tumor that is unresectable or metastatic and for which life-prolonging measures do not exist or available therapies are intolerable or no longer effective.
Dose-Escalation Stage Cohort B and Cohort-Expansion Stage Cohorts F and H (Hormone Receptor-Positive Breast Cancer): Subjects with breast cancer that is hormone receptor-positive (estrogen receptor positive [ER+] and/or progesterone receptor positive [PR+]) and negative for human epidermal growth factor receptor 2 (HER-2 negative [HER-2-]) and who have documented radiographic disease progression during or following their last systemic anticancer therapy for inoperable locally advanced or metastatic disease.
Dose-Escalation Stage Cohort C and Cohort-Expansion Stage Cohorts G and I (Metastatic Castration-Resistant Prostate Cancer): Subjects with adenocarcinoma of the prostate. Note: Neuroendocrine differentiation and other histological features are permitted if adenocarcinoma is the primary histology.
Cohort-Expansion Stage Cohort D (Triple Negative Breast Cancer): Subjects with breast cancer that is negative for HER-2, estrogen receptors, and progesterone receptors, and who have documented radiographic disease progression during or following their last systemic anticancer therapy for inoperable locally advanced or metastatic disease.
Cohort-Expansion Stage Cohort E (Epithelial Ovarian Cancer): Subjects with epithelial ovarian cancer, including primary peritoneal cancer (PPC) and fallopian tube cancer (FTC) who have platinum-resistant disease following treatment with a platinum-containing chemotherapy. Ovarian borderline epithelial tumors (low malignant potential) are excluded.
Expansion Cohorts: Subjects must have measurable disease per RECIST 1.1 as determined by the Investigator.
Tumor tissue material (archival or fresh tumor tissue [if it can be safely obtained]).
Recovery to baseline or ≤ Grade 1 severity (Common Terminology Criteria for Adverse Events version 5 [CTCAE v5]) from AEs.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
Adequate organ and marrow function.
Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception.
Female subjects of childbearing potential must not be pregnant at screening.

Exclusion Criteria:

Receipt of XL102 or any other selective CDK7 inhibitor.
Receipt of any cytotoxic chemotherapy therapy or anticancer antibody therapy within 21 days before first dose of study treatment.
Receipt of any type of small molecule kinase inhibitor within 2 weeks before first dose of study treatment.
Receipt of any anticancer hormonal therapy within 2 weeks or within 5 half-lives of the agent, whichever is shorter, before first dose of study treatment.
HR+BC subjects enrolled in the Combination Cohorts B and H receiving fulvestrant prior to first dose of study treatment are allowed to continue with their fulvestrant treatment.
Metastatic CRPC subjects enrolled in the Combination Cohorts C and I receiving abiraterone prior to first dose of study treatment are allowed to continue with their abiraterone treatment.
Radiation therapy within 14 days before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
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.
Concomitant use of certain medications.
Uncontrolled, significant intercurrent or recent illness.
Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG).
Pregnant or lactating females.
Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Exelixis Clinical Site #4	Atlanta	Georgia	United States	30322
2	Exelixis Clinical Site #3	Boston	Massachusetts	United States	02215
3	Exelixis Clinical Site #2	Dallas	Texas	United States	75230
4	Exelixis Clinical Site #5	Houston	Texas	United States	77030
5	Exelixis Clinical Site #1	San Antonio	Texas	United States	78229