AMG 355 + Pembrolizumab for Advanced Solid Tumors

Recruiting at 31 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Amgen

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Brain metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

535 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment for individuals with advanced solid tumors, such as certain lung, colon, stomach, and skin cancers. The researchers aim to determine if AMG 355, an experimental treatment, alone or combined with pembrolizumab (KEYTRUDA), is safe and what dose is most effective. Individuals whose cancers have returned or not responded to other treatments might qualify. Participants must be willing to undergo biopsies and have a life expectancy of more than three months. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take systemic corticosteroids or other immunosuppressive therapies within 7 days before starting the study treatment.

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

Research shows that AMG 355 is still under study to ensure its safety. As this is an early trial, limited safety information exists about AMG 355 alone or in combination with pembrolizumab. Early trials primarily assess treatment tolerance, so detailed safety results are still being gathered.

Pembrolizumab, however, is a more established drug already approved for other uses. It is generally well-tolerated, but like any medication, it can cause side effects. These may include tiredness, nausea, or changes in lab tests, varying from person to person.

In summary, while more is known about the safety of pembrolizumab, AMG 355 is new and undergoing safety testing. This trial is crucial to understanding how well people tolerate AMG 355 alone and in combination with pembrolizumab. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AMG 355 combined with pembrolizumab because it represents a novel approach for treating advanced solid tumors. Pembrolizumab is already well-known for its role in helping the immune system attack cancer cells, but AMG 355 introduces a new active ingredient that might boost this effect. Unlike standard treatments that primarily rely on a single method of action, this combination may enhance the immune response more effectively, potentially leading to better outcomes for patients. Additionally, AMG 355 as a monotherapy offers a fresh alternative for those who might not respond to current options, providing hope for more personalized cancer care.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that pembrolizumab helps treat various solid tumors, such as certain lung and stomach cancers, by improving survival rates. It is already used for these cancers. This trial tests AMG 355 as a new drug to determine its safety and effectiveness for solid tumors. Participants may receive AMG 355 alone or with pembrolizumab to evaluate if the combination improves treatment for advanced solid tumors. The ongoing trials aim to find the best dose and identify any side effects. ^{1 2 3 4 5}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced solid tumors, including specific types like NSCLC, CRC, GC, and melanoma. Participants should be relatively healthy (performance status 0 or 1), have a life expectancy of more than three months, and at least one measurable tumor lesion. A fresh biopsy before joining the study is preferred.

Inclusion Criteria

My cancer has returned or didn't respond to treatment, and I can't have standard therapies.

Life expectancy of > 3 months, in the opinion of the investigator

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I haven't taken high doses of steroids or immunosuppressants in the last week.

I haven't needed systemic treatment for an autoimmune disease in the last 2 years.

I stopped a cancer treatment due to side effects from immune therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AMG 355 as monotherapy or in combination with pembrolizumab to evaluate safety, tolerability, and determine dosing

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AMG 355
• Pembrolizumab

Trial Overview The trial tests AMG 355 alone and combined with Pembrolizumab to find safe dosages for people with advanced solid tumors. It aims to determine the safest highest dose possible (maximum tolerated dose) and an effective phase 2 dose.

How Is the Trial Designed?

Group I: Group B: AMG 355 and pembrolizumab Experimental Treatment 2 Interventions

Specified dose on specified days

Group II: Group A: AMG 355 monotherapy Experimental Treatment 1 Intervention

Specified dose on specified days

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

In a phase 3 trial involving 1177 participants with completely resected stage IB-IIIA non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved median disease-free survival to 53.6 months compared to 42.0 months for placebo, indicating its efficacy as an adjuvant therapy.

The safety profile of pembrolizumab was consistent with previous studies, showing no new safety signals, although serious adverse events were more common in the pembrolizumab group (24%) compared to placebo (15%), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. O'Brien, M., Paz-Ares, L., Marreaud, S., et al.[2022]

In a study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab and pemetrexed-carboplatin (PC) significantly improved the objective response rate (56.7% vs. 30.2% with PC alone) and progression-free survival (PFS) compared to PC alone, with a hazard ratio (HR) of 0.53.

The updated analysis showed a favorable overall survival (OS) hazard ratio of 0.56 for the pembrolizumab plus PC group, indicating a significant survival benefit, although 41% of patients experienced grade 3 to 5 treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. Borghaei, H., Langer, CJ., Gadgeel, S., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a meta-analysis of 11 clinical trials involving 3713 patients, the overall incidence of fatal adverse events (FAEs) associated with pembrolizumab was found to be 1.2%, indicating a relatively low risk of severe complications from this immune checkpoint inhibitor.

The incidence of FAEs varied significantly by tumor type, with breast cancer patients experiencing a higher risk (3.1%) compared to melanoma patients (0.2%), and the combination of pembrolizumab with chemotherapy resulted in a much higher incidence of FAEs (7.0%) compared to pembrolizumab alone (0.7%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal Adverse Events Associated with Pembrolizumab in Cancer Patients: A Meta-Analysis. Sher, AF., Golshani, GM., Wu, S.[2020]

Pembrolizumab (Keytruda) received FDA accelerated approval for treating recurrent gastric or gastroesophageal junction adenocarcinoma in patients whose tumors express PD-L1, based on a multicenter trial involving 259 patients, showing a 13.3% overall response rate.

The treatment was associated with common side effects like fatigue and decreased appetite, and serious adverse reactions included pneumonia and pulmonary embolism, highlighting the need for careful patient monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing PD-L1. Fashoyin-Aje, L., Donoghue, M., Chen, H., et al.[2021]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06131398

NCT06131398 | A Study of AMG 355 Alone and in ... The primary objectives of this study are to: Evaluate the safety and tolerability of AMG 355 as monotherapy and in combination with pembrolizumab in ...

2. dana-farber.org dana-farber.org/clinical-trials/24-331

A Phase 1 First-in-Human Study Evaluating the Safety, ... The primary objectives of this study are to: - Evaluate the safety and tolerability of AMG 355 as monotherapy and in combination with pembrolizumab in ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01718

A Study of AMG 355 Alone and in Combination With ... The primary objectives of this study are to: - Evaluate the safety and tolerability of AMG 355 as monotherapy and in combination with pembrolizumab in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06131398?term=NCT06131398&rank=1

A Study of AMG 355 Alone and in Combination With ... The primary objectives of this study are to: Evaluate the safety and tolerability of AMG 355 as monotherapy and in combination with pembrolizumab in ...

5. humanforschung-schweiz.ch humanforschung-schweiz.ch/en/trial-search/study-detail/65769/translate/en/?cHash=bacb3395c8a4d53d62c34aae8a561646

A study to evaluate a new drug called AMG 355, ... The study involves the treatment of patients with advanced solid tumors, including non-small cell lung cancer, colorectal cancer, gastric cancer ...