EGFR Tyrosine Kinase Inhibitors Plus Cyclin-dependent Kinase 4/6 InhibitorPhase 1/2APEAKNCT06947811
A Study of Almonertinib Combined With Palbociclib in Patients With Advanced Solid Tumors Harboring KRAS Mutations
A Phase 1/2 study testing Almonertinib and Palbociclib in people with EGFR Tyrosine Kinase Inhibitors Plus Cyclin-dependent Kinase 4/6 Inhibitor, run by Sun Yat-sen University at 1 site in China.
Trial summary
The main purpose of this study is to evaluate the safety and tolerability of almonertinib combined with palbociclib in patients with advanced solid tumors harboring KRAS gene mutations, and to conduct a preliminary observation of its efficacy Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- EGFR Tyrosine Kinase Inhibitors Plus Cyclin-dependent Kinase 4/6 Inhibitor
- What is being tested?
- Almonertinib and Palbociclib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 1 siteChina
- Study dates
- 9 Jun 2025to Mar 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 18 and ≤ 70 years of age (containing threshold levels), no gender restrictions.
- Eastern Cooperative Oncology Group (ECOG) performance scale 0 - 1.
- Life expectancy of no less than 12 weeks. Histologically or cytologically confirmed advanced solid tumors (including but not limited to lung cancer, pancreatic cancer, colorectal cancer, etc.),who meet at least one of the following criteria：
- tissue and/or ctDNA samples with KRAS mutation (including but not limited to G12C，G12D，G13D，G12V，G12S, etc.) .
- failure of prior standard therapy or no standard treatment is available.
- Any toxicities related to prior anticancer therapy must have recovered to ≤ Grade 1 (excluding alopecia).
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- Have not received chemotherapy or other targeted therapies previously.
- -note: Therapies administered during the neoadjuvant treatment phase are not counted as prior treatment regimens; patients who experience disease recurrence within 6 months after completion of adjuvant therapy will have the adjuvant therapy considered as first-line therapy and are not eligible for this study; for recurrence occurring >6 months after completion of adjuvant therapy, the adjuvant therapy will not be counted as a prior treatment regimen.
- Patients who have received prior radiotherapy are eligible for enrollment, provided that: the irradiated area involves <25% of the bone marrow (Cristy and Eckerman 1987), and no whole pelvic or thoracic irradiation has been administered; prior radiotherapy must have been completed at least 4 weeks before study enrollment, any acute toxicities related to previous radiotherapy must have resolved; previously irradiated lesions cannot be considered measurable target lesions unless documented progression is observed after the last radiotherapy session.
- Adequate organ function prior to the first dose of the study drug, with cardiac, hematological, hepatic, and renal functions meeting protocol-specified requirements as defined by the following criteria:
- Hematological laboratory tests must meet the following criteria:
- ANC≥1.5×109/L；
- PLT≥100×109/L；
- Hb≥100g/L.
- The biochemical examination must meet the following criteria:
- TBIL<1.5×ULN；
- ALT、AST and ALP<2.5×ULN；
- BUN and Cr≤1×ULN or endogenous creatinine clearance rate≥50ml/min（Cockcroft-Gault formula）.
- Female subjects of childbearing potential must have either practiced reliable contraceptive methods or undergone a pregnancy test (serum or urine) within 7 days prior to enrollment with negative results, and must be willing to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the investigational drug. Male subjects must agree to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the investigational drug, or have been surgically sterilized.
- Subjects must voluntarily participate in the study, sign an informed consent form, demonstrate good compliance, and actively cooperate with follow-up procedures.
- Subjects are requested to provide, whenever possible, previous tumor tissue paraffin blocks (or 5-15 pathological biopsy sections [unstained slides]) and peripheral blood specimens (10ml), and to cooperate with investigators during treatment for tumor biopsy sampling when feasible, to support exploratory research on tumor biomarker detection.
Who cannot join
- Patients presenting with any of the following criteria will be excluded from the study:
- Exclusion applies to patients who had symptomatic CNS metastases, leptomeningeal metastases, or spinal cord compression caused by metastatic lesions prior to signing the informed consent form.
- Patients with prior or current use of CDK4/6-targeted anticancer agents.
- Molecular targeted therapy or radiotherapy within 2 weeks prior to screening; Chemotherapy or immunotherapy within 3 weeks prior to screening; Nitrosoureas or mitomycin administration within 6 weeks prior to screening; Prior radical radiotherapy involving ≥25% of bone marrow, inclusion eligibility subject to investigator evaluation.
- Major surgery performed within 6 weeks prior to screening, or planned major surgery within 12 weeks after initiation of the investigational drug.
- Patients who have participated in other clinical studies with active treatment exposure within 28 days before the first investigational drug dose are ineligible.
