A Study of SY 5609, a Selective CDK7 Inhibitor, in Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

A Phase 1 Study of SY 5609, an Oral, Selective CDK7 Inhibitor, in Adult Patients With Select Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04247126
• Other study ID #: SY-5609-101
• Status: Completed
• Phase: Phase 1
• Start date: January 23, 2020
• Est. completion date: March 30, 2023

Study information

• Verified date: October 2023
• Source: Syros Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study consists of 2 parts. Part 1 is dose escalation and will first administer SY-5609 alone to participants with select advanced solid tumors and then in combination with fulvestrant to participants with HR positive, HER2-negative breast cancer. Part 2 is a dose expansion and will first administer SY-5609 in combination with gemcitabine and then SY-5609 in combination with gemcitabine and nab-paclitaxel in participants with pancreatic ductal adenocarcinoma (PDAC) .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: March 30, 2023
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years

2. Advanced Solid Tumors for which standard curative or palliative measures do not exist or are no longer effective (Group 1 only).

3. Postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. Participants must have failed prior treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor in combination with hormonal therapy in a previous line of therapy (Group 2 only).

4. Participants with histologically or cytologically confirmed PDAC with measurable metastatic lesion(s) (Groups 3 and 4 only).

5. Participants must have at least 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

6. All toxicities (except alopecia) from prior cancer treatments must have resolved to = Grade 1 before enrollment.

7. For women of childbearing potential (WCBP): negative serum ß human chorionic gonadotropin pregnancy test within 1 week before the first dose of SY 5609

8. Adequate organ and marrow function

9. Participants must be willing and able to comply with all aspects of the protocol

10. Participants must provide written informed consent before any study-specific screening procedures.

11. Albumin = 3.0 grams/deciliters (g/dL) (Groups 3 and 4 only).

Exclusion Criteria:

1. Chemotherapy or limited field radiotherapy within 2 weeks, wide field radiotherapy within 4 weeks, or nitrosoureas or mitomycin C within 6 weeks before entering the study

2. Major surgery within 2 weeks before starting the study treatment, or not recovered to baseline status from the effects of surgery received > 2 weeks prior

3. Received any other investigational agents within 4 weeks before enrollment, or < 5 half-lives since completion of previous investigational therapy, whichever is shorter

4. Received previous noncytotoxic, US Food and Drug Administration-approved anticancer agent within previous 2 weeks, or < 5 half-lives since completion of previous therapy, whichever is shorter

5. Known brain metastases or carcinomatous meningitis

6. Immunocompromised participants with increased risk of opportunistic infections

7. Participants with known active or chronic hepatitis B or active hepatitis C infection. Participants with a history of hepatitis C virus (HCV) infection who have completed curative therapy for HCV at least 12 weeks before Screening and have a documented undetectable viral load at Screening are eligible for enrollment.

8. Baseline QT interval corrected (QTc) with Fridericia's method > 480 milliseconds

• NOTE: criterion does not apply to participants with a right or left bundle branch block (QTc interval)

9. Female participants who are pregnant or breastfeeding

10. History of clinically significant cardiac disease or clinically relevant uncontrolled cardiac risk factors

11. Uncontrolled intercurrent illness.

12. Poorly controlled ascites requiring paracentesis within 1 month prior to entering the study. (Groups 3 and 4 only)

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Breast Cancer
• Pancreatic Cancer
• Small Cell Lung Carcinoma
• Small-cell Lung Cancer

Intervention

Drug:
• SY-5609
An oral CDK7 Inhibitor
• Fulvestrant
Estrogen receptor antagonist
• Gemcitabine
Nucleoside metabolic inhibitor
• Nab-paclitaxel
Taxane-type chemotherapy

