Trial Title:
A Phase I/IIa Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AZD0022 as Monotherapy and in Combination With Anti-cancer Agents in Adult Participants With Tumours Harbouring a KRASG12D Mutation
NCT ID:
NCT06599502
Condition:
Advanced Solid Tumours
Non-Small Cell Lung Cancer (NSCLC)
Pancreatic Ductal Adenocarcinoma (PDAC)
Colorectal Cancer (CRC)
Conditions: Official terms:
Adenocarcinoma
Cetuximab
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
This protocol has a modular design, with the potential for future Modules or treatment to
be added via protocol amendments. Participants will receive oral doses of AZD0022, either
as monotherapy or in combination with other anti-cancer agents
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AZD0022
Description:
AZD0022 is an oral KRASG12D inhibitor that blocks KRASG12D function in patients with this
type of mutation.
Arm group label:
Module 1 Part A. Dose Escalation
Arm group label:
Module 1 Part B. Dose Optimisation
Arm group label:
Module 1 Part B. Food Effect Cohort
Arm group label:
Module 1 Part C. Potential Efficacy Expansion
Arm group label:
Module 2 Part A. Dose Escalation
Arm group label:
Module 2 Part B. Dose Optimisation
Arm group label:
Module 2 Part C. Potential Efficacy Expansion
Intervention type:
Drug
Intervention name:
Cetuximab
Description:
Cetuximab (Erbitux®) is a recombinant chimeric human/mouse Immunoglobulin G monoclonal
antibody which binds to EGFR and competitively inhibits the binding of EGFR and other
ligands
Arm group label:
Module 2 Part A. Dose Escalation
Arm group label:
Module 2 Part B. Dose Optimisation
Arm group label:
Module 2 Part C. Potential Efficacy Expansion
Summary:
This is a first-in-human, modular, Phase I/IIa, open-label, multi-centre study to assess
the safety, tolerability, PK, and preliminary efficacy of AZD0022 monotherapy in
combination with other anti-cancer agents in participants with tumours harbouring a
KRASG12D mutation.
Detailed description:
This first time in human, open-label, multi-centre study will administer AZD0022 orally
to participants with tumours harbouring a KRASG12D mutation.
This study will have initially 2 modules.
- Module 1: AZD0022 monotherapy
- Module 2: AZD0022 in combination with other anti-cancer agents (Cetuximab)
Each Module has 3 parts. Dose Escalation (Part A), Dose Optimisation (Part B) and
Potential Efficacy Expansion (Part C).
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
For whole study:
1. Participant must be ≥ 18 years or the legal age of consent in the jurisdiction in
which the study is taking place at the time of signing the ICF.
2. Participants must have a histologically or cytologically confirmed metastatic or
locally advanced tumour. Further details on tumour types are specified in
Module-specific inclusion criteria.
3. Participants must have received and progressed on, are refractory or are intolerant
to standard therapy for the specific tumour type, or as per Module-specific
criteria. Participants with contraindications to, or who refuse SoC therapy may be
considered, provided that it is documented and the participant has been informed
about all available therapeutic options.
4. Documented KRASG12D mutation in tissue or liquid biopsy.
5. Provision of a FFPE tumour sample.
6. Participants must have at least one measurable target lesion per RECIST v1.1.
7. Adequate organ and marrow function as defined in study protocol.
Module 1 Key Inclusion Criteria
1. Type of tumours with a KRASG12D mutation:
1. For NSCLC: Patients must have NSCLC that is not amenable to curative treatment
and should have progressed on at least one prior line of SoC treatment for
metastatic NSCLC (including but not limited to platinum-based chemotherapy,
immunotherapy, targeted therapy or first line SoC combinations); prior
experimental treatments are allowed.
2. For CRC: Patients must have CRC that is not amenable to curative treatment and
should have progressed on at least 2 prior lines of SoC treatment for
metastatic CRC; prior experimental treatments are allowed.
3. For PDAC: Patients must have PDAC that is not amenable to curative treatment
and should have progressed at least one prior line of SoC treatment for
metastatic PDAC (including but not limited to FOLFIRINOX, gemcitabine plus
abraxane and gemcitabine monotherapy); prior experimental treatments are
allowed.
4. For patients enrolled in Part C (NSCLC and PDAC): at least one but no more than
2 lines of prior treatment in metastatic settings; prior experimental
treatments are allowed.
2. Progression or recurrence of the disease within 6 months of completing neo/adjuvant
treatment (ie, chemotherapy, immunotherapy, chemoradiotherapy, etc) will be
considered as a first line of treatment.
3. For Part B food-effect cohort, participants must be able to eat a standard high-fat
meal and must be able to fast for at least 10 hours.
Module 2 Inclusion Criteria
1. For Part A (M2A, dose escalation) participants must have pathologically documented
locally advanced or metastatic CRC with a KRASG12D mutation.
