Recurrent/Metastatic Head and Neck Squamous Cell CarcinomaPhase 2NCT05721443
Cetuximab Plus Dalpicilib in Patients With HPV Negative, PD-1 Resistant R/M HNSCC
A Phase 2 study testing Dalpiciclib+cetuximab in people with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University at 1 site in China.
Trial summary
This study is the first clinical study in PD-1 resistant patients with head and neck squamous cell carcinoma with drugs targeting EGFR signaling pathway combined with CDK4/6 inhibitors, which explores the new combination therapies urgently needed in clinical practice and lays a foundation for subsequent studies, with… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Dalpiciclib+cetuximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2022to 1 Nov 2025
- Phase
- Phase 2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years, both sexes.
- Patients with histologically confirmed post-surgical recurrent/metastatic or locally advanced inoperable surgically resectable squamous cell carcinoma of the head and neck with measurable lesions (spiral CT scan ≥ 10 mm, meeting RECIST 1.1 criteria).
- Have received at least 1 cycle of prior PD-1 immunotherapy with imaging confirmation of progression or clinician determination of no continued benefit from treatment; provided that this is completed at least 4 weeks prior to the first dose of study drug and all associated toxic events have returned to normal or grade I or less as defined by CTCAE 4.03 classification.
- HPV viral testing determined to be negative, using the IHC method.
- Availability of tumor tissue (paraffin specimens less than 2 years old or fresh tumor tissue) for detection of PD-L1 and CDK4-related genes.
- ECOG score of 0 or 1.
- Expected survival of ≥ 12 weeks.
- Normal major organ function within 2 weeks prior to treatment, i.e., meeting the following criteria：Bone marrow function: hemoglobin ≥ 100 g/L without transfusion or colony-stimulating factor support therapy, white blood cell count ≥ 4.0*10^9/L or neutrophil count ≥ 2.0*10^9/L, and platelet count ≥ 100*10^9/L; Liver: serum total bilirubin level ≤ 1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 times the upper limit of normal; Renal: blood creatinine level below 1.5 times the upper limit of normal or creatinine clearance ≥ 60 ml/min and urea nitrogen ≤ 200 mg/L; Urine protein <+, or if urine protein + then total 24-hour protein must be <500mg; Blood glucose: within normal range and/or with diabetes in treatment but under stable glycemic control; Pulmonary function: baseline FEV1 of at least 2L; if baseline FEV1 <2L then FEV1 >800ml expected post-surgery as assessed by a surgical specialist; Cardiac function: no myocardial infarction within 1 year; no unstable angina; no symptomatic severe arrhythmias; no cardiac insufficiency.
Who cannot join
- Patients previously treated with cetuximab or other anti-EGFR monoclonal antibodies or small molecule tyrosine kinase inhibitors.
- Patients who are currently receiving antineoplastic therapy.
- Patients who have participated or are participating in a clinical trial of another drug/therapy within 4 weeks prior to the first dose of the study drug.
- Patients who have received hematopoietic stimulating factors, such as granulocyte colony-stimulating factor (G-CSF), erythropoietin, etc., within 1 week prior to the first dose of the study drug.
- Positive HIV antibody or syphilis spirochete antibody test results.
- Patients with active hepatitis B or C: If positive for HBsAg or HBcAb, additional HBV DNA testing (results above the upper limit of the normal range). If HCV antibody test result is positive, add HCV RNA test (result above the upper limit of the normal range).
Show all 15Show fewer
- Known hypersensitivity to recombinant humanized EGFR monoclonal antibody drugs and their components.
- Massive pleural or ascites fluid with clinical symptoms and requiring symptomatic management.
- Active lung disease (interstitial pneumonia, pneumonia, obstructive lung disease, asthma) or a history of active tuberculosis.
