ACCENT: AMP945 in Combination with Nab-paclitaxel and Gemcitabine for Treatment of Pancreatic Cancer

NCT05355298 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AMP945-PC-201
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 13

Brief Summary

This is a multicentre, open label, two-part study to determine whether the focal adhesion kinase (FAK) inhibitor AMP945, when given prior to dosing with gemcitabine and nab-paclitaxel, improves response to therapy in first-line patients with unresectable or metastatic pancreatic cancer. Part A is a phase 1b dose-escalation design that will enrol at least 3 participants in each of 4 dose-level cohorts, to determine the RP2D of AMP945 to be explored in Part B. Part B will determine the efficacy of the AMP945 regimen at the RP2D, and will be run as a Simon Two-stage design; Stage 1 will enrol 26 participants. If ≤5 of the 26 participants show an objective response, then recruitment will be paused and a detailed analysis of futility will be performed. If the study is deemed futile, recruitment will cease. If the study is determined to be not futile or \>5 of the 26 participants show an objective response, recruitment will continue, and an additional 24 participants will be enrolled in Stage 2.

Conditions

Pancreatic Cancer; PDAC; Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) from Baseline to End of Study

  TEAEs during study treatment and follow up periods

  From first dose of study drug to end of study, an expected average of 6 months

• Part A: Determination of RP2D

  The RP2D of AMP945 will be determined based on either the maximum tolerated dose or maximum pharmacodynamic effect, which ever is reached first

  After Cycle 1 (28 days) for each Part A cohort

• Part B: efficacy of AMP945

  Overall response rate based on RECIST 1.1

  Imaging every 56 days per participant, with an expected average duration of 6 months

Secondary Outcomes (4)

• Part A: efficacy of AMP945

  Imaging every 56 days per participant, with an expected average duration of 6 months

• AMP945 levels in plasma

  Days -8, -7, 1, 3, 4, 8 and 10

• AMP945 levels in plasma

  Days -8, -7, 1, 3, 4, 8 and 10

• AMP945 levels in plasma

  Days -8, -7, 1, 3, 4, 8 and 10

Other Outcomes (8)

• Overall response

  Imaging every 56 days per participant, with an expected average duration of 6 months

• Duration of response (DOR)

  Imaging every 56 days per participant, with an expected average duration of 6 months

• Overall survival (OS)

  Imaging every 56 days per participant, with an expected average duration of 6 months

Study Arms (1)

AMP945

EXPERIMENTAL

Part A: AMP945 administered in dose escalating cohorts Part B: AMP945 recommended phase 2 dose

Drug: AMP945 ascending doses; Drug: AMP945 RP2D

Interventions

AMP945 ascending doses DRUG

Part A is a phase 1b dose-escalation design that will enrol at least 3 participants in each of 4 dose-level cohorts, to determine the RP2D of AMP945 to be explored in Part B. Dose escalation decisions will be made using a standard 3+3 dose-escalation phase 1 oncology study design.

AMP945

AMP945 RP2D DRUG

Part B will determine the efficacy of the AMP945 priming regimen at the recommended phase 2 dose (RP2D) determined in Part A.

AMP945

Eligibility Criteria

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

You may qualify if:

• Provide written informed consent prior to any study procedures and agree to adhere to all protocol requirements.
• Aged at least 18 years at the time of consent.
• Confirmed histological or cytological diagnosis of advanced pancreatic adenocarcinoma that is:
• Part A: metastatic or not surgically resectable.
• Part B: metastatic, with initial diagnosis of metastatic disease ≤6 weeks prior to Baseline.
• Has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
• Eligible for treatment with nab-paclitaxel and gemcitabine as standard of care therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1, sustained on two separate assessments: the first at least 2 weeks prior to the 1st dose of AMP945 and the 2nd within 72 hours prior to the 1st dose of AMP945. Participants not maintaining an ECOG Performance Score of 0-1 at the second assessment will be excluded from participation.
• Has a life expectancy of \>3 months.
• Adequate organ function, as defined by the laboratory results below (samples must be obtained ≤14 days prior to study drug administration):
• a) Haematology:
• (i) Absolute neutrophil count (ANC) ≥1.5 × 109/L;
• (ii) Platelet count ≥100,000/mm3 (100 × 109/L);
• (iii) Haemoglobin (Hgb) ≥9 g/dL.
• b) Serum chemistry:

You may not qualify if:

• Pregnant or breast-feeding, or plans to become pregnant during the study.
• Has received any investigational medicinal product (IMP) within 30 days or 5 half-lives (whichever is longer) prior to Day -8.
• Known brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no oedema, no steroids and stable in 2 scans at least 4 weeks apart).
• Gastrointestinal condition that could interfere with the swallowing or absorption of study medication.
• Part A: Has received prior systemic treatments for pancreatic cancer, except those given in the adjuvant setting, and with recurrence more than 6 months after completion of curative/adjuvant treatment.
• Part B: Has received no previous radiotherapy, surgery, chemotherapy, or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present. Participants having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study.
• History of malignancy other than in situ cancer or basal or squamous cell skin cancer in the last 5 years.
• Major surgery, other than diagnostic surgery (i.e., surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day -8.
• Known human immunodeficiency virus (HIV) and/or history of Hepatitis B or C infections or known to be positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C Antibody.
• Known history of myocardial infarction, coronary stenting, stroke, or cerebrovascular accident within 6 months prior to the first dose of study drug.
• Focal palliative radiotherapy (e.g., to a bony metastasis) within the 14 days prior to Run-in, or more extensive radiotherapy within 28 days prior to Run-in.
• History of chronic leukemias (e.g., chronic lymphocytic leukemia).
• History of interstitial lung disease, history of slowly progressive dyspnoea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
• History of connective tissue disorders (e.g., lupus, scleroderma, arteritis nodosa).
• Clinical signs of active infection and/or a temperature of \> 38.0°C at the time of Screening or Baseline. Study entry may be deferred at the discretion of the Principal Investigator (PI).

Sponsors & Collaborators

• Amplia Therapeutics Limited: lead

Study Sites (13)

GenesisCare

St Leonards, New South Wales, 2065, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Gallipolli Medical Research Foundation

Greenslopes, Queensland, 4120, Australia

Location

Epworth Healthcare

Box Hill, Victoria, 3128, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Epworth Healthcare

Richmond, Victoria, 3121, Australia

Location

Western Health

St Albans, Victoria, 3021, Australia

Location

National Cancer Centre

Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Severence Hospital

Seoul, 03722, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Samsung Medical Centre

Seoul, 6351, South Korea

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Design

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

Model Details: Single arm study but 2 parts; * Part A is dose escalation * Part B is open label single dose level

Study Record Dates

• First Submitted: April 7, 2022
• First Posted: May 2, 2022
• Study Start: May 31, 2022
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: February 5, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (5); AU (8)