Amivantamab Clinical Trials

What Is Amivantamab?

Amivantamab is a drug currently being investigated in clinical trials for the treatment of various cancers. It is often studied as a subcutaneous (SC) injection, sometimes in combination with other oral medications like lazertinib or with chemotherapy agents such as carboplatin and paclitaxel. Research indicates its use in treating cancers with specific genetic mutations, such as epidermal growth factor receptor (EGFR) mutations, particularly in Non-Small Cell Lung Cancer (NSCLC).

Amivantamab is currently being evaluated in 43 clinical trials, with a total enrollment of 10,495 participants. These trials began as early as 2015-11-20, with the latest projected to conclude in 2026. Among these, 19 trials are actively recruiting new participants, while 1 trial has been completed. The primary focus of these studies is to assess the safety and effectiveness of amivantamab, both alone and in combination with other treatments, for various advanced cancers.

Uses and Conditions Under Study

Amivantamab is primarily under investigation for the treatment of various cancers. The majority of studies focus on specific types of lung cancer and other solid tumors.

• Non-Small Cell Lung Cancer (NSCLC): This is the most extensively studied condition for amivantamab. NSCLC is a common type of lung cancer, and amivantamab is being investigated for its potential to target specific epidermal growth factor receptor (EGFR) mutations, including EGFR exon 20 insertion mutations, which can drive cancer growth. Amivantamab is being studied in a total of 18 trials for various forms of NSCLC.
• Colorectal Cancer: Amivantamab is also being explored for its potential in treating cancers of the colon and rectum. These studies aim to understand how the drug might interfere with cancer cell growth in colorectal neoplasms. There are 4 trials investigating amivantamab for colorectal cancer.
• Squamous Cell Carcinoma of Head and Neck: This type of cancer affects the head and neck region. Amivantamab's potential to target specific pathways involved in cancer development is being evaluated in 2 trials for this condition.
• Other Cancers: Amivantamab is also being studied in individual trials for other challenging cancers. These include Diffuse Hemispheric Glioma, H3 G34-Mutant, a type of brain tumor, and Esophageal Neoplasms, which are cancers affecting the esophagus.

Dosing

Amivantamab has been studied in various dosage forms and schedules in clinical trials. It is primarily administered as a subcutaneous (SC) injection, but intravenous (IV) infusion has also been investigated.

Specific dosing regimens vary depending on the trial and the combination therapy used:

• One regimen involves subcutaneous amivantamab at a dose of 1600 mg (or 2240 mg for participants weighing 80 kg or more) administered weekly (QW) up to Cycle 2 Day 1, and then every two weeks (Q2W) thereafter. This schedule has been studied in combination with lazertinib.
• Another investigational regimen for subcutaneous amivantamab includes an initial dose of 1600 mg (or 2240 mg for participants ≥80 kg) on Cycle 1 Day 1. This is followed by doses of 2400 mg (or 3360 mg for participants ≥80 kg) on Cycle 1 Day 8 and Day 15, and then every three weeks (Q3W) starting from Cycle 2 Day 1. This schedule has been studied in combination with monochemotherapy.

These dosages are part of ongoing research to determine the most effective and safest treatment protocols for different cancer types and patient populations. No specific pediatric doses are detailed in the provided trial data; dosages are often adjusted based on body weight for adult participants.

Side Effects

In a clinical trial involving 421 patients taking Amivantamab, the most common side effect was paronychia (inflammation or infection around the fingernails or toenails), affecting 68.4% of patients. This was significantly higher than the 28.4% of patients who experienced paronychia on placebo.

Other frequently reported side effects with Amivantamab, compared to placebo, included:

• Infusion-related reactions: 62.0% of patients on Amivantamab experienced these, while no patients on placebo did (0.0%).
• Rash: Occurred in 61.8% of patients taking Amivantamab, compared to 35.3% on placebo.
• Hypoalbuminaemia (low albumin levels in the blood): Seen in 48.5% of Amivantamab patients versus 6.7% on placebo.
• Oedema peripheral (swelling, typically in the legs or ankles): Affected 35.6% of patients on Amivantamab, compared to 7.5% on placebo.
• Increased alanine aminotransferase (a liver enzyme): Reported in 36.1% of patients taking Amivantamab, versus 15.9% on placebo.
• Constipation: Experienced by 29.0% of Amivantamab patients, compared to 14.2% on placebo.
• Dermatitis acneiform (acne-like skin inflammation): Occurred in 29.0% of patients on Amivantamab, versus 15.6% on placebo.

Conversely, diarrhea was reported less often in patients taking Amivantamab (29.2%) compared to those on placebo (40.1%).

