Phase I Study of ZN-c3 and Bevacizumab ± Pembrolizumab in Metastatic CCNE1 Amplified and TP53 Mutant Solid Tumors

NCT05431582 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 2021-0175NCI-2022-05251
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary Objectives are to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of ZN-c3 and ZN-c3 and bevacizumab or ZN-c3 and bevacizumab plus pembrolizumab in metastatic CCNE1 amplified and TP53 mutant solid tumors as well to evaluate antitumor activity of ZN-c3 and bevacizumab or ZN-c3 and bevacizumab plus pembrolizumab in metastatic CCNE1 amplified and TP53 mutant solid tumors.

Conditions

Tumors; Ovarian Cancer; Breast Cancer; Lung Cancer; Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• To establish the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of ZN-c3 .

  through study completion, an average of 1 year

• To establish the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) ZN-c3 and bevacizumab.

  through study completion, an average of 1 year

Study Arms (2)

Regimen A

EXPERIMENTAL

ZN-c3 in combination with bevacizumab

Drug: ZN-c3; Drug: Bevacizumab

Regimen B

EXPERIMENTAL

ZN-c3 in combination with bevacizumab and pembrolizumab

Drug: ZN-c3; Drug: Bevacizumab; Drug: Pembrolizumab

Interventions

ZN-c3 DRUG

Given by PO 1 time a day with a glass (about 8 ounces) of water

Regimen A; Regimen B

Bevacizumab DRUG

Given by vein over about 30-60 minutes on Day 1 of each cycle

Also known as: Avastin™, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Regimen A; Regimen B

Pembrolizumab DRUG

Given by vein over 30-60 minutes on Day 1 of each cycle.

Also known as: KEYTRUDA®

Regimen B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed metastatic solid tumors harboring CCNE1 amplification and TP53 mutation pre-identified in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, either refractory to standard therapy or for which no effective standard therapy that increases survival for at least 3 months is available, or they declined standard of care therapy.
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Male or female aged ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Adequate organ functions as defined below:
• Absolute neutrophil count (ANC) ≥ 1,500 /μL. Hemoglobin (Hb) ≥ 8 g/dL. Platelets ≥ 100,000 /μL. Total bilirubin ≤ 1.5 x upper limit of normal (ULN); or total bilirubin \< 3.0 x ULN with direct bilirubin ≤ ULN in patients with well documented Gilbert's Syndrome.
• ALT ≤ 3 ULN or ≤ 5 ULN if liver metastases persist. Serum albumin ≥ 3 g/dL. Urinalysis ≤ 1 proteinuria, or urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol), or 24-h urine protein ≤ 1 g.
• PT/INR or partial thromboplastin time (PTT) test \< 1.3 the laboratory ULN if not on therapeutic anticoagulation.
• Calculated creatinine clearance (CrCl) ≥ 60 mL/min by the Cockcroft-Gault method\* or 24-hour urine collection.
• \* CrCl = (140-age) x (weight/kg) x Fa / (72 x serum creatinine mg/dL). a where F= 0.85 for females and F=1 for male
• Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to initiation of therapy (C1D1), and must agree to use effective birth control during the study prior to the first dose and for at least 6 months after the last dose (or longer based on local requirements). Female patients are not considered to be of child-bearing potential if they are post-menopausal (no menses for 12 months without an alternative medical cause) or permanently sterile (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). Male patients must agree to abstain or use barrier contraception (i.e. condoms), and avoid sperm donation for the duration of the study and for 6 months after treatment stops.
• Ability to read and fully understand the requirements of the trial, willingness to comply with all trial visits and assessments, and willingness and ability to sign an institutional review board (IRB)-approved written informed consent document (ICD). Patients with Impaired Decision Making Capacity (IDMC) must have a close caregiver or Legally Authorized Representative (LAR).
• Any prior palliative radiation must have been completed at least 14 days prior to the start of study drugs, and patients must have recovered from any acute adverse effects prior to the start of study treatment (Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks).
• Fridericia's corrected QT interval (QTcF =QT/∛(60/HR) ) ≤ 460 milliseconds (ms) for males and ≤ 480 ms for females on ECG conducted at rest during Screening.
• Note: Patients with an atrioventricular pacemaker or other condition (for example, right bundle branch block) that renders the QT measurement invalid are an exception and this criterion does not apply.

You may not qualify if:

• Any treatment specifically for systemic tumor control given within 3 weeks before the initiation of therapy; within 2 weeks if cytotoxic agents were given weekly, within 6 weeks for nitrosoureas or mitomycin C; within 5 half-lives for targeted agents with half-lives and pharmacodynamic effects lasting \< 5 days; or failure to recover from toxic effects of any previous therapy. A drug that has not received regulatory approval for any indication within 14 or 21 days of treatment for a non-myelosuppressive or myelosuppressive agent, respectively: patients must recover for previous cancer therapy, and are ready to proceed with further cancer therapy.
• Uncontrolled intercurrent illness including but not limited to:
• ongoing or active infection requiring intravenous antibiotics
• symptomatic congestive heart failure (New York Heart Association Class III or IV)
• history of myocardial infarction, unstable angina, stroke or transient ischemic attack within 6 months before study enrollment
• lesions invading or encasing any major blood vessels and cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation
• Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment
• history or current evidence of uncontrolled ventricular arrhythmia
• congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death
• clinically significant bleeding or active gastric or duodenal ulcer
• chronic diarrhea diseases considered to be clinically significant
• Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment, or any gastrointestinal disorders associated with a high risk of perforation or fistula formation.
• other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation, or may interfere with the interpretation of study results, and in the judgment of the Investigator would make the patient inappropriate for entry into this study.
• Unresolved clinically significant Grade 1 or higher toxicity from prior therapy.
• History of allergic reactions to the study drugs, or any component of the products.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Zentalis Pharmaceuticals: collaborator

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Lung Neoplasms; Pancreatic Neoplasms

Interventions

Bevacizumab; pembrolizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Siqing Fu, MD, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2022
• First Posted: June 24, 2022
• Study Start: December 14, 2022
• Primary Completion: December 14, 2022
• Study Completion: December 14, 2022
• Last Updated: June 15, 2023

Record last verified: 2023-02