M7824 + Chemotherapy for Small Cell Lung Cancer
Trial Summary
Do I have to stop taking my current medications to join the trial?
The trial protocol does not specify if you must stop taking your current medications. However, you must not have received chemotherapy or undergone major surgery within 2 weeks, and radiotherapy within 24 hours prior to enrollment. You also cannot be on any other investigational agents. It's best to discuss your current medications with the trial team to ensure eligibility.
What data supports the idea that M7824 + Chemotherapy for Small Cell Lung Cancer is an effective treatment?
The available research does not provide specific data on the effectiveness of M7824 combined with chemotherapy for small cell lung cancer. Instead, it discusses other treatments like temozolomide with olaparib and topotecan with ifosfamide or etoposide. These studies suggest that while there are some promising combinations for treating small cell lung cancer, there is no direct evidence from the provided information about the effectiveness of M7824 with chemotherapy for this condition.12345
What safety data exists for M7824 + chemotherapy in small cell lung cancer?
The safety data for temozolomide, a component of the treatment, indicates it has a good safety profile with nonoverlapping toxicities and is generally well-tolerated. Common side effects include fatigue, nausea, vomiting, thrombocytopenia, and neutropenia, while severe myelosuppression is uncommon. Rare cases of severe hematological effects like aplastic anemia have been reported. The combination of temozolomide with other agents like carmustine and irinotecan has shown additive or synergistic effects with manageable toxicity levels. However, specific safety data for M7824 (Bintrafusp alfa) combined with chemotherapy in small cell lung cancer is not detailed in the provided research.678910
Is the drug M7824, Temozolomide, Topotecan a promising treatment for small cell lung cancer?
Yes, the drug combination of M7824, Temozolomide, and Topotecan shows promise for treating small cell lung cancer. Research indicates that these drugs can be effective, especially in patients who have relapsed or have not responded to other treatments. Temozolomide, in particular, has shown potential when combined with other drugs, and Topotecan has been active in treating this type of cancer. These findings suggest that this drug combination could be a valuable option for patients.14111213
What is the purpose of this trial?
BACKGROUND:* Small cell lung cancer (SCLC) is an aggressive cancer with a poor prognosis. Although highly responsive to chemotherapy initially, SCLC relapses quickly and becomes refractory to treatment within a few months.* The inability to destroy residual SCLC cells despite initial chemosensitivity suggests the existence of a highly effective deoxyribonucleic acid (DNA) damage response network. SCLC is also characterized by high DNA replication stress (retinoblastoma (RB1) inactivation, MYC and CCNE1 activation).* There is only one Food and Drug Administration (FDA) approved treatment for patients with relapsed SCLC after first-line chemotherapy: topotecan, which inhibits religation of topoisomerase I-mediated single-strand DNA breaks leading to lethal double-strand DNA breaks. Temozolomide, an oral alkylating agent, which causes DNA damage by alkylating guanine at position O6 also has activity in relapsed SCLC, particularly for brain metastases.* Preliminary evidence indicates that disruption of the immune checkpoint programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway can yield responses in a subset of SCLC patients, but response rates (approximately equal to 10%) are lower than non-small cell lung cancer (NSCLC) and other tumors with comparable tumor mutational burden indicating additional immunosuppressive mechanisms at play in the SCLC tumor microenvironment.* M7824 (MSB0011359C) is a bifunctional fusion protein consisting of an anti-programmed death ligand 1 (PDL1) antibody and the extracellular domain of transforming growth factor beta (TGF-beta) receptor type 2, a TGF-beta trap.* Safety data from the dose-escalation study in solid tumors as well as preliminary data from expansion cohorts show that M7824 has a safety profile similar to other checkpoint inhibiting compounds.* Combining immunotherapy, and chemotherapy could synergistically improve the anticancer activity of immunotherapy. Combination of chemotherapy with immunotherapy have improved outcomes in NSCLC and melanoma leading to Food and Drug Administration (FDA) approvals of such combinations.* We hypothesize that increased DNA damage induced by topotecan and temozolomide will complement the anti-tumor activity of M7824, in recurrent SCLC.OBJECTIVE:- The primary objective of the trial is to determine the efficacy (using objective response rate) of M7824 plus topotecan or temozolomide in relapsed SCLC.ELIGIBILITY:* Subjects with histological or cytological confirmation of SCLC.* Subjects must be greater than or equal to 18 years of age and have a performance status (Eastern Cooperative Oncology Group (ECOG) less than or equal to 2.* Subjects must not have received chemotherapy or undergone major surgery within 2 weeks and radiotherapy within 24 hours prior to enrollment.* Subjects must have adequate organ function and measurable disease.DESIGN:* Arm A (M7824 monotherapy): Up to 10 patients may be treated with M7824 monotherapy to obtain safety and pharmacokinetic (PK) data, and a preliminary estimate of clinical responses to M7824 in SCLC. Patients with progressive disease on Arm A may then receive M7824 plus temozolomide as per description of treatment for Arm C.* Arm B (M7824 plus topotecan) and Arm C (M7824 plus temozolomide) will be administered in 3 and 4-week cycles respectively; these arms will have a safety run-in followed by efficacy analysis. Up to 10 patients with extrapulmonary small cell cancer will be enrolled in arm C to receive the combination of M7824 and temozolomide.* Optional tumor biopsies will be obtained at pre-treatment on cycle 1 day 1 (C1D1) and C1D15 for Arm C; pre-treatment on C1D1 and cycle 2 day 1 (C2D1) for arms A and B.* Every subject of each arm of the safety run-in will be observed for at least 7 days after first dose of M7824 before the subsequent subject can be treated. Subjects who are not evaluable for dose-limiting toxicity (DLT) will be replaced and not included into evaluation.ARMS:* Arm A (3-week cycles): M7824 monotherapy 2400 mg every 3 weeks until disease progression or a criterion in Protocol is met. Patients with progressive disease on Arm A may then receive 1200 mg M7824 every 2 weeks plus temozolomide 200 mg/m\^2/day on days 1-5 every 4 weeks.* Arm B (3-week cycles): M7824 2400 mg plus topotecan 1 mg/m(2) on days 1-5 every 3 weeks until disease progression or a criterion in Protocol is met.* Arm C (4-week cycles): M7824 1200 mg every 2 weeks plus temozolomide 200 mg/m(2)/day on days 1-5 every 4 weeks until disease progression or a criterion in Protocol is met.
Research Team
Anish Thomas, M.D.
Principal Investigator
National Cancer Institute (NCI)
Eligibility Criteria
This trial is for adults over 18 with relapsed Small Cell Lung Cancer (SCLC) who've had at least one chemotherapy treatment and whose cancer has progressed after immunotherapy. They should not have had chemo, major surgery within the last 2 weeks, or radiotherapy in the past 24 hours. Participants need to be physically capable of undergoing treatment (ECOG ≤2), have measurable disease, and proper organ function.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Safety Run-In
Initial safety assessment of M7824 monotherapy and combination therapies with topotecan or temozolomide
Treatment
Participants receive M7824 monotherapy or combination therapy with topotecan or temozolomide in 3 or 4-week cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- M7824
- Temozolomide
- Topotecan
M7824 is already approved in United States, European Union for the following indications:
- Biliary tract cancer
- No approved indications listed; under investigation for various cancers
Find a Clinic Near You
Who Is Running the Clinical Trial?
National Cancer Institute (NCI)
Lead Sponsor