MGC018 for Small Cell Lung Cancer

(MGC018-SCLC Trial)

Recruiting at 3 trial locations

Overseen By Chul Kim

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Georgetown University

Must not be taking: Investigational agents

Disqualifiers: Leptomeningeal disease, Other malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: Approximately 1 year

17 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to test MGC018 in patients with relapsed or refractory Extensive-Stage Small-Cell Lung Cancer (ES-SCLC). The main question it aims to answer is: • Does the administration of MGC018 achieve a clinically meaningful response rate of 25% in patients with relapsed or refractory ES-SCLC? Participants enrolled in the trial will receive MGC018 through an intravenous (IV) infusion, every 28 days until disease progression or unacceptable toxicity. Tumor assessment will be done every 2 cycles (28 day cycles). Blood samples will be taken for biomarker analysis before treatment, on cycle 3 day 1, and at progression. A pretreatment biopsies will be done.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on other investigational agents, you cannot participate in this trial.

What data supports the effectiveness of the drug MGC018, Vobramitamab Duocarmazine, for treating small cell lung cancer?

While there is no direct data on MGC018, Vobramitamab Duocarmazine for small cell lung cancer, similar treatments like lorvotuzumab mertansine have shown promising results in targeting specific proteins on cancer cells, leading to significant tumor reduction in preclinical models. This suggests that targeted therapies can be effective against small cell lung cancer. ^{1 2 3 4 5}

What makes the drug MGC018 unique for treating small cell lung cancer?

MGC018, also known as Vobramitamab Duocarmazine, is unique because it is an antibody-drug conjugate, which means it combines an antibody with a drug to specifically target and kill cancer cells. This targeted approach is different from traditional chemotherapy, which affects both cancerous and healthy cells. ^{2 6 7 8 9}

Research Team

Chul Kim, MD

Principal Investigator

[e-mail]

Eligibility Criteria

This trial is for people with Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) that has come back or hasn't responded to treatment. Participants will receive MGC018 every 28 days via IV until their disease worsens or the side effects become too much.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

My small cell lung cancer is advanced and cannot be treated with surgery or radiation meant to cure.

I can provide a recent biopsy of my tumor.

Exclusion Criteria

I don't have any health issues that would make it unsafe for me to take a new drug.

Patient who are receiving any other investigational agents

I have had leptomeningeal disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MGC018 through an intravenous (IV) infusion every 28 days until disease progression or unacceptable toxicity

Approximately 1 year

1 visit every 28 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days after last treatment

Long-term follow-up

Overall survival is assessed from study drug initiation to death

3 years

Treatment Details

Interventions

• MGC018

Trial Overview The study tests if MGC018 can help at least 25% of patients whose ES-SCLC has relapsed or is refractory. It involves regular tumor assessments and blood tests for biomarkers before and during treatment, as well as after disease progression.

Participant Groups

Group I: MCG018 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

MacroGenics

Industry Sponsor

Trials

51

Recruited

5,400+

Findings from Research

The combination of the anti-PD-1 antibody budigalimab and the antibody-drug conjugate Rova-T was found to be tolerated in 31 patients with previously treated small cell lung cancer (SCLC), with common side effects including pleural effusion, fatigue, and cough.

This combination therapy showed an overall response rate of 24.1%, with one complete response and six partial responses, indicating promising efficacy despite the discontinuation of Rova-T's development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Calvo, E., Spira, A., Miguel, M., et al.[2022]

Lorvotuzumab mertansine (LM) effectively targets CD56, which is present in about 74% of small cell lung cancer (SCLC) tumors, demonstrating potent cytotoxicity against these cancer cells in laboratory tests.

In mouse models, LM showed significant anti-tumor activity both as a standalone treatment and in combination with standard chemotherapy, achieving effective results at much lower doses than typically required for monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lorvotuzumab mertansine, a CD56-targeting antibody-drug conjugate with potent antitumor activity against small cell lung cancer in human xenograft models. Whiteman, KR., Johnson, HA., Mayo, MF., et al.[2021]

Four distinct molecular subtypes of small-cell lung cancer (SCLC) were identified, with the SCLC-I subtype showing high levels of immune activation but also associated with platinum resistance, indicating a need for tailored therapies.

