Advanced Solid TumoursPhase 1ALAFOSS-01NCT06599502
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
A Phase 1 study testing AZD0022 and Cetuximab in people with Advanced Solid Tumours and Non-Small Cell Lung Cancer (NSCLC), run by AstraZeneca at 6 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumours, Non-Small Cell Lung Cancer (NSCLC), Pancreatic Ductal Adenocarcinoma (PDAC)
- What is being tested?
- AZD0022 and Cetuximab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 18 Oct 2024to 29 Jan 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For whole study:
- 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.
- 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.
- 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.
- Documented KRASG12D mutation in tissue or liquid biopsy.
- Provision of a FFPE tumour sample.
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- Participants must have at least one measurable target lesion per RECIST v1.1.
- Adequate organ and marrow function as defined in study protocol.
- Module 1 Key Inclusion Criteria
- Type of tumours with a KRASG12D mutation:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
- For Part A (M2A, dose escalation) participants must have pathologically documented locally advanced or metastatic CRC with a KRASG12D mutation.
- For Part B (M2B, dose optimisation) participants must have pathologically documented locally advanced or metastatic, PDAC or CRC with a KRASG12D mutation.
- 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.
- 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.
- 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.
Who cannot join
- For whole study:
- Any significant laboratory finding or any severe and uncontrolled medical condition.
- 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.
- Spinal cord compression, leptomeningeal disease, or active brain metastases. Asymptomatic brain metastases are allowed
- History of allogenic organ transplantation.
- Participants with any of the following cardiac criteria:
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- 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.
- Prior exposure to any direct small molecule KRAS inhibitor.
- Herbal preparations/medications are not allowed during treatment with study drug.
- 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.
- 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.
- 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
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
United States3 sites
Research Site
Duarte, California, 91010
Research Site
Fairfax, Virginia, 22031
Research Site
New York, New York, 10016
About this study
Official title: A Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD0022 Monotherapy and in Combination With Anti-cancer Agents in Participants With Tumours Harbouring a KRASG12D Mutation (ALAFOSS-01)
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.
Read the 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).
- Conditions
- Advanced Solid Tumours, Non-Small Cell Lung Cancer (NSCLC), Pancreatic Ductal Adenocarcinoma (PDAC), Colorectal Cancer (CRC)
- Being tested
- AZD0022, Cetuximab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD0022Drug
AZD0022 is an oral KRASG12D inhibitor that blocks KRASG12D function in patients with this type of mutation.
CetuximabDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Module 1 Part A. Dose Escalation | Experimental | AZD0022 monotherapy Receives: Drug: AZD0022 |
| Module 1 Part B. Dose Optimisation | Experimental | AZD0022 monotherapy Receives: Drug: AZD0022 |
| Module 1 Part C. Potential Efficacy Expansion | Experimental | AZD0022 monotherapy Receives: Drug: AZD0022 |
| Module 1 Part B. Food Effect Cohort | Experimental | AZD0022 monotherapy Receives: Drug: AZD0022 |
| Module 2 Part A. Dose Escalation | Experimental | AZD0022 in combination with Cetuximab Receives: Drug: AZD0022; Drug: Cetuximab |
| Module 2 Part B. Dose Optimisation | Experimental | AZD0022 in combination with Cetuximab Receives: Drug: AZD0022; Drug: Cetuximab |
| Module 2 Part C. Potential Efficacy Expansion | Experimental | AZD0022 in combination with Cetuximab Receives: Drug: AZD0022; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of participants with Dose-Limiting Toxicity (DLT), Adverse events (AEs) and Serious Adverse Events (SAEs).
Determine if treatment with AZD0022 as a monotherapy and in combination with other anti-cancer agents is safe and tolerable through the assessment of DLTs, AEs, SAEs, and change from baseline in laboratory parameters, vital signs, and ECGs.
Part A (Dose Escalation) and Part B (Dose Optimisation). DLTs only applicable for Part A.