- Has any uncontrollable clinical problem, including but not limited to: Persistent or active (severe) infection; Poorly controlled diabetes mellitus; Cardiac disease (Class III/IV congestive heart failure or heart block as defined by the New York Heart Association); Deep vein thrombosis or pulmonary embolism; myocardial infarction; severe or unstable arrhythmia or angina; percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass grafting; cerebrovascular accident, transient ischemic attack, cerebral embolism within 6 months prior to first dose.
- Previous stem cell transplantation or organ transplantation.
- Those with a history of psychotropic substance abuse and unable to abstain or a history of psychiatric disorders.
- Other serious, acute or chronic medical conditions or abnormalities in laboratory tests that, in the judgment of the investigator, may increase the risk associated with study participation or may interfere with the interpretation of study results.
- Patients who, in the judgment of the investigator, have poor compliance or other conditions that make them unsuitable for participation in this trial.
- Patients with a history of other malignancies within five years.
Trial locations and contacts
1 site in 1 country.
China1 site
the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200011
About this study
Official title: Cetuximab Plus Dalpicilib in the Second-line Treatment of Patients With HPV Negative, PD-1 Resistant Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: an Open-label,Single Arm,Phase 2 Trial
This study is the first clinical study in PD-1 resistant patients with head and neck squamous cell carcinoma with drugs targeting EGFR signaling pathway combined with CDK4/6 inhibitors, which explores the new combination therapies urgently needed in clinical practice and lays a foundation for subsequent studies, with important scientific research significance and clinical value.
Read the detailed description
Head and neck cancer is the sixth most common cancer in the world, with more than 550,000 incidences and 300,000 deaths per year worldwide. more than 95% of head and neck cancers are squamous cell carcinomas, and head and neck squamous cell carcinoma (HNSCC) has a devastating and HNSCC affects the quality of life of patients by damaging and affecting their appearance and basic physical, sensory and speech functions. Due to the difficulty of early detection, more than 60% of head and neck squamous cell carcinoma patients are already at locally advanced stage when detected, and the prognosis of locally advanced head and neck carcinoma is poor, and even after receiving aggressive treatment, it is prone to local recurrence and distant metastasis after treatment.
About 25% of patients with squamous head and neck cancer are associated with human papillomavirus (HPV) infection, of which the most common subtype is HPV 16, accounting for more than 80% of all HPV-induced head and neck cancers. HPV infection suppresses the function of oncogenes TP53 and RB, and promotes immune escape and promote the development of head and neck cancer. In China, more than 70% of head and neck squamous carcinomas are not associated with HPV infection, and compared with HPV-associated HNSCC, HPV-negative HNSCC has a lower response rate to treatment and the overall prognosis of patients is worse.
Head and neck squamous cell carcinoma has a high rate of Treg cell as well as NK cell infiltration in the tumor microenvironment, forming an immunosuppressive tumor microenvironment and is a group of malignancies with high immunodeficiency. Studies have shown high levels of PD-L1 expression in tumor tissue in 46%-100% of HNSCC. Therefore, blockade of immune checkpoint inhibitors represented by PD-L1/PD-1 is a theoretically feasible therapeutic approach for the treatment of HNSCC. The results of previous clinical trials of immunotherapy in patients with recurrent or metastatic head and neck squamous carcinoma showed that anti-PD-1 antibodies led to durable remission and improved survival in patients with either first- or second-line therapy. The KEYNOTE-048 study confirmed that pembrolizumab in combination with chemotherapy prolonged overall survival in patients with recurrent or metastatic head and neck squamous carcinoma and in 2021 recommended by CSCO guidelines as a first-line expert recommendation for the first-line treatment of recurrent or metastatic head and neck squamous carcinoma (Level of Evidence 1A). However, patients with recurrent or metastatic head and neck squamous carcinoma after failure of first-line applied anti-PD-1 therapy enter second-line therapy The current guideline recommended second-line treatment regimens are cetuximab, afatinib or methotrexate, but the overall prognosis of patients is poor, the drug response rate is not high, the highest objective remission rate reported in the literature is only 13%, and the time to tumor progression is only 2.3 months, therefore, exploring new second-line treatment options for patients with recurrent or metastatic head and neck squamous carcinoma after failure of anti-PD-1 therapy is a pressing clinical need.
