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Investigating AZD0022 for KRASG12D Mutant Tumors

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)

Phase1; Phase2 Interventional AstraZeneca · NCT06599502

This study is testing a new drug called AZD0022 to see if it can help adults with tumors that have a specific KRASG12D mutation, both on its own and when used with other cancer treatments.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment430 (estimated)
Ages18 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionschemotherapy, immunotherapy, radiation, Cetuximab
Locations43 sites (Duarte, California and 42 other locations)
Trial IDNCT06599502 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, open-label, multi-centre study assessing the safety, tolerability, pharmacokinetics, and preliminary efficacy of AZD0022, both as a monotherapy and in combination with other anti-cancer agents like Cetuximab, in adult participants with tumors harboring a KRASG12D mutation. The study consists of two modules: the first module focuses on AZD0022 alone, while the second module evaluates its effectiveness when combined with other treatments. Each module includes three parts: dose escalation, dose optimization, and potential efficacy expansion.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with confirmed metastatic or locally advanced tumors harboring a KRASG12D mutation who have progressed on or are intolerant to standard therapies.

Not a fit: Patients without a documented KRASG12D mutation or those who have not progressed on standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors that have the KRASG12D mutation.

How similar studies have performed: While this approach is novel in targeting KRASG12D mutations specifically, similar studies targeting other KRAS mutations have shown promising results.

Eligibility criteria

Show full inclusion / exclusion 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

Where this trial is running

Duarte, California and 42 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
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Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.