Measured: From time of informed consent, through study completion to 30 days post last dose; an average of 2 years
Number of patients who discontinue AZD0022 due to toxicity
To investigate the safety and tolerability of AZD0022 as a monotherapy and in combination with other anti-cancer agents in participants with advanced tumours harbouring a KRASG12D mutation
Part A (Dose Escalation) and Part B (Dose Optimisation)
Measured: From time of informed consent to 30 days post last dose
ORR (Objective Response Rate)
Evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Part C (Potential Efficacy Expansion)
Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR)
Measured: Time from first dose of AZD002 through study completion; approximate duration of 2 years
Secondary outcomes (23)
CR rate (Complete Response)
To assess the preliminary anti-tumour activity of AZD0022 as a monotherapy and in combination with other anti-cancer agents
Radiological response evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Part A (Dose Escalation), Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion)
Percentage of participants with a confirmed Complete Response (CR)
Measured: From first dose (non-randomised study parts) or from randomisation (randomised) through study completion; approximate duration of 2 years
DoR (Duration of Response)
To assess the preliminary anti-tumour activity of AZD0022 as a monotherapy and in combination with other anti-cancer agents
Radiological response evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Part A (Dose Escalation), Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion).
Time from the date of first documented evidence of CR or PR until date of first documented disease progression or death.
Measured: From the date of first response until date of disease progression (RECIST 1.1) or death in the absence of disease progression; approximate duration of 2 years.
DCR (Disease Control Rate)
To assess the preliminary anti-tumour activity of AZD0022 as a monotherapy and in combination with other anti-cancer agents
Radiological response evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Part A (Dose Escalation), Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion).
Percentage of participants who have a confirmed CR, PR, or Stable Disease (SD) for at least 11 weeks after start of treatment.
Measured: From first dose (non-randomised study parts) or from randomisation (randomised) until progression. For each patient, this is expected to be at 12 weeks
DRR (Durable Response Rate)
To assess the preliminary anti-tumour activity of AZD0022 as a monotherapy and in combination with other anti-cancer agents
Radiological response evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Part A (Dose Escalation), Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion).
Percentage of participants who have a confirmed response (CR/PR) with a duration of at least 3 months.
Measured: From first documented response up until progression, or the last evaluable assessment in the absence of progression; approximate duration of 2 years.
TTR (Time to Response)
To assess the preliminary anti-tumour activity of AZD0022 as a monotherapy and in combination with other anti-cancer agents
Radiological response evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Part A (Dose Escalation), Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion)
Time from first dose/randomisation date until date of first documented evidence of CR or PR per RECIST v1.1
Measured: From first dose (non-randomised study parts) or from randomisation (randomised study parts) until the date of documented objective response; approximate duration of 2 years.
PFS (Progression Free Survival)
To assess the preliminary anti-tumour activity of AZD0022 as a monotherapy and in combination with other anti-cancer agents
Radiological response evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Part A (Dose Escalation), Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion).
Time from first dose/randomisation date until date of first documented disease progression or death.
Measured: 'From first dose (non-randomised study parts) or from randomisation (randomised study parts) to progressive disease or death in the absence of disease progression; approximate duration of 2 years
Change in tumour size
To assess the preliminary anti-tumour activity of AZD0022 as a monotherapy and in combination with other anti-cancer agents
Radiological response evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Part A (Dose Escalation), Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion)
Percentage change in tumor size from baseline per RECIST v1.1
Measured: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised), at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
OS (Overall Survival)
To assess the preliminary anti-tumour activity of AZD0022 as a monotherapy and in combination with other anti-cancer agents
Part A (Dose Escalation), Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion).
Time from first dose/randomisation date until death due to any case.
Measured: From first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts) to death; approximate duration of 2 years.
Complete Molecular Response (cMR).
To assess the molecular response rate via ctDNA on treatment with AZD0022 as a monotherapy and in combination with other anti-cancer agents
Part A (Dose Escalation), Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion).
Measured: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts), at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
Pharmacokinetics of AZD0022: Maximum plasma concentration of the study drug (Cmax)
Maximum observed plasma concentration of the study drug
Part A (Dose Escalation) and Part B (Dose Optimisation)
Measured: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts), at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
Pharmacokinetics of AZD0022: Time to maximum plasma concentration of the study drug (T-max)
Time to maximum observed plasma concentration of the study drug
Part A (Dose Escalation) and Part B (Dose Optimisation)
Measured: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts), at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
Pharmacokinetics of AZD0022: AuClast (Area Under the Plasma Contentration-Time Curve to the Last Measurable Plasma Concentration)
A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time.
Part A (Dose Escalation) and Part B (Dose Optimisation)
Measured: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts), at predefined intervals throughout the administration of AZD0022 until Cycle 3 Day 1.
Pharmacokinetics of AZD0022: Terminal elimination half-life (t 1/2)
Terminal elimination half life.