In addition, the results of previous clinical trials showed that HPV-negative HNSCC had poorer sensitivity and prognosis to immunotherapy than HPV-associated HNSCC. In KEYNOTE-012, patients with HPV-positive HNSCC had higher objective remission (32% vs 14%) and progression-free survival (4 months vs 2 months) with pablizumab, and similar results were confirmed by KEYNOTE-055. Furthermore, in a meta-analysis of 11 studies, HPV-positive HNSCC patients showed a 1.29-fold higher response rate to immunotherapy and a twofold higher overall survival (11.5 months vs. 6.3 months) than HPV-negative HNSCC patients.
There are a large number of ongoing clinical trials of combination targeted therapies and immunotherapies. The basic rationale supporting these combinations is that the two therapies combine different immunological and tumor biological mechanisms that enhance antitumor activity; in addition, some evidence suggests that targeted therapies can enhance certain aspects of the "cancer-immune cycle" (e.g., tumor antigenicity, T-cell initiation/transport/infiltration, etc.) to immunotherapy. In addition, it has been shown that targeted therapies can synergistically enhance certain aspects of the "cancer-immune cycle" (e.g., tumor antigenicity, T cell initiation/transport/infiltration, etc.) for immunotherapy. CDK4, one of the key cell cycle regulators, is involved in cell growth, proliferation, dormancy or apoptosis by binding to cell cycle protein D, which regulates the transition from G1 phase (pre-DNA synthesis) to S phase (DNA synthesis). In 2013, the US Food and Drug Administration (FDA) approved the CDK4 inhibitor Palbociclib as a breakthrough new drug for the treatment of advanced breast cancer, and the National Comprehensive Cancer Network (NCCN) guidelines recommend piperacillin in combination with an aromatase inhibitor as a first-line treatment option for HR+/HER2-advanced or metastatic breast cancer. Recent studies have found that CDK4 gene inhibition in combination with afatinib synergistically enhances the inhibition of the PI3k pathway in head and neck cancer cells, which in turn reduces tumor proliferation, providing a strong rationale for combination therapy.
P16 deletion is a hallmark event in HPV-negative HNSCC patients, and p16 inactivation would lead to CDK4/6 hyperactivation, making CDK4/6 theoretically a potential target for HPV-negative HNSCC. Some progress has been made with CDK4/6 inhibitors in HPV-negative head and neck squamous carcinoma. In a multicenter, multicohort phase II clinical trial, cohort 1 enrolled in first-line treatment of platinum-resistant HPV-negative patients with recurrent/metastatic HNSCC, and cohort 2 enrolled in first-line treatment of cetuximab-resistant HPV-negative cohort 3 enrolled patients with cetuximab-resistant HPV-positive recurrent/metastatic oropharyngeal cancer, and all three groups received Palbociclib in combination with cetuximab, showing objective remission rates of up to 39% in cohort 1 and 19% in cohort 2, but only 4% in cohort 3, indicating that CDK4/6 inhibitors in combination with cetuximab has a promising application in the treatment of HPV-negative HNSCC.
This clinical study involved dalpiciclib, which was developed by Jiangsu Hengrui Pharmaceutical Co. In December 2021, the State Drug Administration approved the drug in combination with fulvestrant for patients with recurrent or metastatic breast cancer with hormone receptor-positive, human epidermal growth factor receptor 2-negative disease progression after previous endocrine therapy through a priority review and approval process. Patients. Preclinical studies have shown that dalpiciclib has comparable in vivo efficacy and safety compared to its foreign counterparts.
This study is also the first clinical study of a drug targeting CDK4/6 in combination with cetuximab for the treatment of HPV-negative head and neck squamous carcinoma after progression of PD-1 therapy in China, which is of great scientific significance and clinical value in exploring new combination therapies for HPV-negative patients, a population with poor clinical outcome, and laying the foundation for subsequent studies.
