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

• ClinicalTrials.gov Identifier: NCT04726332
• Recruitment Status: Recruiting
• First Posted: January 27, 2021
• Last Update Posted: April 26, 2022
• Sponsor: Exelixis
• Information provided by (Responsible Party): Exelixis

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 (Clinical Trial)
• Estimated Enrollment: 298 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: single-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: February 10, 2021
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: October 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 :

1. Dose-Escalation Stage: MTD/recommended dose for XL102 [ Time Frame: 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
2. Cohort-Expansion Stage: Objective Response Rate (ORR) [ Time Frame: 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 :

1. Safety of XL102 as evaluated by Incidence and Severity of Adverse Events (AEs) [ Time Frame: 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.
2. Tolerability of XL102 as evaluated by Study Treatment Exposure, Dose Intensity and Modifications, and Study Treatment Discontinuation due to AE [ Time Frame: 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.
3. Dose-Escalation Stage: Drug-Drug Interactions [ Time Frame: Approximately 18 months ]
   To assess drug-drug interactions between XL102 and combination agents
4. Dose-Escalation Stage: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: Approximately 18 months ]
   To evaluate the Tmax of XL102 alone and in combination therapy
5. Dose-Escalation Stage: Maximum Plasma Concentration (Cmax) [ Time Frame: Approximately 18 months ]
   To evaluate the Cmax of XL102 alone and in combination therapy
6. Dose-Escalation Stage: Area Under the Plasma Concentration-Time Curve Over the Last 24-hour Dosing Interval (AUC 0-24) [ Time Frame: Approximately 18 months ]
   To evaluate the AUC 0-24 of XL102 alone and in combination therapy
7. Dose-Escalation Stage: Terminal Half-Life [ Time Frame: Approximately 18 months ]
   To evaluate the terminal half-life of XL102 alone and in combination therapy
8. Dose-Escalation Stage: Apparent Clearance (CL/F) [ Time Frame: Approximately 18 months ]
   To evaluate the CL/F of XL102 alone and in combination therapy

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts

Contact: Exelixis Clinical Trials; 1-888-EXELIXIS (888-393-5494); druginfo@exelixis.com

Contact: Backup or International; 650-837-7400

Locations

United States, Georgia

Exelixis Clinical Site #4; Recruiting

Atlanta, Georgia, United States, 30322

United States, Massachusetts

Exelixis Clinical Site #3; Recruiting

Boston, Massachusetts, United States, 02215

United States, Texas

Exelixis Clinical Site #2; Recruiting

Dallas, Texas, United States, 75230

Exelixis Clinical Site #5; Recruiting

Houston, Texas, United States, 77030

Exelixis Clinical Site #1; Recruiting

San Antonio, Texas, United States, 78229

Sponsors and Collaborators

Exelixis

More Information

• Responsible Party: Exelixis
• ClinicalTrials.gov Identifier: NCT04726332
• Other Study ID Numbers: XL102-101
• First Posted: January 27, 2021
• Last Update Posted: April 26, 2022
• Last Verified: April 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Exelixis:

cdk7 inhibitor

Additional relevant MeSH terms:

Triple Negative Breast Neoplasms; Breast Neoplasms; Carcinoma, Ovarian Epithelial; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases; Urogenital Diseases; Ovarian Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Neoplasms, Female; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Prednisone; Fulvestrant; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs