Amivantamab Combinations for Head and Neck Cancer

(OrigAMI-4 Trial)

Recruiting at 47 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Interstitial lung disease, Brain metastases, Cardiovascular disease, others

No Placebo Group

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called amivantamab alone and with two other drugs, pembrolizumab and paclitaxel. It targets patients with head and neck cancer that has come back or spread. Amivantamab blocks signals that help cancer grow, pembrolizumab helps the immune system fight cancer, and paclitaxel stops cancer cells from dividing. Pembrolizumab has shown benefits when used with chemotherapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any prior chemotherapy, targeted cancer therapy, immunotherapy, or investigational anticancer agents at least 2 weeks or 4 half-lives before starting the study treatment, with a maximum washout period of 28 days. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug combination including Amivantamab for head and neck cancer?

Pembrolizumab, one of the drugs in the combination, has shown potential benefits when used with radiotherapy for head and neck cancer, suggesting it might help the immune system fight the cancer more effectively. ^{1 2 3 4 5}

What makes the drug Amivantamab unique for head and neck cancer?

Amivantamab is unique because it is a bispecific antibody, meaning it can target two different proteins on cancer cells, which may enhance its ability to fight cancer compared to treatments that target only one protein. ^{1 6 7 8 9}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for people with recurrent or metastatic head and neck cancer, including squamous cell carcinoma. Participants should have a type of cancer that has returned after treatment or spread to other parts of the body.

Inclusion Criteria

My organs and bone marrow are functioning well without recent medical help.

Participants in Cohorts 1, 2, and 3B must have measurable disease according to RECIST version 1.1

My oropharyngeal tumor is p16 negative.

Exclusion Criteria

I have brain metastases or spinal issues not treated by surgery or radiation.

I do not have any uncontrolled illnesses like lung scarring or inflammation.

I have not taken any cancer treatments or experimental drugs recently.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive amivantamab monotherapy or in combination with other agents such as pembrolizumab, paclitaxel, and carboplatin

2 years and 2 months

Every 3 weeks (q3w) for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years and 2 months

Treatment Details

Interventions

• Amivantamab (Monoclonal Antibodies)
• Paclitaxel (Anti-metabolites)
• Pembrolizumab (Monoclonal Antibodies)

Trial Overview The study tests amivantamab alone, combined with pembrolizumab, and in combination with paclitaxel. It aims to find out how safe these treatments are and how well they work against advanced head and neck cancer.

Participant Groups

Group I: Cohort 5: Pembrolizumab + Amivantamab + Carboplatin (Dose Expansion) Experimental Treatment 3 Interventions

Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight \>=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight \>=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards in addition to intravenous injection of pembrolizumab 200 mg on Day 1 of each cycle, and carboplatin (area under the concentration-time curve \[AUC\] 5 milligram per milliliter \[mg/ml\]\*min) q3w on Day 1 of Cycles 1-6.

Group II: Cohort 4: Amivantamab Monotherapy Experimental Treatment 1 Intervention

Participants will receive subcutaneous injection of amivantamab monotherapy 1600 mg (2240 mg, if body weight \>=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight \>=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards.

Group III: Cohort 3B (Dose Expansion): Amivantamab + Paclitaxel Experimental Treatment 2 Interventions

Participants will receive subcutaneous injection of amivantamab at the determined RP2CD in addition to intravenous injection of paclitaxel 175 mg/m\^2 q3w (on Day 1 of each 21-day cycle) as confirmed by SET in Cohort 3A.

Group IV: Cohort 3A (Dose Confirmation): Amivantamab + Paclitaxel Experimental Treatment 2 Interventions

Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight \>=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight \>=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards, along with intravenous injection of paclitaxel 175 mg/m\^2 q3w (on Day 1 of each 21-day cycle) in dose confirmation Cohort 3A. The recommended Phase 2 combination dose (RP2CD) of amivantamab will be determined in conjunction with study evaluation team (SET) in this dose confirmation Cohort 3A.

Group V: Cohort 2: Amivantamab + Pembrolizumab (Dose Expansion Including Safety Run-in) Experimental Treatment 2 Interventions

Participants will receive subcutaneous injection of amivantamab 1600 mg (2240 mg, if body weight \>=80 kg) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight \>=80 kg) q1w for the remainder of Cycle 1 (Days 8 and 15), and q3w from Cycle 2 onwards, along with intravenous injection of pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle).

Group VI: Cohort 1: Amivantamab Monotherapy (Dose Expansion) Experimental Treatment 1 Intervention

Participants will receive subcutaneous injection of amivantamab monotherapy 1600 milligrams (mg) (2240 mg, if body weight \>=80 kilograms \[kg\]) on Cycle 1 Day 1 and 2400 mg (3360 mg, if body weight \>=80 kg) once every week (q1w) for the remainder of Cycle 1 (Days 8 and 15), and every 3 weeks (q3w) from Cycle 2 onwards.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

Duligotuzumab, when combined with chemotherapy, showed promising activity in treating recurrent/metastatic squamous cell cancer of the head and neck, with 67% of patients achieving objective responses, including complete and partial responses.

The combination therapy was associated with a higher frequency and severity of certain adverse events, such as neutropenia and anemia, compared to historical data, indicating that while effective, the treatment may increase the risk of chemotherapy-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib study of duligotuzumab (MEHD7945A) plus cisplatin/5-fluorouracil or carboplatin/paclitaxel for first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck. Jimeno, A., Machiels, JP., Wirth, L., et al.[2019]

In a phase II clinical trial involving 95 patients with recurrent and/or metastatic head and neck squamous cell carcinoma, the combination of cetuximab and nivolumab showed promising overall survival rates, with a median survival of 20.2 months for treatment-naive patients and 11.4 months for those previously treated.

