A Study to Investigate APL-5125 in Adults With Advanced Solid Tumors

A Phase 1/2 Study to Assess the Safety and Antitumor Activity of APL-5125 in Adults With Selected Advanced Solid Tumors

This is an open-label, Phase 1/2 study to determine the safety, tolerability, and efficacy of APL-5125 for the treatment of selected locally advanced or metastatic solid tumors with particular focus on Colorectal carcinoma (CRC).

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Pancreatic Adenocarcinoma; Ovarian Cancer; Prostate Cancer; Gastric Adenocarcinoma; Cholangiocarcinoma; Triple Negative Breast Cancer; Endometrial Adenocarcinoma; Appendiceal Adenocarcinoma
• Intervention / Treatment: Drug: APL-5125

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Apollo Therapeutics; Phone Number: 781-479-2267; Email: AP10@apollotx.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Active, not recruiting
      • City of Hope
    • Irvine, California, United States, 92618
      • Active, not recruiting
      • City of Hope Orange County Lennar Foundation Cancer Center
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists & Research Institute
      • Contact: Carly Taylor; Email: ctaylor@flcancer.com
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: University of Michigan Cancer AnswerLine; Phone Number: 800-865-1125; Email: CancerAnswerLine@med.umich.edu
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Cancer Institute
      • Contact: Sabina Wlazlo Cascalheiro; Phone Number: 919-613-4812; Email: sabina.wlazlo@duke.edu
    • Huntersville, North Carolina, United States, 28078
      • Recruiting
      • Carolina BioOncology Institute
      • Contact: Hannah Wall; Phone Number: 980-441-1148; Email: hwall@carolinabiooncology.org
      • Contact: Phone Number: 704-947-6599
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75251
      • Recruiting
      • Mary Crowley Cancer Research
      • Contact: Department Contact; Email: referral@marycrowley.org
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology- San Antonio
      • Contact: Jordan Georg; Phone Number: 210-580-9521; Email: jgeorg@nextoncology.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years or older
• Phase 1: Histologically confirmed locally advanced, inoperable, or metastatic tumor; Colorectal carcinoma, Cholangiocarcinoma, Appendiceal adenocarcinoma.
• For Phase 1 sub-studies: Colorectal carcinoma, Cholangiocarcinoma, Appendiceal adenocarcinoma, Pancreatic Adenocarcinoma, Gastric Adenocarcinoma, Endometrial Adenocarcinoma, Triple Negative Breast Cancer, Ovarian Cancer, Prostate Cancer
• Phase 2: Colorectal carcinoma

• No available standard of care therapy or participant is ineligible for standard of care therapy, except in CRC tumor type in which participant must have previously received all the following therapeutic agents:

  • fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy
  • an anti-VEGF therapy
  • if wt-RAS (wt-KRAS and wt-NRAS), an anti-EGFR therapy
• Eastern Cooperative Oncology Group (ECOG) ≤1
• Body Weight ≥40 kg.
• Female participants of childbearing potential must have negative serum pregnancy test at screening; must not plan to become pregnant or have ova harvested or breastfeed while on study; must be willing to use specific contraception or avoid intercourse
• Male participants must be willing to use specific contraception and not plan to impregnate a female partner or donate sperm while on study
• Participant must be willing and able to provide written informed consent and to comply with the requirements of the trial

Exclusion Criteria:

• Certain medical conditions such as: active brain metastases, carcinomatous meningitis, unstable angina pectoris, myocardial infarction or clinically significant ventricular arrhythmias, symptomatic congestive heart failure, uncontrolled active infection, history of significant hemorrhage within 4 weeks of the first dose date, intestinal disease or major gastric surgery, arterial thrombosis within 6 months of screening
• Certain prior therapies such as: anti-cancer treatment within 2 weeks of Cycle 1 Day 1, prior radiotherapy within 14 days before screening, active anti-coagulation therapy, over the counter or prescription medications within 14 days or 5 half-lives prior to cycle 1 day 1, herbal medicines and supplements within 14 days
• Major surgery within 1 month of screening
• Hemoglobin < 9.0 g/dL
• Absolute neutrophil count < 1.5 x 10^9/L
• Platelet count < 100 x 10^9/L

