AMG 355 + Pembrolizumab for Advanced Solid Tumors

Recruiting at 26 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

Trial Summary

What is the purpose of this trial?

The primary objectives of this study are to: * Evaluate the safety and tolerability of AMG 355 as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors * Determine the recommended phase 2 dose and the maximum tolerated dose for AMG 355 as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors.

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.

What data supports the effectiveness of the drug pembrolizumab for advanced solid tumors?

Pembrolizumab has shown effectiveness in treating various solid tumors, including non-small cell lung cancer and gastric cancer, by improving survival rates and response durations. It works by helping the immune system attack cancer cells, and has been approved for use in certain cancers based on these positive outcomes. ^{1 2 3 4 5}

Is the combination of AMG 355 and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, and nausea. Serious side effects, though rare, include lung inflammation (pneumonitis) and heart problems. The risk of fatal adverse events is similar to chemotherapy, and these risks can vary depending on the type of cancer and whether it's combined with other treatments. ^{1 2 6 7 8}

What makes the drug combination of AMG 355 and pembrolizumab unique for treating advanced solid tumors?

The combination of AMG 355 and pembrolizumab is unique because it pairs a novel investigational drug (AMG 355) with pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells. This combination aims to enhance the immune response against advanced solid tumors, potentially offering a new treatment option where standard therapies may not exist. ^{1 2 3 9 10}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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) 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 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 (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]

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]

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) 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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

4. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing PD-L1. [2021]

5. United States 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. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Fatal Adverse Events Associated with Pembrolizumab in Cancer Patients: A Meta-Analysis. [2020]

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

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

10. England 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. [2022]