- Being tested
- Dalpiciclib+cetuximab
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dalpiciclib+cetuximabDrug
The starting dose of cetuximab is 400 mg/m2 with a drip duration of 120 minutes, and the drip rate should be controlled to less than 5 ml/min. The maintenance dose is 250 mg/m2, with a drip duration of not less than 60 minutes, administered weekly; H1-blocker desensitization pretreatment is given in advance of dosing.
The recommended dose of Dalpiciclib is 150 mg once daily for 21 consecutive days, followed by 7 days of discontinuation (3/1 dosing regimen), for a 28-day treatment cycle. Take the medication at approximately the same time each day. If the patient vomits or misses a dose, it should not be made up on the same day. The next dose should be taken as usual.
Subjects will continue treatment with cetuximab in combination with Dalpiciclib until termination criteria are met.
| Study group | Role | What they receive |
|---|---|---|
| Dalpiciclib+cetuximab | Experimental | The starting dose of cetuximab is 400 mg/m2 with a drip duration of 120 minutes, and the drip rate should be controlled to less than 5 ml/min. The maintenance dose is 250 mg/m2, with a drip duration of not less than 60 minutes, administered weekly; H1-blocker desensitization pretreatment is given in advance of dosing.
The recommended dose of Dalpiciclib is 150 mg once daily for 21 consecutive days, followed by 7 days of discontinuation (3/1 dosing regimen), for a 28-day treatment cycle. Take the medication at approximately the same time each day. If the patient vomits or misses a dose, it should not be made up on the same day. The next dose should be taken as usual.
Subjects will continue treatment with cetuximab in combination with Dalpiciclib until termination criteria are met. Receives: Drug: Dalpiciclib+cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
objective response rate
ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR:
disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.
Measured: 12 months
Secondary outcomes (4)
overall survival
OS was defined as the time from enrollment to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up.
Measured: 12 months
Progression Free Survival Per RECIST 1.1
PFS was defined as the time from enrollment to the first documented PD per RECIST 1.1, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD
Measured: 12 months
Number of Participants Experiencing an Adverse Event (AE).
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE was reported for each treatment arm.
Measured: 12 months
Quality of life#EORTC QLQ-C30 scale#
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the GHS question "How would you rate your overall health during the past week?" (Item 29) and the QoL question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent).
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2023
- Study start1 Dec 2022
- Primary completion1 Nov 2024
- Study completion1 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent/Metastatic Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Historical data showed that the ORR for cetuximab monotherapy as second-line treatment was 13%. The study adopted a Simon's two-stage design to minimize the number of subjects exposed to ineffective treatment. Based on the expected ORR of 33% for dalpiciclib combined with cetuximab, assuming α of 0.05 (two-sided) and power of 80%, we anticipated to enroll 14 participants in the first stage. If the number of responders (CR+PR) was no more than 1, the study would be terminated due to insufficient efficacy. If more than one participant obtained CR or PR, the study would additionally recruit another 12 participants in the second stage. A total of 26 participants were anticipated to enroll. If the total number of responders (CR + PR) across both stages was more than 6, the combination therapy would be considered effective.
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, ren guoxin, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
- Investigators
- Yue He, M.D., Principal investigator, the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05721443
- Sponsor's protocol ID
- SH9H-2022-T252-1
- Status last verified
- Jun 2026
- First submitted
- 9 Nov 2022
- Last updated
- 18 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 18 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cetuximab Plus Dalpicilib in the Second-line Treatment of Patients With HPV Negative, PD-1 Resistant Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: an Open-label,Single Arm,Phase 2 Trial
- ClinicalTrials.gov ID
- NCT05721443
- Acronym / sponsor ID
- SH9H-2022-T252-1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong UniversityUniversity, hospital or other
- Study start
- 1 Dec 2022 (actual)
- Primary completion
- 1 Nov 2024 (actual)
- Study completion
- 1 Nov 2025 (actual)
- First posted
- 10 Feb 2023 (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 study is the first clinical study in PD-1 resistant patients with head and neck squamous cell carcinoma with drugs targeting EGFR signaling pathway combined with CDK4/6 inhibitors, which explores the new combination therapies urgently needed in clinical practice and lays a foundation for subsequent studies, with important scientific research significance and clinical value.
