A Randomized, Open-label, Multicenter, Phase 3 Trial of Ivonescimab Alone or With Ligufalimab Versus Pembrolizumab in First-line Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Plain English Summary

Study Comparing Ivonescimab Alone or Ivonescimab in Combination With Ligufalimab Versus Pembrolizumab for the Treatment of SCCHN is a Phase 3 clinical trial sponsored by Groupe Oncologie Radiotherapie Tete et Cou studying Squamous Cell Carcinoma Head and Neck Cancer (HNSCC). Tests a new cancer drug (Ivonescimab) alone or with another drug (Ligufalimab) compared to a standard treatment (Pembrolizumab) for head and neck cancer. For patients with recurrent or metastatic head and neck cancer who have not received prior systemic anti-tumor therapy. Participation involves receiving infusions of the study drugs every 3 weeks for up to 24 months. Alternative treatments include other immunotherapy drugs and standard chemotherapy. The trial aims to enroll 780 participants.

Official Summary

This is a randomized, open-label, active-comparator-controlled, multi-regional, three-arm, phase 3 study comparing the efficacy and safety of ivonescimab in combination with ligufalimab to pembrolizumab and of ivonescimab alone to pembrolizumab as first-line treatment in patients with recurrent or metastatic (R/M) PD-L1-positive squamous cell carcinoma of the head and neck (HNSCC). The objective of this study is to improve first-line survival in patients with recurrent or metastatic PD-L1-positive HNSCC (CPS ≥ 1). Overall survival (OS) was chosen as the primary endpoint. Patients will receive the following treatment regimens in accordance with the study treatment plan until disease progression, death, intolerable toxicity, or the occurrence of another protocol-specified treatment discontinuation criterion, whichever occurs first. * ARM A: Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W) * ARM B: Ivonescimab (10 mg/kg iv, 60 min ± 10 min infusion, Q3W), and ligufalimab (45 mg/kg iv, 120 min ± 15 min infusion, Q3W). * ARM C (control arm): Pembrolizumab (200 mg iv, 60 min ± 10 min infusion, Q3W). The total duration of treatment is up to 24 months

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible patients are adults aged 18-79 with recurrent or metastatic head and neck cancer. Patients must have a performance status of 0 or 1, expected survival of at least 6 months, and PD-L1 positive tumors. Exclusions include patients with certain primary tumor sites, other malignancies, or prior immunotherapy. Age and health requirements ensure patients can safely participate in the study. This trial is studying Squamous Cell Carcinoma Head and Neck Cancer (HNSCC), so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures overall survival, which means the study tracks how long patients live after starting treatment. The specific primary outcome measures are: Overall survival (From the date of randomization to the date of death from any cause up to 54 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to improve survival rates for patients with recurrent or metastatic head and neck cancer by comparing new treatments to standard care. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Squamous Cell Carcinoma Head and Neck Cancer (HNSCC), where improved treatment options are needed.

Investor Insight

The large market size and competitive landscape in head and neck cancer treatments suggest a high approval probability for this trial. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 780 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about your eligibility and the potential benefits and risks of participating in the study. You will receive infusions of the study drugs every 3 weeks until your cancer progresses or you experience side effects. The trial is being conducted at multiple sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 780 participants

Interventions

• DRUG: Ivonescimab 10 mg/kg — Ivonescimab is a humanized immunoglobulin (Ig) G1 monoclonal antibody (mAb) being investigated as a cancer immunotherapy agent. Ivonescimab binds to human VEGF-A which is involved in tumor angiogenesis, and to human PD-1 that is a cell surface receptor expressed primarily on activated T cells and acts to inhibit T cell activation.
• DRUG: Ligufalimab — AK117 is a humanized IgG4 mAb being investigated as a cancer immunotherapy agent
• DRUG: Pembrolizumab (KEYTRUDA ®) — Pembrolizumab is a humanized monoclonal antibody (IgG4 kappa isotype with stabilizing sequence alteration in the Fc region) against PD-1 (programmed cell death-1), produced in Chinese hamster ovary cells by recombinant DNA technology.

