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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06399757
• Other study ID #: AP10CP01
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: May 2024
• Est. completion date: May 2027

Study information

• Verified date: May 2024
• Source: Apollo Therapeutics Ltd
• Contact: Apollo Therapeutics
• Phone: 781-479-2267
• Email: AP10[@]apollotx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: May 2027
• Est. primary completion date: April 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 screening, 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Appendiceal Adenocarcinoma
• Cholangiocarcinoma
• Colorectal Cancer
• Endometrial Adenocarcinoma
• Gastric Adenocarcinoma
• Ovarian Cancer
• Pancreatic Adenocarcinoma
• Prostate Cancer
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Drug:
• APL-5125
APL-5125 is an oral drug (capsule) taken daily in 28-day cycles

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Apollo Therapeutics Ltd

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Emergent Adverse Events [Safety] (Phase 1)	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
Primary	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)
Primary	Estimate the maximum tolerated dose (MTD) of APL-5125 in participants with selected advanced solid tumors (Phase 1)		Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days)
Primary	Determine Recommended Phase 2 Dose (RP2D) levels of APL-5125 in participants with selected advanced solid tumors (Phase 1)		Approximately one year
Primary	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.)
Secondary	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.)
Secondary	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).
Secondary	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).
Secondary	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.)
Secondary	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)
Secondary	Further assess the PK of APL-5125 (Phase 2)	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).
Secondary	Further assess the PK of APL-5125 (Phase 2)	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).