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Duke University	Durham	North Carolina
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	START Midwest, LLC	Grand Rapids	Michigan
United States	The University of Iowa	Iowa City	Iowa
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of California Los Angeles	Los Angeles	California
United States	Sarah Cannon Research Institute - Tennessee Oncology	Nashville	Tennessee
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania
United States	South Texas Accelerated Research Theraputics (START), LLC	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Syros Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Groups 1 and 2: Dose-Limiting Toxicity of SY-5609		Up to 28 days after first administration
Primary	Groups 1 and 2: Number of Participants With Treatment Emergent Adverse Events		From Baseline up to 30 days after last dose of study drug (up to 1 year)
Primary	Groups 3 and 4 (Safety Lead-ins): Number of Participants With Dose-Limiting Toxicity		Up to 28 days after first administration
Primary	Groups 3 and 4 (Safety Lead-ins): Number of Participants With TEAEs		From Baseline up to 30 days after last dose of study drug (up to 1 year)
Primary	Groups 3 and 4 (Expansions): Progression Free Survival		Up to 1 year
Secondary	Groups 1 and 2: Area Under The Concentration Versus Time Curve of SY-6509		Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Secondary	Groups 1 and 2: Apparent Clearance of SY-5609		Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Secondary	Groups 1 and 2: Apparent Volume of Distribution of SY-5609		Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Secondary	Groups 1 and 2: Elimination Half-Life of SY-5609		Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Secondary	Groups 1 and 2: Maximum Plasma Concentration (Cmax) of SY-5609		Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Secondary	Groups 1 and 2: Time of Maximum Plasma Concentration (Tmax) of SY-5609		Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Secondary	Groups 1 and 2: Minimum or Trough Plasma Concentration (Cmin) of SY-5609		Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Secondary	Groups 1 and 2: Time of Minimum or Trough Plasma Concentration (Tmin) of SY-5609		Predose, 0.5, 1, 2, 4, 6, 8 hours postdose on Day 1 and 4 or 15 of Cycle 1; 24 hours predose on Day 2 and 5 of Cycle 1; 24 hours predose on Day 1 of Cycle 2, 3 and 4 (Each Cycle=28 days)
Secondary	Groups 3 and 4 (Safety Lead-ins): Progression Free Survival		Up to 1 year
Secondary	Groups 3 and 4 (Safety Lead-ins): Objective Response Rate (ORR)	ORR is defined as the proportion of participants who achieve complete response (CR) and partial remission (PR) (as determined by the investigator).	Up to 1 year
Secondary	Groups 3 and 4 (Safety Lead-ins): Complete Response/Remission (CR) Rate	CR rate is defined as proportion of participants who achieve CR (as determined by the investigator).	Up to 1 year
Secondary	Groups 3 and 4 (Safety Lead-ins): Disease Control Rate		Up to 1 year
Secondary	Groups 3 and 4 (Safety Lead-ins): Time to Response	Time to response is defined as the duration from the date of randomization to the date of the first documented evidence of response as determined by the investigator.	Up to 1 year
Secondary	Groups 3 and 4 (Safety Lead-ins): Duration of Response	Duration of response is defined as duration from the date of first documented evidence of response to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occurs first.	Up to 1 year
Secondary	Groups 3 and 4 (Expansions): Objective Response Rate	ORR is defined as the proportion of participants who achieve CR and partial remission (PR) (as determined by the investigator).	Up to 1 year
Secondary	Groups 3 and 4 (Expansions): Complete Response Rate	CR rate is defined as proportion of participants who achieve CR (as determined by the investigator).	Up to 1 year
Secondary	Groups 3 and 4 (Expansions): Disease Control Rate		Up to 1 year
Secondary	Groups 3 and 4 (Expansions): Time to Response	Time to response is defined as the duration from the date of randomization to the date of the first documented evidence of response as determined by the investigator.	Up to 1 year
Secondary	Groups 3 and 4 (Expansions): Duration of Response	Duration of response is defined as duration from the date of first documented evidence of response to the date of relapse of disease (as determined by the investigator), or death due to any cause, whichever occurs first.	Up to 1 year