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- Third-space fluid accumulations refractory to drainage or therapeutic interventions exist (such as massive pleural effusions, ascites, and pericardial effusions).
- Active inflammatory bowel disease, chronic diarrhea, intestinal obstruction, dysphagia, or the presence of multiple factors that impair drug administration and absorption.
- Uncontrolled electrolyte disturbances (e.g., hypocalcemia, hypokalemia, hypomagnesemia).
- Individuals with allergic predisposition or a history of severe allergic reactions.
- Active hepatitis B virus (HBV) infection; active hepatitis C virus (HCV) infection; history of immunodeficiency.
- Documented long QT syndrome (congenital/acquired) or familial LQTS with genetic confirmation; significant ventricular arrhythmias (e.g., sustained VT/VF), ongoing antiarrhythmic therapy, or ICD implantation; grade 3+ (CTCAE v5.0) cardio/cerebrovascular events within 6 months pre-dosing; NYHA functional class III-IV.
- Suffers from severe lung disease (interstitial lung disease, severe chronic obstructive pulmonary disease [COPD], severe pulmonary insufficiency, and a history of symptomatic bronchospasm).
- Pregnant or lactating women; women of childbearing potential with a positive baseline pregnancy test; and women of childbearing age or male patients with partners of childbearing age who are unwilling to use effective contraception throughout the trial period.
- Presence of concomitant diseases deemed by the investigator to pose significant risks to patient safety or compromise study completion.
- Documented history of neurological or psychiatric disorders, including epilepsy or dementia.
- Other conditions deemed by the investigator to preclude safe and appropriate study participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510000
Sun Yat-sen University Cancer Center, 86-20-8734 2482 ext. Study Principa, zhaohy@sysucc.org.cn
About this study
Official title: A Multicenter, Open-Label, Single-Arm, Phase Ib/II Clinical Study of Almonertinib Combined With Palbociclib in the Treatment of Patients With KRAS Mutations-Positive Advanced Solid Tumors
The main purpose of this study is to evaluate the safety and tolerability of almonertinib combined with palbociclib in patients with advanced solid tumors harboring KRAS gene mutations, and to conduct a preliminary observation of its efficacy
Read the detailed description
The main purpose of this study is to evaluate the safety and tolerability of almonertinib combined with palbociclib in patients with advanced solid tumors harboring KRAS gene mutations, and to conduct a preliminary observation of its efficacy
- Being tested
- Almonertinib, Palbociclib
- Keywords
- EGFR Tyrosine Kinase Inhibitors, Cyclin-dependent kinase 4/6 inhibitor, solid tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlmonertinibDrug
Patients will be treated with Almonertinib, 110 mg p.o., daily
PalbociclibDrug
Patients will be treated with Palbociclib, 125 mg(dose determined from Part one of study) p.o., daily
| Study group | Role | What they receive |
|---|---|---|
| Almonertinib + Palbociclib | Experimental | Part 1: Phase I open-label dose-escalation study. The dose of Ameitinib (110mg) remains unchanged, while the administration frequency of palbociclib will be adjusted based on patient tolerance. Dosing regimen: Palbociclib capsules 125mg, orally once daily (qd) for 21 consecutive days followed by a 7-day break + Ameitinib 110mg, orally once daily (qd); administered on an empty stomach, with each treatment cycle lasting 4 weeks.
Part 2: Single-arm Phase II clinical study, based on the dosing regimen of palbociclib capsules determined during the safety run-in phase. Dosing regimen: Palbociclib capsules 125mg, orally once daily (qd), administered on an empty stomach for 21 consecutive days followed by a 7-day break (tentative) + Ameitinib 110mg, orally once daily (qd), administered on an empty stomach for 28 consecutive days; each treatment cycle lasts 4 weeks. Receives: Drug: Almonertinib; Drug: Palbociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
Measured: Safety and Tolerability Assessment : Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 [Time Frame: Randomization to Measured Progressive Disease (Estimated as 50 Months)]
Objective Response Rate (ORR)
Measured: Objective Response Rate (ORR) [Time Frame: Randomization to Disease Progression (Estimated as 42 Months)]
Secondary outcomes (1)
Progression Free Survival (PFS)
Measured: Progression Free Survival (PFS) [Time Frame: Randomization to Measured Progressive Disease or Death from Any Cause (Estimated as 42 Months)]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2025
- Study start9 Jun 2025 (estimated)
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EGFR Tyrosine Kinase Inhibitors Plus Cyclin-dependent Kinase 4/6 InhibitorStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 71 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hongyun Zhao, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06947811
- Sponsor's protocol ID
- 2025-FXY-058
- Acronym
- APEAK
- Status last verified
- Jun 2025
- First submitted
- 14 Apr 2025
- Last updated
- 4 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label, Single-Arm, Phase Ib/II Clinical Study of Almonertinib Combined With Palbociclib in the Treatment of Patients With KRAS Mutations-Positive Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT06947811
- Acronym / sponsor ID
- APEAK / 2025-FXY-058
- Keywords
- EGFR Tyrosine Kinase Inhibitors, Cyclin-dependent kinase 4/6 inhibitor, solid tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 71 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 9 Jun 2025 (estimated)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 27 Apr 2025 (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.
