Osimertinib + Carotuximab for Lung Cancer

Recruiting at 4 trial locations

Overseen By Clinical Trial Recruitment Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Karen Reckamp, MD, MS

Must be taking: Osimertinib

Must not be taking: Thrombolytics

Disqualifiers: Interstitial lung disease, Hypertension, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine the combination of osimertinib and carotuximab to assess the safety and find the recommended dose for treatment of advanced EGFR-mutated non-small cell lung cancer (NSCLC). Safety and tolerability will be measured by the number of dose-limiting toxicities, according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 5, to find the maximum tolerated dose. The secondary objectives include evaluating the rate of objective response rate, duration of response, progression-free survival, and disease control rate, along with assessing biomarkers through tumor tissue and circulating tumor DNA.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients must have completed prior chemotherapy at least 3 weeks before starting the study drugs, and any adverse events from previous treatments must be resolved to a certain level. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Osimertinib and Carotuximab for lung cancer?

Osimertinib has shown significant effectiveness in improving disease-free survival in patients with certain types of lung cancer, specifically those with EGFR mutations, as seen in the ADAURA trial. It has also demonstrated excellent activity and less toxicity compared to other treatments for EGFR-mutated non-small cell lung cancer. ^{1 2 3 4 5}

What is known about the safety of Osimertinib for lung cancer treatment?

Osimertinib, used for certain types of lung cancer, has common side effects like diarrhea, rash, dry skin, and nail issues. Serious side effects occurred in 28% of patients, and 5.6% stopped treatment due to these effects. ^{5 6 7 8 9}

How is the drug combination of Osimertinib and Carotuximab unique for treating lung cancer?

The combination of Osimertinib and Carotuximab is unique because Osimertinib is a third-generation drug that targets specific mutations in lung cancer cells, potentially offering more effective treatment with fewer side effects compared to older drugs. This combination may enhance the effectiveness of treatment by targeting cancer cells in different ways. ^{3 10 11 12 13}

Research Team

Karen Reckamp, MD

Principal Investigator

Cedars-Sinai Medical Center

Eligibility Criteria

This trial is for adults with advanced non-squamous NSCLC that has specific EGFR mutations. Participants must have measurable disease, may have brain metastases if stable and asymptomatic, and should not have had recent major surgery or other cancer treatments. They need to agree to use contraception and be able to follow study requirements.

Inclusion Criteria

I can provide tissue from a recent biopsy after my cancer progressed on EGFR treatment.

My organs are working well.

I can take care of myself and am up and about more than half of the day.

Exclusion Criteria

I have had a heart attack or other major heart problem in the last 6 months.

You are allergic to Chinese hamster ovary products or other similar types of antibodies.

I have never been treated with carotuximab or any CD105 targeted antibody.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive osimertinib and carotuximab to assess safety and determine the recommended dose

4 weeks

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

Extension

Participants may continue to be monitored for progression-free survival and other outcomes

up to 2 years

Treatment Details

Interventions

• Carotuximab
• Osimertinib

Trial Overview The study tests the combination of osimertinib with carotuximab in patients with EGFR-mutated NSCLC. It aims to determine the safest dose by monitoring adverse reactions, while also looking at how well tumors respond, how long they stop growing, survival without disease progression, and overall disease control.

Participant Groups

Group I: Osimertinib with Carotuximab Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Karen Reckamp, MD, MS

Lead Sponsor

Trials

1

Recruited

60+

Enviro Therapeutics, Inc.

Collaborator

Trials

2

Recruited

160+

Findings from Research

A second patient with EGFR and MET-driven lung cancer showed a complete and durable response in the brain after treatment with the combination of capmatinib and osimertinib.

This suggests that combining capmatinib with osimertinib may be an effective salvage therapy for patients with EGFR-mutant lung cancer who have developed MET amplification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial Activity of Osimertinib Plus Capmatinib in a Patient With EGFR and MET-Driven Lung Cancer: Case Report. Gautschi, O., Diebold, J.[2021]

In the ADAURA study, adjuvant osimertinib significantly improved disease-free survival in patients with resected stage IB to IIIA EGFR-mutated non-small cell lung cancer (NSCLC) compared to placebo, with a median treatment duration of 35.8 months for osimertinib versus 25.1 months for placebo.

After three years of treatment, osimertinib showed no new safety concerns, and patients maintained their health-related quality of life, indicating that osimertinib is both effective and tolerable for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-Year Safety, Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial. John, T., Grohé, C., Goldman, JW., et al.[2023]

Osimertinib, an irreversible tyrosine kinase inhibitor, showed excellent activity in treating a 69-year-old man with metastatic EGFR-mutated non-small cell lung cancer, leading to a rapid treatment response despite initial severe pancytopenia.

After experiencing pancytopenia, the patient's dose of osimertinib was reduced from 80 mg to 40 mg daily, which allowed for continued effective treatment without further adverse events, demonstrating the potential for safe dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. Di Marino, P., Chiapperino, C., Primavera, FC., et al.[2022]

Osimertinib is an oral medication specifically designed to target the EGFR T790M mutation in advanced non-small cell lung cancer (NSCLC), which helps overcome resistance to previous EGFR TKI therapies.

It received accelerated approval in the USA in November 2015 for patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed after EGFR TKI treatment, and is currently undergoing further development for broader treatment applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. Greig, SL.[2022]

Osimertinib (Tagrisso) is a targeted therapy approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have the EGFR T790M mutation and have progressed after previous treatments.

The drug received special designations from the FDA, including breakthrough therapy and priority review, highlighting its significance in treating resistant forms of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Skoulidis, F., Papadimitrakopoulou, VA.[2022]

Osimertinib (TAGRISSO) received accelerated FDA approval for treating metastatic non-small cell lung cancer with the EGFR T790M mutation, showing significant tumor response rates of 57% and 61% in two major trials involving 411 patients.

While osimertinib demonstrated promising efficacy, common side effects included diarrhea (42%) and rash (41%), with 28% of patients experiencing severe adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Khozin, S., Weinstock, C., Blumenthal, GM., et al.[2022]

Osimertinib (Tagrisso) is an approved adjuvant treatment for non-small cell lung cancer patients with specific tumor mutations, highlighting its targeted therapeutic approach.

Common side effects of osimertinib include blood-related issues like leukopenia and thrombocytopenia, as well as gastrointestinal and skin reactions, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. Aschenbrenner, DS.[2023]

Osimertinib significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., et al.[2022]

In a study involving six patients with EGFR-mutated lung adenocarcinoma, the combination of osimertinib and ramucirumab was found to be generally safe, with only one case of dose-limiting toxicity (grade 3 appetite loss) and no other severe adverse events reported.

Five out of six patients showed a partial response to the treatment, with a median progression-free survival of 9.2 months for those with the EGFR T790M mutation, suggesting promising efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. Akamatsu, H., Ozawa, Y., Oyanagi, J., et al.[2023]

In a retrospective analysis of 32 patients with EGFR T790M-mutant non-small-cell lung cancer, osimertinib showed a 50% objective response rate and a median progression-free survival of 11.3 months, indicating its efficacy in clinical practice.

The median overall survival was 18.3 months, with better outcomes observed in patients without cerebral metastases and those with better performance status, highlighting the importance of these factors in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. Knetki-Wróblewska, M., Kowalski, DM., Czyżewicz, G., et al.[2022]

Osimertinib significantly improves disease-free survival (DFS) in adults with completely resected, early-stage EGFR mutation-positive non-small cell lung cancer (NSCLC), as shown in the pivotal ADAURA trial, regardless of prior adjuvant chemotherapy.

The treatment is well tolerated with a manageable safety profile, and it does not negatively impact health-related quality of life, making it a suitable option for adjuvant therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. Frampton, JE.[2022]

In a study of 62 patients with EGFR-mutated advanced non-small cell lung cancer, the combination of osimertinib and chemotherapy did not significantly improve progression-free survival compared to osimertinib alone, with median PFS of 15.8 months for monotherapy versus 14.6 months for the combination.

The overall response rate was higher in the osimertinib monotherapy group (71.4%) compared to the combination group (53.6%), and the safety profile of the combination treatment was comparable to previously reported data for carboplatin and pemetrexed, indicating it was generally tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib versus osimertinib plus chemotherapy for non-small cell lung cancer with EGFR (T790M)-associated resistance to initial EGFR inhibitor treatment: An open-label, randomised phase 2 clinical trial. Tanaka, K., Asahina, H., Kishimoto, J., et al.[2022]

The combination of osimertinib with selumetinib or savolitinib showed a promising objective response rate of around 42-44% in patients with advanced EGFR-mutant non-small-cell lung cancer, indicating potential efficacy of these combinations.

However, combining osimertinib with durvalumab was not feasible due to a higher incidence of interstitial lung disease, highlighting safety concerns with this particular combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer. Oxnard, GR., Yang, JC., Yu, H., et al.[2022]

References

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

Intracranial Activity of Osimertinib Plus Capmatinib in a Patient With EGFR and MET-Driven Lung Cancer: Case Report. [2021]

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

Three-Year Safety, Tolerability, and Health-Related Quality of Life Outcomes of Adjuvant Osimertinib in Patients With Resected Stage IB to IIIA EGFR-Mutated NSCLC: Updated Analysis From the Phase 3 ADAURA Trial. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Pancytopenia During Osimertinib Treatment in a Patient with EGFR-Mutated Non-Small Cell Lung Cancer. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. [2022]

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

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]

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

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]

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

New Adjuvant Drug for Lung Cancer. [2023]

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

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. [2022]

11. France pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Osimertinib versus osimertinib plus chemotherapy for non-small cell lung cancer with EGFR (T790M)-associated resistance to initial EGFR inhibitor treatment: An open-label, randomised phase 2 clinical trial. [2022]

13. England pubmed.ncbi.nlm.nih.gov

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer. [2022]