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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs, osimertinib and carotuximab (an experimental treatment), for individuals with advanced non-small cell lung cancer (NSCLC) that has specific mutations in the EGFR gene. The primary goal is to determine a safe dose and assess the treatment's effectiveness against the cancer. It suits those whose cancer has worsened despite previous treatments, including those who have used osimertinib for less than 12 weeks and have specific genetic markers in their blood. Participants should have progressed on prior cancer treatments but remain stable and symptom-free from untreated brain metastases. 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 combination therapy.

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.

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

Research is testing the safety of combining osimertinib and carotuximab to treat advanced lung cancer. Osimertinib is already used for some lung cancers, but it can sometimes cause heart-related side effects. Researchers are studying carotuximab to see if it can help when osimertinib stops working well.

This early-stage trial primarily aims to find the safest dose of these drugs. As the trial progresses, more information about safety will emerge. The trial will monitor for any serious side effects that might limit the dosage. Participants will contribute to understanding how well these drugs work together. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of Osimertinib and Carotuximab for lung cancer because it offers a fresh approach to treatment. Most existing treatments, like chemotherapy and targeted therapies, focus on inhibiting specific proteins that promote cancer growth. However, Carotuximab works differently by targeting the blood vessels that supply the tumor, potentially starving it of nutrients. When combined with Osimertinib, which targets specific mutations in cancer cells, this duo could offer a powerful one-two punch against lung cancer, potentially leading to more effective results than current treatments alone.

What evidence suggests that the combination of osimertinib and carotuximab could be effective for advanced EGFR-mutated non-small cell lung cancer?

Research shows that osimertinib often treats non-small cell lung cancer (NSCLC) with specific EGFR mutations. It generally works well and remains safe for patients. In this trial, participants will receive a combination of osimertinib and carotuximab. Carotuximab, when combined with osimertinib, might help when cancer stops responding to osimertinib alone. Studies suggest that carotuximab can block a protein called CD105, potentially enhancing osimertinib's effectiveness against resistant cancer cells. This combination is being tested to determine if it can improve treatment outcomes for people with advanced lung cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Karen Reckamp, MD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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 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]

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 (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 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]

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]

Citations

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The study of primary and acquired resistance to first-line ... Osimertinib is currently the common first-line therapy in EGFR-mutated non-small cell lung cancer patients. •. Understanding primary and acquired resistance ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39576954

A Systematic Review and Single-Arm Meta-Analysis Osimertinib demonstrated robust response in NSCLC harboring uncommon EGFR mutations, without unanticipated safety concerns.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20010

Postoperative radiotherapy and survival outcomes in pN2 ... Effect of carotuximab (ENV105)-mediated CD105 blockade on osimertinib sensitivity in EGFR-mutant non-small cell lung cancer persister cells.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6519771/

Cost‐Effectiveness of Osimertinib in Treating Newly ... Osimertinib as first‐line treatment yielded the greatest health outcomes but is not a cost‐effective strategy for lung cancer in the US and China.

5. biospace.com biospace.com/press-releases/kairos-pharma-ltd-announces-peer-reviewed-publication-highlighting-potentially-groundbreaking-discovery-in-overcoming-drug-resistance-in-non-small-cell-lung-cancer

Kairos Pharma Ltd. Announces Peer Reviewed Publication ... The study, titled, “CD105 blockade restores osimertinib sensitivity in drug-resistant EGFR-mutant non-small cell lung cancer,” demonstrated that ...

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Study of Osimertinib With Carotuximab in Advanced, EGFR ... 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 ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20009

Effect of carotuximab (ENV105)-mediated CD105 blockade ... Background: Osimertinib resistance in patients with EGFR-driven non-small cell lung cancer (NSCLC) contributes to mortality. Targeting bypass ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11900531/

Real-World Data on Osimertinib-Associated Cardiac Toxicity Lung cancer leads the global statistics for cancer-related deaths, surpassing the combined mortality rates of breast, prostate, colorectal, and ...

9. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05401110/study-of-osimertinib-with-carotuximab-in-advanced-egfr-mutated-non-small-cell-lung-cancer

Study of Osimertinib with Carotuximab in Advanced, EGFR- ... The purpose of this study is to examine the combination of osimertinib and carotuximab to assess the safety and find the recommended dose ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S1368764625000378

CD105 blockade restores osimertinib sensitivity in drug- ... Carotuximab effectively reduced the slow-cycling cell population and restored osimertinib sensitivity, offering a promising strategy for managing refractory ...