BET inhibitors were found to suppress aggressive features in the SCLC-I subtype and may serve as promising candidates to overcome platinum resistance in SCLC treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Subtypes and Tumor Microenvironment Characteristics of Small-Cell Lung Cancer Associated with Platinum-Resistance. Kim, J., Kim, S., Park, SY., et al.[2023]

Small cell lung cancer (SCLC) is a highly aggressive cancer with a very low 5-year survival rate of only 6%, and despite being sensitive to chemotherapy and radiation, treatment options have not significantly improved in nearly 40 years.

Recent advancements in basic and translational research, particularly the development of mouse models, are providing new insights into SCLC metastasis and resistance, highlighting the urgent need for innovative therapeutic strategies and ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Small cell lung cancer: will recent progress lead to improved outcomes? Pietanza, MC., Byers, LA., Minna, JD., et al.[2022]

Small cell lung cancer (SCLC) is a highly aggressive cancer with limited progress in treatment over the past 30 years, primarily relying on platinum-based chemotherapy, which has reached its efficacy limits.

Recent early-phase clinical trials using immune checkpoint inhibitors targeting CTLA-4 and PD-1 have shown promising results, suggesting a potential new direction for treatment in SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint blockade in small cell lung cancer: is there a light at the end of the tunnel? Paglialunga, L., Salih, Z., Ricciuti, B., et al.[2021]

The study identified that overexpression of the cell cycle regulator Wee1 is linked to acquired resistance to the Chk1 inhibitor prexasertib in small cell lung cancer (SCLC), suggesting that targeting Wee1 could enhance treatment efficacy.

Combining Chk1 and Wee1 inhibitors may offer a promising new strategy for overcoming drug resistance in SCLC, as the research demonstrated that manipulating Wee1 levels can reverse resistance to prexasertib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquired small cell lung cancer resistance to Chk1 inhibitors involves Wee1 up-regulation. Zhao, X., Kim, IK., Kallakury, B., et al.[2022]

Oblimersen, an antisense oligonucleotide targeting the bcl-2 oncogene, has been safely combined with chemotherapy, showing potential for improving treatment outcomes in small-cell lung cancer.

While some new agents like bortezomib and anti-angiogenic strategies are under evaluation, only thalidomide has shown a survival benefit when added to chemotherapy, although it comes with significant toxicity concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapies for the treatment of small-cell lung cancer: a time for cautious optimism? Board, RE., Thatcher, N., Lorigan, P.[2018]

In a phase I study involving 33 patients with advanced solid tumors, MG98, an antisense oligonucleotide targeting DNMT1, was found to be well tolerated, with the maximum tolerated dose identified as 200 mg/m²/day and mild side effects like fatigue and myalgia.

Early signs of antitumor activity were observed, with one patient achieving a partial response and another showing prolonged disease stabilization, alongside significant suppression of DNMT1 expression in 26 out of 32 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of MG98, an oligonucleotide antisense inhibitor of human DNA methyltransferase 1, given as a 7-day infusion in patients with advanced solid tumors. Plummer, R., Vidal, L., Griffin, M., et al.[2017]

Whole-exome sequencing of small cell lung cancer (SCLC) samples from 30 patients revealed that relapsed tumors often have specific genetic alterations, including gains in the ABCC1 gene and deletions in MYCL, MSH2, and MSH6, which may contribute to chemoresistance.

The study identified that activation of WNT signaling is a key mechanism driving chemoresistance in relapsed SCLC, as evidenced by increased WNT activity in both relapse samples and in vitro-derived chemoresistant cell lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent WNT pathway alterations are frequent in relapsed small cell lung cancer. Wagner, AH., Devarakonda, S., Skidmore, ZL., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. [2022]

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

Lorvotuzumab mertansine, a CD56-targeting antibody-drug conjugate with potent antitumor activity against small cell lung cancer in human xenograft models. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Molecular Subtypes and Tumor Microenvironment Characteristics of Small-Cell Lung Cancer Associated with Platinum-Resistance. [2023]

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

Small cell lung cancer: will recent progress lead to improved outcomes? [2022]

5. England pubmed.ncbi.nlm.nih.gov

Immune checkpoint blockade in small cell lung cancer: is there a light at the end of the tunnel? [2021]

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

Acquired small cell lung cancer resistance to Chk1 inhibitors involves Wee1 up-regulation. [2022]

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

Novel therapies for the treatment of small-cell lung cancer: a time for cautious optimism? [2018]

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

Phase I study of MG98, an oligonucleotide antisense inhibitor of human DNA methyltransferase 1, given as a 7-day infusion in patients with advanced solid tumors. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Recurrent WNT pathway alterations are frequent in relapsed small cell lung cancer. [2022]