The main purpose of this study is to evaluate the safety and tolerability of almonertinib combined with palbociclib in patients with advanced solid tumors harboring KRAS gene mutations, and to conduct a preliminary observation of its efficacy
Detailed description
The main purpose of this study is to evaluate the safety and tolerability of almonertinib combined with palbociclib in patients with advanced solid tumors harboring KRAS gene mutations, and to conduct a preliminary observation of its efficacy
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Almonertinib + Palbociclib | Experimental | Drug: Almonertinib, Drug: PalbociclibPart 1: Phase I open-label dose-escalation study. The dose of Ameitinib (110mg) remains unchanged, while the administration frequency of palbociclib will be adjusted based on patient tolerance. Dosing regimen: Palbociclib capsules 125mg, orally once daily (qd) for 21 consecutive days followed by a 7-day break + Ameitinib 110mg, orally once daily (qd); administered on an empty stomach, with each treatment cycle lasting 4 weeks. Part 2: Single-arm Phase II clinical study, based on the dosing regimen of palbociclib capsules determined during the safety run-in phase. Dosing regimen: Palbociclib capsules 125mg, orally once daily (qd), administered on an empty stomach for 21 consecutive days followed by a 7-day break (tentative) + Ameitinib 110mg, orally once daily (qd), administered on an empty stomach for 28 consecutive days; each treatment cycle lasts 4 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- ≥ 18 and ≤ 70 years of age (containing threshold levels), no gender restrictions.
- Eastern Cooperative Oncology Group (ECOG) performance scale 0 - 1.
- Life expectancy of no less than 12 weeks. Histologically or cytologically confirmed advanced solid tumors (including but not limited to lung cancer, pancreatic cancer, colorectal cancer, etc.),who meet at least one of the following criteria：
- Any toxicities related to prior anticancer therapy must have recovered to ≤ Grade 1 (excluding alopecia).
- Have not received chemotherapy or other targeted therapies previously.
Key exclusion criteria (17 listed)
- Exclusion applies to patients who had symptomatic CNS metastases, leptomeningeal metastases, or spinal cord compression caused by metastatic lesions prior to signing the informed consent form.
- Patients with prior or current use of CDK4/6-targeted anticancer agents.
- Molecular targeted therapy or radiotherapy within 2 weeks prior to screening; Chemotherapy or immunotherapy within 3 weeks prior to screening; Nitrosoureas or mitomycin administration within 6 weeks prior to screening; Prior radical radiotherapy involving ≥25% of bone marrow, inclusion eligibility subject to investigator evaluation.
- Major surgery performed within 6 weeks prior to screening, or planned major surgery within 12 weeks after initiation of the investigational drug.
- Patients who have participated in other clinical studies with active treatment exposure within 28 days before the first investigational drug dose are ineligible.
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 |
|---|---|---|
| AlmonertinibPatients will be treated with Almonertinib, 110 mg p.o., daily | Drug | Almonertinib + Palbociclib |
| PalbociclibPatients will be treated with Palbociclib, 125 mg(dose determined from Part one of study) p.o., daily | Drug | Almonertinib + Palbociclib |
Primary outcome
Safety and Tolerability
Time frame: Safety and Tolerability Assessment : Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 [Time Frame: Randomization to Measured Progressive Disease (Estimated as 50 Months)]
Objective Response Rate (ORR)
Time frame: Objective Response Rate (ORR) [Time Frame: Randomization to Disease Progression (Estimated as 42 Months)]
1 secondary outcome
Progression Free Survival (PFS)
Time frame: Progression Free Survival (PFS) [Time Frame: Randomization to Measured Progressive Disease or Death from Any Cause (Estimated as 42 Months)]
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2025.
- Individual participant dataSharing planned: No
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Almonertinib and Palbociclib in people with EGFR Tyrosine Kinase Inhibitors Plus Cyclin-dependent Kinase 4/6 Inhibitor, run by Sun Yat-sen University at 1 site in China.
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 21 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 4 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hongyun Zhao Hongyun Zhao (86-20-8734 2482, zhaohy@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability (time frame: Safety and Tolerability Assessment : Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 [Time Frame: Randomization to Measured Progressive Disease (Estimated as 50 Months)]). The study lists 2 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 4 Jun 2025.