Detailed description
Head and neck cancer is the sixth most common cancer in the world, with more than 550,000 incidences and 300,000 deaths per year worldwide. more than 95% of head and neck cancers are squamous cell carcinomas, and head and neck squamous cell carcinoma (HNSCC) has a devastating and HNSCC affects the quality of life of patients by damaging and affecting their appearance and basic physical, sensory and speech functions. Due to the difficulty of early detection, more than 60% of head and neck squamous cell carcinoma patients are already at locally advanced stage when detected, and the prognosis of locally advanced head and neck carcinoma is poor, and even after receiving aggressive treatment, it is prone to local recurrence and distant metastasis after treatment.
About 25% of patients with squamous head and neck cancer are associated with human papillomavirus (HPV) infection, of which the most common subtype is HPV 16, accounting for more than 80% of all HPV-induced head and neck cancers. HPV infection suppresses the function of oncogenes TP53 and RB, and promotes immune escape and promote the development of head and neck cancer. In China, more than 70% of head and neck squamous carcinomas are not associated with HPV infection, and compared with HPV-associated HNSCC, HPV-negative HNSCC has a lower response rate to treatment and the overall prognosis of patients is worse.
Head and neck squamous cell carcinoma has a high rate of Treg cell as well as NK cell infiltration in the tumor microenvironment, forming an immunosuppressive tumor microenvironment and is a group of malignancies with high immunodeficiency. Studies have shown high levels of PD-L1 expression in tumor tissue in 46%-100% of HNSCC. Therefore, blockade of immune checkpoint inhibitors represented by PD-L1/PD-1 is a theoretically feasible therapeutic approach for the treatment of HNSCC. The results of previous clinical trials of immunotherapy in patients with recurrent or metastatic head and neck squamous carcinoma showed that anti-PD-1 antibodies led to durable remission and improved survival in patients with either first- or second-line therapy. The KEYNOTE-048 study confirmed that pembrolizumab in combination with chemotherapy prolonged overall survival in patients with recurrent or metastatic head and neck squamous carcinoma and in 2021 recommended by CSCO guidelines as a first-line expert recommendation for the first-line treatment of recurrent or metastatic head and neck squamous carcinoma (Level of Evidence 1A). However, patients with recurrent or metastatic head and neck squamous carcinoma after failure of first-line applied anti-PD-1 therapy enter second-line therapy The current guideline recommended second-line treatment regimens are cetuximab, afatinib or methotrexate, but the overall prognosis of patients is poor, the drug response rate is not high, the highest objective remission rate reported in the literature is only 13%, and the time to tumor progression is only 2.3 months, therefore, exploring new second-line treatment options for patients with recurrent or metastatic head and neck squamous carcinoma after failure of anti-PD-1 therapy is a pressing clinical need.
In addition, the results of previous clinical trials showed that HPV-negative HNSCC had poorer sensitivity and prognosis to immunotherapy than HPV-associated HNSCC. In KEYNOTE-012, patients with HPV-positive HNSCC had higher objective remission (32% vs 14%) and progression-free survival (4 months vs 2 months) with pablizumab, and similar results were confirmed by KEYNOTE-055. Furthermore, in a meta-analysis of 11 studies, HPV-positive HNSCC patients showed a 1.29-fold higher response rate to immunotherapy and a twofold higher overall survival (11.5 months vs. 6.3 months) than HPV-negative HNSCC patients.