2. For Part B (M2B, dose optimisation) participants must have pathologically documented
locally advanced or metastatic, PDAC or CRC with a KRASG12D mutation.
3. For Part C (M2C, potential efficacy expansion) participants must have pathologically
documented locally advanced or metastatic CRC with a KRASG12D mutation.
4(a) For CRC: Patients must have CRC that is not amenable to curative treatment and
should have progressed on at least 2 prior lines of SoC treatment for metastatic CRC;
prior treatment are allowed.
(b) For PDAC: Patients must have PDAC that is not amenable to curative treatment and
should have progressed at least one prior line of SoC treatment for metastatic PDAC
(including but not limited to FOLFIRINOX, gemcitabine plus abraxane and gemcitabine
monotherapy); prior experimental treatment are allowed.
(c) For patients enrolled in Part C (M2C), at least 2 but no more than 3 lines of prior
treatment in metastatic setting; prior experimental treatment are allowed.
5. Progression or recurrence of the disease within 6 months of completing neo/adjuvant
treatment (ie, chemotherapy, immunotherapy, and chemoradiotherapy) will be
considered as a first line of treatment.
Exclusion Criteria:
For whole study:
1. Any significant laboratory finding or any severe and uncontrolled medical condition.
2. Any evidence of clinically significant current or prior ILD (eg, required IV
steroids or high supplemental oxygen) or where a new suspected ILD cannot be ruled
out by imaging at screening.
3. Spinal cord compression, leptomeningeal disease, or active brain metastases.
Asymptomatic brain metastases are allowed
4. History of allogenic organ transplantation.
5. Participants with any of the following cardiac criteria:
- Mean resting QTcF > 470 milliseconds on screening
- Any factors that increase the risk of QT prolongation
- Any clinically important abnormalities in rhythm, conduction or morphology of
resting ECG (eg, complete left bundle branch block, second- or third-degree
atrioventricular block), and clinically significant sinus node dysfunction not
treated with pacemaker.
- Bradycardia defined as a heart rate less than 60 beats per minute and/or
hypotension defined as a blood pressure reading lower than 90 mm Hg for the top
number (systolic) or 60 mm Hg for the bottom number (diastolic).
- Baseline LVEF below the institutional lower limit of normal or < 50%, whichever
is lower.
- Symptomatic heart failure (as defined by New York Heart Association class ≥ 2).
- Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris,
coronary intervention procedure with percutaneous coronary intervention, or
coronary artery bypass grafting within 6 months before C1D1.
6. Prior exposure to any direct small molecule KRAS inhibitor.
7. Herbal preparations/medications are not allowed during treatment with study drug.
8. Any concomitant medications that are known strong inhibitors or inducers of
CYP3A4/5, or sensitive CYP3A4/5 substrates or CYP3A4/5 substrates with a narrow
therapeutic range. This also applies to moderate inhibitors and moderate inducers of
CYP3A4/5 during Parts A and B of Modules 1 and 2.
9. Receipt of a cytotoxic or non-cytotoxic drug: 21 days or 5 half-lives, whichever is
shorter, before the first dose of study intervention. Biological therapy including
immune-oncology and monoclonal antibodies 28 days or 5 half-lives.
10. Less than or equal to 4 weeks for radiation therapy given with curative intent or ≤
2 weeks for limited field radiation for palliation prior to the first dose of study
treatment
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Research Site
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Kansas City
Zip:
64132
Country:
United States
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
New York
Zip:
10016
Country:
United States
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Melbourne
Zip:
3000
Country:
Australia
Status:
Recruiting
Facility:
Name:
Research Site
Address:
City:
Edegem
Zip:
2650
Country:
Belgium
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Leuven
Zip:
3000
Country:
Belgium
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Edmonton
Zip:
T6G 1Z2
Country:
Canada
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Toronto
Zip:
M5G 1X5
Country:
Canada
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Montreal
Zip:
H3A 1A1
Country:
Canada
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Milano
Zip:
20132
Country:
Italy
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Verona
Zip:
37134
Country:
Italy
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Amsterdam
Zip:
1066CX
Country:
Netherlands
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Gdańsk
Zip:
80-214
Country:
Poland
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Łódź
Zip:
93-513
Country:
Poland
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
L'Hospitalet de Llobregat
Zip:
08908
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Madrid
Zip:
28007
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Madrid
Zip:
28027
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Valencia
Zip:
46026
Country:
Spain
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Ankara
Zip:
06340
Country:
Turkey
Status:
Not yet recruiting
Facility:
Name:
Research Site
Address:
City:
Istanbul
Zip:
31755
Country:
Turkey
Status:
Not yet recruiting
Start date:
October 18, 2024
Completion date:
February 3, 2028
Lead sponsor:
Agency:
AstraZeneca
Agency class:
Industry
Source:
AstraZeneca
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06599502
