Appendiceal Adenocarcinoma, Cholangiocarcinoma, Colorectal Cancer, Endometrial Adenocarcinoma, Gastric Adenocarcinoma, Ovarian Cancer, Pancreatic Adenocarcinoma, Prostate Cancer, Triple Negative Breast Cancer
Conditions
Brief 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).
Interventions
DRUGAPL-5125
APL-5125 is an oral drug (capsule) taken daily in 28-day cycles
Sponsors
Apollo Therapeutics Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events [Safety] | Through study completion, approximately one year | Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, electrocardiogram results. |
| Incidence of dose limiting toxicities [Tolerability] (Phase 1) | Cycle 1 Day 1 to Cycle 2 Day 1 (a cycle is 28 days) | Evaluation of tolerability parameters including dose limiting toxicities as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs and electrocardiogram results |
| 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 every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.) | Response is assessed per RECIST version 1.1 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the preliminary anti-tumor activity of APL-5125 in colorectal carcinoma patients (Phase 1) | Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.) | Response is assessed per RECIST version 1.1 criteria |
| Assess the pharmacokinetics (PK) of APL-5125 (Phase 1) | 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). | Evaluate PK parameters: oral clearance |
| Evaluate biomarker(s) in the tumor | Through study completion, approximately one year | Assessment of biomarker(s) in pre- and post-treatment tumor tissue |
| Further assess the anti-tumor activity of APL-5125 (Phase 2) | Response is assessed every 8 weeks; after one year of treatment, response is assessed every 12 weeks. (Assessed for up to 2 years.) | Response is assessed per RECIST version 1.1 criteria |
| Incidence of treatment emergent adverse events [Further Safety] (Phase 2) | Through study completion (approximately 2 years) | Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, electrocardiogram results |
| Further assess the PK of APL-5125 (Phase 2) | On days 1 and 8 of cycle 1, and on day 1 of cycle 2 and cycle 3 (a cycle is 28 days). | Evaluate PK parameters: oral clearance |
Countries
United States
Contacts
STUDY_CHAIRSanjay Aggarwal, MD
Apollo Therapeutics Ltd
Outcome results
None listed