Clinical Trial Results

Amivantamab in Non-Small Cell Lung Cancer (NSCLC)

In a study (NCT04487080) comparing Amivantamab and lazertinib combination therapy to osimertinib in locally advanced or metastatic NSCLC, patients receiving Amivantamab plus lazertinib had a median progression-free survival (PFS) of 23.72 months. This was longer than patients treated with osimertinib alone (16.59 months) or lazertinib alone (18.46 months).

Another study (NCT04538664) focused on advanced or metastatic NSCLC with specific epidermal growth factor receptor (EGFR) exon 20 insertions. Patients who received Amivantamab combined with chemotherapy experienced a median PFS of 11.37 months. This was a significant improvement compared to patients who received chemotherapy alone, who had a median PFS of 6.70 months.

A further trial (NCT04988295) investigated Amivantamab and lazertinib with platinum-based chemotherapy in EGFR-mutated NSCLC after osimertinib failure. The combination of lazertinib, Amivantamab, and chemotherapy led to a median PFS of 8.31 months. This was more than double the median PFS of 4.17 months seen in patients treated with chemotherapy alone. Patients receiving Amivantamab plus chemotherapy also showed an improved median PFS of 6.28 months compared to chemotherapy alone.

Amivantamab in Gastric or Esophageal Cancer

A Phase 2a study (NCT04945733) evaluated Amivantamab in previously treated advanced or metastatic gastric or esophageal cancer. For patients with esophageal cancer receiving the 1050/1400 mg dose, the disease control rate (DCR) was 67.9%, meaning their cancer either shrank or remained stable. The median progression-free survival (PFS) in this group was 4.11 months, with a median duration of response (DOR) of 2.86 months. For patients with gastric cancer at the same dose, the DCR was 26.1%, and the median PFS was 1.45 months.

Subcutaneous vs. Intravenous Amivantamab

A study (NCT05388669) compared subcutaneous (SC) Amivantamab with intravenous (IV) Amivantamab, both in combination with lazertinib, for EGFR-mutated advanced or metastatic NSCLC. The study found that the overall drug exposure (measured by area under the curve, AUC) was similar between the two administration methods. For example, the geometric mean AUC for SC Amivantamab was 135861 micrograms*hour per milliliter, compared to 131704 micrograms*hour per milliliter for IV Amivantamab. Notably, subcutaneous administration resulted in higher average trough concentrations of Amivantamab at steady state, with a geometric mean of 206 micrograms per milliliter for SC compared to 144 micrograms per milliliter for IV in one region, and 335 mcg/mL for SC compared to 293 mcg/mL for IV in another region.

Currently Recruiting Trials

Amivantamab is currently being investigated in a variety of clinical trials for different types of cancer. These studies aim to understand its effectiveness and safety, often in combination with other treatments. If you or a loved one are considering participating, here's a look at some of the trials actively seeking participants:

• For people with head and neck cancer that has returned or spread, the SWOG Cancer Research Network is conducting a NCT07062354 Phase 2 study. It combines amivantamab with carboplatin and paclitaxel, targeting an enrollment of 50 participants.
• Another Phase 2 trial, NCT07042295, sponsored by the National Cancer Institute (NCI), is comparing amivantamab and hyaluronidase to cetuximab for advanced skin squamous cell carcinoma in people with weakened immune systems, with a target enrollment of 86 individuals.
• Janssen Research & Development, LLC is sponsoring a Phase 1/2 study, NCT07227025, exploring amivantamab and olomorasib combination therapy for metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C mutation, aiming for 60 participants.
• A large Phase 3 study, NCT07276399, also by Janssen, is comparing amivantamab plus standard of care (pembrolizumab and carboplatin) to standard of care alone for recurrent/metastatic head and neck cancer, with an enrollment goal of 500 participants.
• Fondazione Ricerca Traslazionale is running a Phase 2 trial, NCT07392658, for NSCLC patients with EGFR exon20 insertion mutations who are unfit for platinum-based chemotherapy, seeking 33 participants.
• ORIC Pharmaceuticals is investigating ORIC-114 in combination with subcutaneous amivantamab for EGFR Exon20 insertion mutant NSCLC in a Phase 1 study, NCT06816992, with an enrollment target of 76 patients.
• Janssen has a Phase 2 study, NCT06667076, looking at amivantamab with lazertinib or with platinum-based chemotherapy for common EGFR-mutated locally advanced or metastatic NSCLC, aiming for 480 participants.
• For colorectal cancer, Janssen is sponsoring a Phase 3 trial, NCT06750094, comparing amivantamab and FOLFIRI to cetuximab/bevacizumab and FOLFIRI in patients with KRAS/NRAS and BRAF wild-type disease who have received prior chemotherapy, with a goal of 700 participants.
• SWOG Cancer Research Network is conducting an Expanded Lung-MAP Phase 2 trial, NCT06116682, for advanced NSCLC with increased copies of the MET gene, planning to enroll 88 patients.
• The University Hospital, Essen, is running a Phase 2 study, NCT06784791, on preoperative amivantamab alone or with carboplatin/pemetrexed for resectable NSCLC with oncogenic EGFR mutations, targeting 20 participants.
• Janssen has another Phase 3 colorectal cancer study, NCT06662786, comparing amivantamab and mFOLFOX6 or FOLFIRI to cetuximab and mFOLFOX6 or FOLFIRI as first-line treatment for unresectable or metastatic left-sided KRAS/NRAS and BRAF wild-type disease, with a substantial enrollment target of 1000 participants.
• The Institute of Cancer Research, United Kingdom, is conducting a Phase 1 study, NCT06632236, called 5G-EMERALD, to evaluate amivantamab in malignant brain tumors, with 12 participants.
• Kumquat Biosciences Inc. is sponsoring a Phase 1 trial, NCT06507306, to investigate KQB198 as monotherapy and in combination with amivantamab for advanced solid malignancies, aiming for 100 participants.
• Janssen is also investigating amivantamab alone or with other agents in a Phase 1/2 study, NCT06385080, for head and neck cancer, with an enrollment target of 287 participants.
• A Phase 2 study by Janssen, NCT06120140, is evaluating enhanced dermatological care to reduce rash and paronychia in EGFR-mutated NSCLC treated with amivantamab plus lazertinib, seeking 300 participants.
• The Gruppo Oncologico del Nord-Ovest is running a Phase 2 "UNICORN" trial, NCT05845450, for pre-operative targeted treatments in molecularly selected resectable colorectal cancer, with 197 participants.
• Janssen has a Phase 2 study, NCT05498428, investigating subcutaneous amivantamab in advanced or metastatic solid tumors, including EGFR-mutated NSCLC, with a large enrollment target of 520 participants.
• Another Phase 1/2 study by Janssen, NCT05379595, is assessing amivantamab monotherapy and in addition to standard-of-care chemotherapy for advanced or metastatic colorectal cancer, aiming for 225 participants.
• Finally, the Vall d'Hebron Institute of Oncology is conducting a modular multi-basket Phase 2 trial, NCT03767075, to improve personalized medicine in cancer patients, with amivantamab as one of the therapies being evaluated, targeting 1000 participants.

Where to Participate

Clinical trials for Amivantamab are widely accessible across the United States, with a broad geographic reach encompassing 519 sites in 330 cities across 46 states. This extensive network aims to make participation convenient for a diverse patient population.

The cities with the most active recruiting sites include:

• New York, New York (13 sites)
• Atlanta, Georgia (10 sites)
• Ann Arbor, Michigan (9 sites)
• Los Angeles, California (9 sites)
• Fairfax, Virginia (8 sites)
• Nashville, Tennessee (8 sites)
• Portland, Oregon (8 sites)
• Cleveland, Ohio (8 sites)
• Philadelphia, Pennsylvania (8 sites)
• St Louis, Missouri (8 sites)

Eligibility for these trials generally includes individuals aged 16 to 99 years, of all genders. Healthy volunteers are not eligible to participate, but children may be considered for some studies.

Development Timeline

The journey of Amivantamab in clinical development began on November 20, 2015, marking the start of its first clinical trial. Since then, the drug has been investigated in a total of 43 trials, collectively enrolling over 10,495 participants.

Janssen Research & Development, LLC has been the primary driving force behind Amivantamab's development, sponsoring 21 of these trials. Other institutions and pharmaceutical companies have also contributed to its research, including Memorial Sloan Kettering Cancer Center and the SWOG Cancer Research Network.

Initially, Amivantamab's development explored conditions such as IBS-C and hyperphosphatemia. However, its pipeline quickly expanded and focused on various cancers, demonstrating a significant shift in its therapeutic direction. The drug's development progressed through different phases, with 21 trials reaching Phase 2, 8 trials in Phase 1/2, and 7 trials advancing to Phase 3, indicating a mature and expanding research program. Its therapeutic scope now broadly includes a range of conditions such as Colorectal Neoplasms, Squamous Cell Carcinoma of Head and Neck, and various forms of Non-Small Cell Lung Cancer, particularly those with EGFR mutations. The development has also explored its potential in more rare and aggressive cancers like Malignant Primary Gliomas and Glioblastoma Multiforme, showcasing a comprehensive and evolving research strategy.