Primary Outcomes

• Overall survival (From the date of randomization to the date of death from any cause up to 54 months)

Full Eligibility Criteria

Inclusion Criteria:

1. Patient capable of voluntary giving her/his written informed consent.
2. Age ≥ 18 and \< 80 years old at the time of enrolment.
3. Eastern Cooperative Oncology Organization (ECOG) performance status score of 0 or 1.
4. Expected survival ≥ 6 months at randomization.
5. Patient is histologically and/or cytologically confirmed to have r/m HNSCC (according to the International Union Against Cancer and the American Joint Committee on Cancer 8th edition staging system) with a primary tumour initially or currently located in the oral cavity, oropharynx, hypopharynx, or larynx.
6. HPV status test results based on tumour tissue samples must be obtained prior to randomization for patients with oropharyngeal cancer.
7. No prior systemic anti-tumour therapy for R/M HNSCC. Note: Patients who have previously received adjuvant/neoadjuvant chemotherapy with curative intent for non-metastatic disease, radiotherapy, or radical radiotherapy in combination with chemotherapy or cetuximab/EGFR based therapy for locally advanced disease are eligible for this study if disease progression occurs \> 6 months after the end of the last treatment.
8. At least one measurable lesion according to RECIST v1.1, or measurable lesion with clear radiographic progression after local therapy, and the lesion must be suitable for repeated accurate measurements (see Appendix 3).
9. Tumours must be PD-L1 positive (CPS ≥ 1) as confirmed by CE-IVD immunohistochemistry assay based on local assessment with any assay validated for HNSCC in a laboratory compliant with National provisions. The measurement of PD-L1 protein expression can be performed based on archival tissue sample before the diagnosis of R/M tumour or based on tissue sample obtained after the diagnosis of a R/M tumour.
10. Good organ function is determined by the following requirements:

    a.Haematology (satisfactory laboratory test results obtained during the screening period, and no blood components used within 14 days of cell growth factor supportive therapy): i.Absolute neutrophil value (ANC) ≥ 1.5×109/L (1,500/mm3) ii.Platelet count ≥ 100×109/L (100,000/mm3) iii.Haemoglobin ≥ 10 g/dL b.Kidneys: i.Calculated creatinine clearance (Appendix 4) ≥ 50 mL/min ii.Urine protein ≤ 2+ or 24 hours (h) urine protein quantification \< 1.0 g c.Liver: i.Serum total bilirubin ≤ 1.5× upper limit of normal (ULN); for patients with liver metastases or confirmed/suspected Gilbert syndrome, ≤ 3 × ULN ii.AST and ALT ≤ 2.5×ULN; For patients with liver metastases, AST and ALT ≤ 5×ULN iii.Serum albumin ≥ 28 g/L d.Coagulation function: International normalized ratio (INR) and/or activated partial thromboplastin time (APTT) ≤ 1.5× ULN. This applies only to patients who are not on therapeutic anti- coagulation. Patients receiving therapeutic anti-coagulation should be on a stable dose.

Exclusion Criteria:

1. Primary tumour site (any histology) of nasopharynx, nasal cavity, sinuses, salivary glands, thyroid or parathyroid glands, skin, or unknown primary site of tissue origin.
2. Patient with malignancies other than HNSCC within 3 years prior to enrolment. Patients with other tumours that have been cured through local treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ, are not excluded.
3. Concurrent enrolment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study; Received study treatment within 4 weeks prior to randomization.
4. Prior treatment with systemic anti-angiogenic drugs.
5. Previous head and neck re-irradiation for recurrent/metastatic disease
6. Prior immunotherapy, including immune checkpoint inhibitors (e.g., anti-PD-1/L1 antibody, anti- CTLA-4 antibody, anti-TIGIT antibody, anti-LAG3 antibody, anti-CD47, anti-SIRPα, etc.), immune checkpoint agonists (e.g., ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy, and any other treatment that targets tumour immunity including therapeutic tumour vaccine, and other adjuvant/neoadjuvant anti-PD-1 based therapy.
7. Patients with ulcers on the skin surface related to the current cancer during the screening period, superficial or protruding skin lesions with excessive surface tension and a greater risk of ulceration, or other patients with a greater risk of ulceration as assessed by the investigator. Patients with recent tracheostomy involving the tumour which are at risk of bleeding.
8. Imaging during the screening period shows that the tumour invades/infiltrates the surrounding important organs (such as trachea, oesophagus, and based on investigator assessment ofbleeding risk) and/or large blood vessels in the neck (such as subclavian artery, common internal and/or external carotid artery, etc.) or if the investigator judges that entering the study might cause a potential risk of bleeding.
9. Presence of brainstem, meningeal metastases, spinal cord metas

Frequently Asked Questions

Related Conditions

• Related conditions include other types of head and neck cancer, lung cancer, and other forms of squamous cell carcinoma.
• Therapeutic areas include oncology, immunotherapy, and cancer treatment.

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