• Hepatic function:

  1. Aspartate aminotransferase and/or alanine aminotransferase (ALT) >3 × upper limit of normal (ULN) (>5 x ULN for subjects with liver metastases)
  2. Total bilirubin >1.5 × ULN (except participants with Gilbert's syndrome).
  3. Albumin < 3 g/dL
• Calculated or measured creatinine clearance of <60 mL/minute calculated using the formula of Cockcroft and Gault ([140 - Age] × Mass [kg] / [72 × serum creatinine mg/dL]). Multiply result by 0.85 if female.
• Fridericia's corrected QT interval (QTcF) >470 msec or a family history of Long QT Syndrome.
• Cardiac function: Echocardiogram (or MUGA) showing Left Ventricular Ejection Fraction (LVEF) <45% at rest
• Infectious diseases: positive for HIV (unless controlled with active retroviral therapy), hepatitis B and hepatitis C

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Dose Escalation; Dose escalation with increasing dose levels of APL-5125 to identify Recommended Phase 2 Dose. Possibility to expand into select populations	Drug: APL-5125; APL-5125 is an oral drug (capsule) taken daily in 28-day cycles
Experimental: Phase 2: Dose Expansion/Optimization; At least 2 dose levels of APL-5125 in a selected population	Drug: APL-5125; APL-5125 is an oral drug (capsule) taken daily in 28-day cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicities [Tolerability] (Phase 1)	Evaluation of tolerability parameters including dose limiting toxicities as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs and electrocardiogram results	Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)
Determine Recommended Phase 2 Dose (RP2D) levels of APL-5125 in participants with selected advanced solid tumors (Phase 1)		Approximately one year
Assess the anti-tumor activity of APL-5125 in patients with Colorectal carcinoma (Phase 2)	Response is assessed per RECIST version 1.1 criteria	Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)
Incidence of Treatment Emergent Adverse Events [Safety]	Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, electrocardiogram results.	Through study completion, approximately one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the preliminary anti-tumor activity of APL-5125 in colorectal carcinoma patients (Phase 1)	Response is assessed per RECIST version 1.1 criteria	Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)
Assess the pharmacokinetics (PK) of APL-5125 (Phase 1)	Evaluate PK parameters: oral clearance	On days 1, 2, 4, 8, 15 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).
Assess the pharmacokinetics (PK) of APL-5125 (Phase 1)	Evaluate PK parameters: volume of distribution	On days 1, 2 ,4, 8, 15 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).
Further assess the anti-tumor activity of APL-5125 (Phase 2)	Response is assessed per RECIST version 1.1 criteria	Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.)
Incidence of treatment emergent adverse events [Further Safety] (Phase 2)	Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, electrocardiogram results	Through study completion (approximately 2 years)
Further assess the PK of APL-5125 (Phase 2)	Evaluate PK parameters: oral clearance	On days 1 and 8 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).
Further assess the PK of APL-5125 (Phase 2)	Evaluate PK parameters: volume of distribution	On days 1 and 8 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days).
Evaluate biomarker(s) in the tumor	Assessment of biomarker(s) in pre- and post-treatment tumor tissue	Through study completion, approximately one year

Collaborators and Investigators

• Sponsor: Apollo Therapeutics Ltd
• Investigators: Study Chair: Sanjay Aggarwal, MD, Apollo Therapeutics Ltd

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: May 1, 2024
• First Submitted That Met QC Criteria: May 1, 2024
• First Posted (Actual): May 6, 2024

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Colonic Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Carcinoma; Neoplasms, Cystic, Mucinous, and Serous; Breast Neoplasms; Skin and Connective Tissue Diseases; Prostatic Neoplasms; Colorectal Neoplasms; Ovarian Neoplasms; Cholangiocarcinoma; Triple Negative Breast Neoplasms; Adenocarcinoma, Mucinous
• Other Study ID Numbers: AP10CP01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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