Part A (Dose Escalation) and Part B (Dose Optimisation)
Measured: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts), at predefined intervals throughout the administration of AZD0022 until Cycle 3 Day 1.
Incidence of participants with Adverse events (AEs) and Serious Adverse Events (SAEs).
Determine if treatment with AZD0022 as a monotherapy and in combination with other anticancer agents is safe and tolerable through the assessment of AEs, SAEs, and change from baseline in laboratory parameters, vital signs, and ECGs.
Part C (Potential Efficacy Expansion).
Measured: From time of informed consent, through study completion to 30 days post last dose; an average of 2 years
Number of patients who discontinue AZD0022 due to toxicity
To further assess the safety and tolerability of AZD0022 as a monotherapy and in combination with other anti-cancer agents
Part C (Potential Efficacy Expansion).
Measured: From time of informed consent, through study completion to 30 days post last dose; an average of 2 years
TDT (Time to Discontinuation of Treatment)
To estimate the anti-tumour activity of AZD0022 as a monotherapy and in combination with other anti-cancer agents.
Part C (Potential Efficacy Expansion)
Time from first dose/randomisation date until discontinuation of treatment or death due to any case.
Measured: From first dose until discontinuation of treatment for any reason; approximate duration of 2 years.
TFST (Time to First Subsequent Anti-Cancer)
To estimate the anti-tumour activity of AZD0022 as a monotherapy and in combination with other anti-cancer agents.
Part C (Potential Efficacy Expansion).
Time from first dose/randomisation date until start of first subsequent anti-cancer therapy after discontinuation of study treatment, or death due to any cause.
Measured: From date of first dose until start date of the first subsequent anti-cancer therapy after discontinuation of study treatment, or death; approximate duration of 2 years.
Change in phospho-ERK
To assess KRAS pathway inhibition on treatment with AZD0022 as monotherapy
Module 1 Part A (Dose Escalation), Module 1 Part B (Dose Optimisation) and Module 1 Part C (Potential Efficacy Expansion)*
Module 2 Part A (Dose Escalation), Module 2 Part B (Dose Optimisation) and Module 2 Part C (Potential efficacy expansion)*
*Potential Efficacy Expansion at Sponsor discretion based on emerging data.
Measured: From baseline, at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
Geometric mean and 90% CI for the ratio of fed:fasted in AUClast and Cmax for food-effect cohort.
To characterise the effect of food on AZD0022 as monotherapy
Module 1 Food-effect only
Measured: From first dose, at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
PFS (Progression Free Survival) by BICR
To assess anti-tumour activity of AZD0022 as monotherapy and in combination with other anti-cancer agents
Radiological response evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Module 1 Part B (Dose Optimisation) and Module 1 Part C (Potential Efficacy Expansion)
Module 2 Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion)
Measured: From first dose (non-randomised study parts) or from randomisation (randomised study parts) to progressive disease or death in the absence of disease progression; approximate duration of 2 years
ORR (Objective Response Rate) by BICR
To assess anti-tumour activity of AZD0022 as monotherapy and in combination with other anti-cancer agents
Radiological response evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Module 1 Part B (Dose Optimisation) and Module 1 Part C (Potential Efficacy Expansion)
Module 2 Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion)
Measured: From first dose (non-randomised study parts) or from randomisation (randomised) through study completion; approximate duration of 2 years
DoR (Duration of Rate) by BICR
To assess anti-tumour activity of AZD0022 as monotherapy and in combination with other anti-cancer agents
Radiological response evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Module 1 Part B (Dose Optimisation) and Module 1 Part C (Potential Efficacy Expansion)
Module 2 Part B (Dose Optimisation) and Part C (Potential Efficacy Expansion)
Measured: From the date of first response until date of disease progression (RECIST 1.1) or death in the absence of disease progression; approximate duration of 2 years.