There are a large number of ongoing clinical trials of combination targeted therapies and immunotherapies. The basic rationale supporting these combinations is that the two therapies combine different immunological and tumor biological mechanisms that enhance antitumor activity; in addition, some evidence suggests that targeted therapies can enhance certain aspects of the "cancer-immune cycle" (e.g., tumor antigenicity, T-cell initiation/transport/infiltration, etc.) to immunotherapy. In addition, it has been shown that targeted therapies can synergistically enhance certain aspects of the "cancer-immune cycle" (e.g., tumor antigenicity, T cell initiation/transport/infiltration, etc.) for immunotherapy. CDK4, one of the key cell cycle regulators, is involved in cell growth, proliferation, dormancy or apoptosis by binding to cell cycle protein D, which regulates the transition from G1 phase (pre-DNA synthesis) to S phase (DNA synthesis). In 2013, the US Food and Drug Administration (FDA) approved the CDK4 inhibitor Palbociclib as a breakthrough new drug for the treatment of advanced breast cancer, and the National Comprehensive Cancer Network (NCCN) guidelines recommend piperacillin in combination with an aromatase inhibitor as a first-line treatment option for HR+/HER2-advanced or metastatic breast cancer. Recent studies have found that CDK4 gene inhibition in combination with afatinib synergistically enhances the inhibition of the PI3k pathway in head and neck cancer cells, which in turn reduces tumor proliferation, providing a strong rationale for combination therapy.
P16 deletion is a hallmark event in HPV-negative HNSCC patients, and p16 inactivation would lead to CDK4/6 hyperactivation, making CDK4/6 theoretically a potential target for HPV-negative HNSCC. Some progress has been made with CDK4/6 inhibitors in HPV-negative head and neck squamous carcinoma. In a multicenter, multicohort phase II clinical trial, cohort 1 enrolled in first-line treatment of platinum-resistant HPV-negative patients with recurrent/metastatic HNSCC, and cohort 2 enrolled in first-line treatment of cetuximab-resistant HPV-negative cohort 3 enrolled patients with cetuximab-resistant HPV-positive recurrent/metastatic oropharyngeal cancer, and all three groups received Palbociclib in combination with cetuximab, showing objective remission rates of up to 39% in cohort 1 and 19% in cohort 2, but only 4% in cohort 3, indicating that CDK4/6 inhibitors in combination with cetuximab has a promising application in the treatment of HPV-negative HNSCC.
This clinical study involved dalpiciclib, which was developed by Jiangsu Hengrui Pharmaceutical Co. In December 2021, the State Drug Administration approved the drug in combination with fulvestrant for patients with recurrent or metastatic breast cancer with hormone receptor-positive, human epidermal growth factor receptor 2-negative disease progression after previous endocrine therapy through a priority review and approval process. Patients. Preclinical studies have shown that dalpiciclib has comparable in vivo efficacy and safety compared to its foreign counterparts.
This study is also the first clinical study of a drug targeting CDK4/6 in combination with cetuximab for the treatment of HPV-negative head and neck squamous carcinoma after progression of PD-1 therapy in China, which is of great scientific significance and clinical value in exploring new combination therapies for HPV-negative patients, a population with poor clinical outcome, and laying the foundation for subsequent studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Historical data showed that the ORR for cetuximab monotherapy as second-line treatment was 13%. The study adopted a Simon's two-stage design to minimize the number of subjects exposed to ineffective treatment. Based on the expected ORR of 33% for dalpiciclib combined with cetuximab, assuming α of 0.05 (two-sided) and power of 80%, we anticipated to enroll 14 participants in the first stage. If the number of responders (CR+PR) was no more than 1, the study would be terminated due to insufficient efficacy. If more than one participant obtained CR or PR, the study would additionally recruit another 12 participants in the second stage. A total of 26 participants were anticipated to enroll. If the total number of responders (CR + PR) across both stages was more than 6, the combination therapy would be considered effective.