The study found that higher levels of PD-L1 expression were linked to better response rates and longer overall survival, suggesting that biomarker assessment could help identify patients who may benefit most from this treatment combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Multi-institutional Clinical Trial Result of Concurrent Cetuximab and Nivolumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. Chung, CH., Li, J., Steuer, CE., et al.[2022]

Head and neck cancer cells can evade the immune system by developing tolerance in T cells and inhibiting T-cell pathways, which is a significant challenge in treating these cancers.

Recent advances in immuno-oncology, particularly the use of checkpoint inhibitors, show promise in improving treatment outcomes for recurrent and metastatic head and neck squamous cell carcinoma, with ongoing clinical trials focusing on their efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy and Checkpoint Inhibitors in Recurrent and Metastatic Head and Neck Cancer. Hashemi-Sadraei, N., Sikora, AG., Brizel, DM.[2020]

The study investigates the safety and efficacy of combining avelumab, an anti-PD-L1 monoclonal antibody, with cetuximab in patients with recurrent or metastatic squamous cell head and neck carcinoma, aiming to improve outcomes beyond the current standard of care.

Up to 16 participants will be enrolled in this phase II trial to assess the safety of the drug combination and determine the optimal dose of cetuximab, with secondary objectives focusing on tumor response and overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for the EACH trial: a multicentre phase II study evaluating the safety and antitumour activity of the combination of avelumab, an anti-PD-L1 agent, and cetuximab, as any line treatment for patients with recurrent/metastatic head and neck squamous cell cancer (HNSCC) in the UK. Ng, K., Metcalf, R., Sacco, J., et al.[2023]

The combination of avelumab, cetuximab, and radiotherapy was found to be tolerable for patients with locally advanced squamous-cell carcinoma of the head and neck, with an acceptable rate of severe adverse events (12% in experimental arms).

The trial included 82 patients and showed that most participants completed their planned radiotherapy, indicating that this new treatment approach is feasible and safe for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab-cetuximab-radiotherapy versus standards of care in locally advanced squamous-cell carcinoma of the head and neck: The safety phase of a randomised phase III trial GORTEC 2017-01 (REACH). Tao, Y., Aupérin, A., Sun, X., et al.[2021]

In a study of 256 Japanese patients with recurrent or metastatic head and neck cancer, nivolumab showed a median overall survival of 9.5 months and a median progression-free survival of 2.1 months over a follow-up period of 2 years, indicating its long-term effectiveness in real-world clinical practice.

The safety profile of nivolumab remained consistent, with immune-related adverse events occurring in 17.2% of patients, primarily involving endocrine and lung disorders, suggesting that it is a relatively safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of long-term nivolumab and subsequent chemotherapy in Japanese patients with head and neck cancer: 2-year follow-up from a multicenter real-world study. Yasumatsu, R., Shimizu, Y., Hanai, N., et al.[2022]

In a phase II study involving 55 patients with recurrent and/or metastatic head and neck squamous cell carcinoma, the combination of cetuximab and sorafenib did not show a significant clinical benefit, with an overall response rate of only 8% for both treatment arms.

Patients with p16-negative tumors or lower levels of the cytokine TGFβ1 experienced longer progression-free survival (PFS), suggesting that these factors may help identify individuals who could benefit more from cetuximab-based therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II efficacy and correlative studies of cetuximab with or without sorafenib in recurrent and/or metastatic head and neck squamous cell carcinoma. Gilbert, J., Schell, MJ., Zhao, X., et al.[2018]

In a phase Ib/III trial involving 36 patients with recurrent or metastatic head and neck squamous cell carcinoma, the combination of talimogene laherparepvec (T-VEC) and pembrolizumab showed a tolerable safety profile, with only one reported dose-limiting toxicity (fatal arterial hemorrhage) and no other treatment-related fatalities.

The combination therapy resulted in a confirmed partial response in 13.9% of patients, with median progression-free survival of 3.0 months and overall survival of 5.8 months, indicating that its efficacy was comparable to pembrolizumab alone based on historical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. Harrington, KJ., Kong, A., Mach, N., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase Ib study of duligotuzumab (MEHD7945A) plus cisplatin/5-fluorouracil or carboplatin/paclitaxel for first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II Multi-institutional Clinical Trial Result of Concurrent Cetuximab and Nivolumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy and Checkpoint Inhibitors in Recurrent and Metastatic Head and Neck Cancer. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Protocol for the EACH trial: a multicentre phase II study evaluating the safety and antitumour activity of the combination of avelumab, an anti-PD-L1 agent, and cetuximab, as any line treatment for patients with recurrent/metastatic head and neck squamous cell cancer (HNSCC) in the UK. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Avelumab-cetuximab-radiotherapy versus standards of care in locally advanced squamous-cell carcinoma of the head and neck: The safety phase of a randomised phase III trial GORTEC 2017-01 (REACH). [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

Outcomes of long-term nivolumab and subsequent chemotherapy in Japanese patients with head and neck cancer: 2-year follow-up from a multicenter real-world study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

A randomized phase II efficacy and correlative studies of cetuximab with or without sorafenib in recurrent and/or metastatic head and neck squamous cell carcinoma. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. [2021]