ORR (Objective Response Rate) by Investigator
To assess anti-tumour activity of AZD0022 as monotherapy and in combination with other anti-cancer agents
Radiological response evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1)
Module 1 Part A (Dose Escalation) and Module 1 Part B (Dose Optimisation)
Module 2 Part A (Dose Escalation) and Module 2 Part B (Dose Optimisation)
Measured: From first dose (non-randomised study parts) or from randomisation (randomised) through study completion; approximate duration of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start18 Oct 2024
- Primary completion20 Oct 2025
- Study completion29 Jan 2026
Why it stopped: The decision to cease enrolment and proceed with the early termination of the ALAFOSS 01 (D7080C00001) study was based on strategic company portfolio prioritization.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumoursStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- 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
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06599502
- Sponsor's protocol ID
- D7080C00001
- Acronym
- ALAFOSS-01
- Status last verified
- Mar 2026
- First submitted
- 19 Aug 2024
- Last updated
- 18 Mar 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD0022 Monotherapy and in Combination With Anti-cancer Agents in Participants With Tumours Harbouring a KRASG12D Mutation (ALAFOSS-01)
- ClinicalTrials.gov ID
- NCT06599502
- Acronym / sponsor ID
- ALAFOSS-01 / D7080C00001
- Conditions
- Advanced Solid Tumours, Non-Small Cell Lung Cancer (NSCLC), Pancreatic Ductal Adenocarcinoma (PDAC), Colorectal Cancer (CRC)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The decision to cease enrolment and proceed with the early termination of the ALAFOSS 01 (D7080C00001) study was based on strategic company portfolio prioritization.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 18 Oct 2024 (actual)
- Primary completion
- 20 Oct 2025 (actual)
- Study completion
- 29 Jan 2026 (actual)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
- 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
| Arm | Type | Receives |
|---|---|---|
| Module 1 Part A. Dose Escalation | Experimental | Drug: AZD0022AZD0022 monotherapy |
| Module 1 Part B. Dose Optimisation | Experimental | Drug: AZD0022AZD0022 monotherapy |
| Module 1 Part C. Potential Efficacy Expansion | Experimental | Drug: AZD0022AZD0022 monotherapy |
| Module 1 Part B. Food Effect Cohort | Experimental | Drug: AZD0022AZD0022 monotherapy |
| Module 2 Part A. Dose Escalation | Experimental | Drug: AZD0022, Drug: CetuximabAZD0022 in combination with Cetuximab |
| Module 2 Part B. Dose Optimisation | Experimental | Drug: AZD0022, Drug: CetuximabAZD0022 in combination with Cetuximab |
| Module 2 Part C. Potential Efficacy Expansion | Experimental | Drug: AZD0022, Drug: CetuximabAZD0022 in combination with Cetuximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
- 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.
- 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.
- Documented KRASG12D mutation in tissue or liquid biopsy.
- Provision of a FFPE tumour sample.
Key exclusion criteria (18 listed)
- Any significant laboratory finding or any severe and uncontrolled medical condition.
- 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.
- Spinal cord compression, leptomeningeal disease, or active brain metastases. Asymptomatic brain metastases are allowed
- History of allogenic organ transplantation.
- Participants with any of the following cardiac criteria:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD0022AZD0022 is an oral KRASG12D inhibitor that blocks KRASG12D function in patients with this type of mutation. | Drug | Module 1 Part A. Dose Escalation, Module 1 Part B. Dose Optimisation, Module 1 Part B. Food Effect Cohort, Module 1 Part C. Potential Efficacy Expansion, Module 2 Part A. Dose Escalation, Module 2 Part B. Dose Optimisation, Module 2 Part C. Potential Efficacy Expansion |
| CetuximabCetuximab (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 | Drug | Module 2 Part A. Dose Escalation, Module 2 Part B. Dose Optimisation, Module 2 Part C. Potential Efficacy Expansion |
Primary outcome
Incidence of participants with Dose-Limiting Toxicity (DLT), Adverse events (AEs) and Serious Adverse Events (SAEs).
Time frame: From time of informed consent, through study completion to 30 days post last dose; an average of 2 years
Determine if treatment with AZD0022 as a monotherapy and in combination with other anti-cancer agents is safe and tolerable through the assessment of DLTs, AEs, SAEs, and change from baseline in laboratory parameters, vital signs, and ECGs. Part A (Dose Escalation) and Part B (Dose Optimisation). DLTs only applicable for Part A.
Number of patients who discontinue AZD0022 due to toxicity
Time frame: From time of informed consent to 30 days post last dose
To investigate the safety and tolerability of AZD0022 as a monotherapy and in combination with other anti-cancer agents in participants with advanced tumours harbouring a KRASG12D mutation Part A (Dose Escalation) and Part B (Dose Optimisation)
ORR (Objective Response Rate)
Time frame: Time from first dose of AZD002 through study completion; approximate duration of 2 years
Evaluated according to RECIST v1.1 (Response Evaluation Criteria in Solid Tumours Version 1.1) Part C (Potential Efficacy Expansion) Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR)
23 secondary outcomes
CR rate (Complete Response)
Time frame: From first dose (non-randomised study parts) or from randomisation (randomised) through study completion; approximate duration of 2 years
DoR (Duration of Response)
Time frame: From the date of first response until date of disease progression (RECIST 1.1) or death in the absence of disease progression; approximate duration of 2 years.