| Arm | Type | Receives |
|---|---|---|
| Dalpiciclib+cetuximab | Experimental | Drug: Dalpiciclib+cetuximabThe starting dose of cetuximab is 400 mg/m2 with a drip duration of 120 minutes, and the drip rate should be controlled to less than 5 ml/min. The maintenance dose is 250 mg/m2, with a drip duration of not less than 60 minutes, administered weekly; H1-blocker desensitization pretreatment is given in advance of dosing. The recommended dose of Dalpiciclib is 150 mg once daily for 21 consecutive days, followed by 7 days of discontinuation (3/1 dosing regimen), for a 28-day treatment cycle. Take the medication at approximately the same time each day. If the patient vomits or misses a dose, it should not be made up on the same day. The next dose should be taken as usual. Subjects will continue treatment with cetuximab in combination with Dalpiciclib until termination criteria are met. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18-75 years, both sexes.
- Patients with histologically confirmed post-surgical recurrent/metastatic or locally advanced inoperable surgically resectable squamous cell carcinoma of the head and neck with measurable lesions (spiral CT scan ≥ 10 mm, meeting RECIST 1.1 criteria).
- Have received at least 1 cycle of prior PD-1 immunotherapy with imaging confirmation of progression or clinician determination of no continued benefit from treatment; provided that this is completed at least 4 weeks prior to the first dose of study drug and all associated toxic events have returned to normal or grade I or less as defined by CTCAE 4.03 classification.
- HPV viral testing determined to be negative, using the IHC method.
- Availability of tumor tissue (paraffin specimens less than 2 years old or fresh tumor tissue) for detection of PD-L1 and CDK4-related genes.
Key exclusion criteria (15 listed)
- Patients previously treated with cetuximab or other anti-EGFR monoclonal antibodies or small molecule tyrosine kinase inhibitors.
- Patients who are currently receiving antineoplastic therapy.
- Patients who have participated or are participating in a clinical trial of another drug/therapy within 4 weeks prior to the first dose of the study drug.
- Patients who have received hematopoietic stimulating factors, such as granulocyte colony-stimulating factor (G-CSF), erythropoietin, etc., within 1 week prior to the first dose of the study drug.
- Positive HIV antibody or syphilis spirochete antibody test results.
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 |
|---|---|---|
| Dalpiciclib+cetuximabThe starting dose of cetuximab is 400 mg/m2 with a drip duration of 120 minutes, and the drip rate should be controlled to less than 5 ml/min. The maintenance dose is 250 mg/m2, with a drip duration of not less than 60 minutes, administered weekly; H1-blocker desensitization pretreatment is given in advance of dosing. The recommended dose of Dalpiciclib is 150 mg once daily for 21 consecutive days, followed by 7 days of discontinuation (3/1 dosing regimen), for a 28-day treatment cycle. Take the medication at approximately the same time each day. If the patient vomits or misses a dose, it should not be made up on the same day. The next dose should be taken as usual. Subjects will continue treatment with cetuximab in combination with Dalpiciclib until termination criteria are met. | Drug | Dalpiciclib+cetuximab |
Primary outcome
objective response rate
Time frame: 12 months
ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1.
4 secondary outcomes
overall survival
Time frame: 12 months
Progression Free Survival Per RECIST 1.1
Time frame: 12 months
Number of Participants Experiencing an Adverse Event (AE).
Time frame: 12 months
Quality of life#EORTC QLQ-C30 scale#
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2026.
- Individual participant dataSharing planned: No
Related trials for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
RecruitingPhase 1
A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors
Metastatic Solid Tumor, Recurrent Solid Tumor
RecruitingPhase 3
A Study of Amivantamab in Addition to Standard of Care Agents (SOC) Compared With SOC Alone in Participants With Recurrent/Metastatic Head and Neck Cancer
Squamous Cell Carcinoma of Head and Neck
Active, not recruitingPhase 2/3
Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers
Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Metastatic Head and Neck Squamous Cell Carcinoma
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.
Yue He, M.D. principal investigator
the Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dalpiciclib+cetuximab in people with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong 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 8 inclusion and 15 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: finished, as of the sponsor's last update on 18 Jun 2026. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
objective response rate (time frame: 12 months). 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 Jun 2026.