AOH1996 for the Treatment of Refractory Solid Tumors

First in Human Phase 1 Study of AOH1996 in Patients With Refractory Solid Tumors

This phase I trial studies the side effects and best dose of AOH1996 in treating patients with solid tumors that do not respond to treatment (refractory). AOH1996 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; Ovarian Cancer; Non-Small Cell Lung Cancer; Osteosarcoma; Refractory Malignant Solid Neoplasm; Leiomyosarcomas; Synovial Sarcomas
• Intervention / Treatment: Drug: PCNA Inhibitor AOH1996

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of AOH1996.

II. To establish the recommended phase 2 dose of AOH1996.

III. To establish the recommended phase 2 dose of AOH1996 when given in conjunction with a TKI for NSCLC.

SECONDARY OBJECTIVES:

I. To determine the pharmacokinetics of AOH1996. II. To evaluate for preliminary efficacy of AOH1996. III. To evaluate response rate and disease control rate in solid tumors.

EXPLORATORY OBJECTIVE:

I. To determine pharmacodynamics parameters (alteration of gammaH2AX, downregulation of Myc) of AOH1996.

OUTLINE: This is a dose-escalation study.

Patients receive AOH1996 orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Vincent Chung, MD; Phone Number: 626-359-8111; Email: vchung@coh.org

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Not yet recruiting
      • Honor Health Research and Innovation Institute
      • Principal Investigator: Erkut Borazanci, MD
      • Contact: Patient Services; Phone Number: 800-826-4673; Email: ClinicaltrialAOH1996@coh.org
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Medical Center
      • Principal Investigator: Vincent Chung, MD
      • Contact: Patient Services; Phone Number: 800-826-4673; Email: ClinicaltrialAOH1996@coh.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Informed Consent and Willingness to Participate

• 1. Documented informed consent by the participant
• 2. Willingness to permit study team to obtain and use archival tissue, if already existing

Age Criteria, Performance Status and Life Expectancy

• 3. Age: ≥ 18 years
• 4. ECOG performance status ≤ 2
• 5. Life expectancy of > 3 months

Nature of Illness and Treatment History __6. Patients with solid tumors failing standard therapies or patients refusing standard treatments (exception: Part B NSCLC combination (EGFR TKI + AOH1996) cohort: patients with stable disease or better on EGFR TKI for at least 2 months)

Contraception

__7. Agreement by females and males of childbearing potential* to use an adequate method of birth control (hormonal contraception is inadequate) or abstain from heterosexual activity for the course of the study through 30 days after the last dose of study medication. See Appendix B for guidelines.

- Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only).

Laboratory Criteria (to be performed within 14 days prior to Day 1)

• 8. ANC ≥ 1,500/mm3
• 9. Platelets ≥ 100,000/mm3 :
• 10. Total serum bilirubin ≤ 1.5 x ULN
• 11. AST =< 1.5 x ULN or =< 3 x ULN with liver metastases
• 12. ALT =< 1.5 x ULN or =< 3 x ULN with liver metastases
• 13. Creatinine clearance of ≥ 60 mL/min per 24 hour urine or the Cockcroft-Gault
• 14. Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria

Concomitant Medications/Therapies __1. Dietary/herbal supplements

• 2. Other investigational products or chemotherapy. Exception: EGFR TKI in the NSCLC expansion cohort is allowed.
• 3. Warfarin
• 4. Current or planned use of agents contraindicated for use with strong CYP3A4 inducers
• 5. Strong inhibitors or inducers of CYP2C9
• 6. Strong inhibitors or inducers of CYP3A

Other Illnesses and Conditions

• 7. Issues with tolerating oral medication (e.g., inability to swallow pills, malabsorption issues, ongoing nausea or vomiting).
• 8. Women who are or are planning to become pregnant or breastfeed
• 9. Known allergy to any of the components within the study agents and/or their excipients.
• 10. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years.
• 11. Intercurrent or historic medical condition that increases subject risk in the opinion of the Investigator. Eligibility may be revisited for intercurrent medical conditions once resolution/recovery is deemed adequate by the investigator (e.g. recovery from major surgery, completion of treatment for severe infection).

Noncompliance

__12. Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics).

**Eligibility should be confirmed per institutional policies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (PCNA inhibitor AOH1996); Patients receive PCNA inhibitor AOH1996 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: PCNA Inhibitor AOH1996; Given PO; Other Names: AOH 1996; AOH-1996; AOH1996; Proliferating Cell Nuclear Antigen Inhibitor AOH1996

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs)	Toxicity and adverse events will be recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All toxicities/AEs will be recorded from the initiation of protocol therapy through the follow-up period.	Up to 30 days after last study drug is given
Dose limiting toxicities	Toxicities will be graded according to NCI CTCAE version 4.0.	Up to 28 days (cycle 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Will be assessed using Response Evaluation Criteria in Solid Tumors version 1. Response rate will be estimated in the overall population and 95% exact confidence intervals will be estimated.	Up to 2 years
Progression-free survival	Time to disease progression/ relapse or death as a result of any cause.	Assessed up to 2 years
Overall survival	Time to death as a result of any cause.	Assessed up to 2 years
Time to treatment failure	Time to treatment termination for any reason (progression, toxicity, death, patient preference).	Assessed up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of plasma gammaH2AX	Will use descriptive statistics and graphical displays to summarize levels of plasma gammaH2AX, evaluate changes between pre- and post-treatment measurements. A paired t-test will be used to determine if there is a statistically significant change.	Up to 2 years

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Vincent Chung, MD, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2022
• Primary Completion (Estimated): September 13, 2029
• Study Completion (Estimated): September 13, 2029

Study Registration Dates

• First Submitted: January 11, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma, Bronchogenic; Bronchial Neoplasms; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Ovarian Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Leiomyosarcoma; Sarcoma, Synovial; Osteosarcoma
• Other Study ID Numbers: 21310 (Other Identifier: City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2021-14102 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No