Amivantamab Combinations for Head and Neck Cancer

(OrigAMI-4 Trial)

Recruiting at 68 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Janssen Research & Development, LLC

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2 years and 2 months

287 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of amivantamab (Rybrevant), both alone and combined with other drugs, for treating head and neck cancer that has recurred or spread. The trial includes different treatment groups, with some participants receiving amivantamab with pembrolizumab (an immunotherapy), paclitaxel (a chemotherapy drug), or carboplatin (another chemotherapy drug). It seeks participants with head and neck cancer affecting daily life, particularly those with tumors in the mouth, throat, or voice box. Participants must have confirmed cancer that cannot be cured with local treatments and should know specific details about their cancer, such as HPV status. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that amivantamab is generally well-tolerated. In one study, 18.2% of patients experienced infusion-related reactions (IRRs), but these were mild, only reaching grade 1 or 2 in severity. This indicates that side effects are usually manageable.

For combination treatments, amivantamab with paclitaxel has demonstrated promising safety results. Although specific details on side effects remain limited, the combination is under active study for its potential benefits, suggesting a reasonable safety profile at this stage of testing.

When combined with pembrolizumab, amivantamab has been studied for its ability to help the immune system fight cancer cells more effectively. While detailed safety data is not provided, ongoing research indicates confidence in its safety for continued trials.

The combination of amivantamab, pembrolizumab, and carboplatin is also under investigation. This combination builds on the known safety of each drug, which previous studies have found to be tolerable.

Since this trial is in the early stages (Phase 1/2), the main goal is to assess safety and determine the best doses. Some risks are still being evaluated, but the treatment has shown enough promise to continue testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Amivantamab for head and neck cancer because it offers a fresh approach compared to traditional treatments like surgery, radiation, and chemotherapy. Amivantamab is a monoclonal antibody that targets specific proteins on cancer cells, potentially leading to more precise and effective results with fewer side effects. It works differently from existing therapies by directly interfering with the growth signals of cancer cells. Additionally, Amivantamab can be used in combination with other drugs like pembrolizumab and carboplatin, which might enhance its effectiveness and provide a more robust treatment option for patients. This targeted action and potential for combination therapy make Amivantamab a promising candidate in the fight against head and neck cancer.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that using amivantamab alone achieves a 45% success rate in shrinking tumors for patients with recurring or spreading head and neck cancer. In 82% of these patients, the tumors reduced quickly and remained smaller. In this trial, some participants will receive amivantamab alone, while others will receive it in combination with other drugs. One treatment arm combines amivantamab with paclitaxel, which continues to yield good results. Another arm combines amivantamab with pembrolizumab, enhancing its cancer-fighting ability. Additionally, a treatment arm includes amivantamab, pembrolizumab, and carboplatin, which might further increase effectiveness based on the individual performance of these drugs. These combinations are being studied to determine the best treatment for head and neck cancer patients. ^{1 4 6 7 8}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Amivantamab
• Paclitaxel
• Pembrolizumab

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.

How Is the Trial Designed?

Group I: Cohort 6: Amivantamab + Pembrolizumab 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, along with intravenous injection of pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle) (Neoadjuvant Phase). In the adjuvant phase, pembrolizumab IV (200 mg) will be administered q3w from Adjuvant Cycle 1 Day 1 to Adjuvant Cycle 15 Day 1 and amivantamab SC 2,400 mg (3,360 mg for \>80 kg) will be administered q3w from Adjuvant Cycle 4 Day 1 to Adjuvant Cycle 15 Day 1.

Group II: 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 III: 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 IV: 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 V: 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 VI: 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 (IV) injection of pembrolizumab 200 mg q3w (on Day 1 of each 21-day cycle).

Group VII: 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.

Amivantamab is already approved in United States, European Union for the following indications:

Approved in United States as Rybrevant for:

• Locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Approved in European Union as Rybrevant for:

• Locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations
• Locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

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 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]

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]

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]

In a study involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

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. Tao, Y., Biau, J., Sun, XS., et al.[2023]

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]

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]

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]

Citations

1. jnj.com jnj.com/media-center/press-releases/subcutaneous-amivantamab-delivers-promising-45-percent-overall-response-rate-with-median-duration-of-7-2-months-in-recurrent-or-metastatic-head-and-neck-cancer

Subcutaneous amivantamab delivers promising 45 percent ... Responses were rapid and durable, and tumor shrinkage was observed in 82 percent of patients New findings from this investigational study ...

2. prnewswire.com prnewswire.com/news-releases/subcutaneous-amivantamab-delivers-promising-45-percent-overall-response-rate-with-median-duration-of-7-2-months-in-recurrent-or-metastatic-head-and-neck-cancer-302588232.html

Subcutaneous amivantamab delivers promising 45 percent ... Responses were rapid and durable, and tumor shrinkage was observed in 82 percent of patients. New findings from this investigational study ...

3. pharmacytimes.com pharmacytimes.com/view/amivantamab-shows-45-response-rate-in-pretreated-head-and-neck-cancer-origami-4-findings

Amivantamab Shows 45% Response Rate in Pretreated ... Subcutaneous amivantamab demonstrated robust activity in patients with recurrent or metastatic head and neck squamous cell carcinoma ...

4. jnj.com jnj.com/innovativemedicine/emea/media-center/press-releases/subcutaneous-rybrevant-amivantamab-delivers-promising-45-percent-overall-response-rate-with-median-duration-of-response-of-7-2-months-in-recurrent-or-metastatic-head-and-neck-cancer

Subcutaneous RYBREVANT®▼(amivantamab) delivers ... Responses were rapid and durable, and tumour shrinkage was observed in 82 percent of patients1 New findings from this investigational study ...

5. jnjmedicalconnect.com jnjmedicalconnect.com/products/rybrevant/medical-content/use-of-rybrevant-in-head-neck-cancer-origami4-study

Use of RYBREVANT in Head & Neck Cancer - OrigAMI-4 ... Efficacy outcomes for amivantamab SC monotherapy in cohort 1 are included in Table: Antitumor Activity in the Amivantamab SC Monotherapy Cohort ...

6. jnjmedicalconnect.com jnjmedicalconnect.com/products/rybrevant/medical-content/rybrevant-amivantamabvmjw

RYBREVANT® (amivantamab-vmjw) Overall, 6 (18.2%) patients reported infusion-related reactions (IRRs) with amivantamab SC, all of which were grade 1-2 in severity. Preliminary ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06385080

NCT06385080 | A Study of Amivantamab Alone or in ... The purpose of this study is to determine safety and preliminary efficacy of amivantamab monotherapy, amivantamab in addition to pembrolizumab, amivantamab ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11735833/

Real-World Efficacy and Safety of Amivantamab for EGFR ... In summary, this real-world analysis is the first to evaluate efficacy and safety of using amivantamab in different subclasses of patients with EGFR-mutant lung ...