DCR (Disease Control Rate)
Time frame: From first dose (non-randomised study parts) or from randomisation (randomised) until progression. For each patient, this is expected to be at 12 weeks
DRR (Durable Response Rate)
Time frame: From first documented response up until progression, or the last evaluable assessment in the absence of progression; approximate duration of 2 years.
TTR (Time to Response)
Time frame: From first dose (non-randomised study parts) or from randomisation (randomised study parts) until the date of documented objective response; approximate duration of 2 years.
PFS (Progression Free Survival)
Time frame: 'From first dose (non-randomised study parts) or from randomisation (randomised study parts) to progressive disease or death in the absence of disease progression; approximate duration of 2 years
Change in tumour size
Time frame: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised), at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
OS (Overall Survival)
Time frame: From first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts) to death; approximate duration of 2 years.
Complete Molecular Response (cMR).
Time frame: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts), at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
Pharmacokinetics of AZD0022: Maximum plasma concentration of the study drug (Cmax)
Time frame: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts), at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
Pharmacokinetics of AZD0022: Time to maximum plasma concentration of the study drug (T-max)
Time frame: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts), at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
Pharmacokinetics of AZD0022: AuClast (Area Under the Plasma Contentration-Time Curve to the Last Measurable Plasma Concentration)
Time frame: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts), at predefined intervals throughout the administration of AZD0022 until Cycle 3 Day 1.
Pharmacokinetics of AZD0022: Terminal elimination half-life (t 1/2)
Time frame: From the first dose of study intervention (non-randomised study parts) or from randomisation (randomised study parts), at predefined intervals throughout the administration of AZD0022 until Cycle 3 Day 1.
Incidence of participants with Adverse events (AEs) and Serious Adverse Events (SAEs).
Time frame: From time of informed consent, through study completion to 30 days post last dose; an average of 2 years
Number of patients who discontinue AZD0022 due to toxicity
Time frame: From time of informed consent, through study completion to 30 days post last dose; an average of 2 years
TDT (Time to Discontinuation of Treatment)
Time frame: From first dose until discontinuation of treatment for any reason; approximate duration of 2 years.
TFST (Time to First Subsequent Anti-Cancer)
Time frame: From date of first dose until start date of the first subsequent anti-cancer therapy after discontinuation of study treatment, or death; approximate duration of 2 years.
Change in phospho-ERK
Time frame: From baseline, at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
Geometric mean and 90% CI for the ratio of fed:fasted in AUClast and Cmax for food-effect cohort.
Time frame: From first dose, at predefined intervals throughout the administration of AZD0022; approximate duration of 2 years.
PFS (Progression Free Survival) by BICR
Time frame: From first dose (non-randomised study parts) or from randomisation (randomised study parts) to progressive disease or death in the absence of disease progression; approximate duration of 2 years
ORR (Objective Response Rate) by BICR
Time frame: From first dose (non-randomised study parts) or from randomisation (randomised) through study completion; approximate duration of 2 years
DoR (Duration of Rate) by BICR
Time frame: From the date of first response until date of disease progression (RECIST 1.1) or death in the absence of disease progression; approximate duration of 2 years.
ORR (Objective Response Rate) by Investigator
Time frame: From first dose (non-randomised study parts) or from randomisation (randomised) through study completion; approximate duration of 2 years
Results and safety
The study was stopped early (reason given: The decision to cease enrolment and proceed with the early termination of the ALAFOSS 01 (D7080C00001) study was based on strategic company portfolio prioritization.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2026.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD0022 and Cetuximab in people with Advanced Solid Tumours and Non-Small Cell Lung Cancer (NSCLC), run by AstraZeneca at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Australia, Japan, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The decision to cease enrolment and proceed with the early termination of the ALAFOSS 01 (D7080C00001) study was based on strategic company portfolio prioritization.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of participants with Dose-Limiting Toxicity (DLT), Adverse events (AEs) and Serious Adverse Events (SAEs). (time frame: From time of informed consent, through study completion to 30 days post last dose; an average of 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2026.