M7824 in Combination With Chemotherapy in Stage IV Non-small Cell Lung Cancer (NSCLC)

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Carboplatin; Drug: Nab-paclitaxel; Drug: Gemcitabine; Drug: Bintrafusp alfa; Drug: Cisplatin; Drug: Docetaxel; Drug: Paclitaxel; Drug: M7824; Drug: Pemetrexed

Study type: Interventional

Funder types: Industry

Identifiers

NCT03840915

MS200647_0024

2018-004040-28 (EudraCT Number)

Details and patient eligibility

About

The main purpose of the study was to evaluate the safety and tolerability of M7824 in combination with chemotherapy.

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants greater than or equals to (>=) 18 years of age inclusive at the time of signing the informed consent

• Participants who have histologically confirmed diagnosis of Stage IV NSCLC:

  1. Participants in Cohort A, B, and C must not have received prior systemic therapy treatment for their Stage IV NSCLC
  2. Participants who had disease progression on previous treatment with Programmed death-ligand 1 (PD- L1) inhibitors in combination with platinum-based chemotherapy are enrolled in Cohort D, as long as therapy was completed at least 28 days of the first study intervention.

• Have measurable disease based on Response evaluation criteria in solid tumors (RECIST) 1.1

• Have a life expectancy of at least 3 months

• Availability of archived tumor material (less than [<] 6 months old) adequate for biomarker analysis is mandatory at Screening, central laboratory confirmation is required. Fresh biopsies should be collected if archived tumor material is not available

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at study entry and date of first dose

Exclusion criteria

• The participant's tumor harbors an epidermal growth factor receptor (EGFR) sensitizing (activating) mutation,ROS1 rearrangement, or BRAF V600E mutation or anaplastic lymphoma kinase (ALK) positive, if targeted therapy is locally approved
• Mixed small cell with NSCLC cancer histology
• Has received major surgery within 4 weeks prior to the first dose of study intervention; received thoracic radiation therapy (RT) of > 30 gray (Gy) within 6 months prior to the first dose of study intervention
• Previous malignant disease (other than the target malignancy to be investigated in this study) within the last 3 years
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks after the end of the RT and, have no evidence of new or enlarging brain metastases evaluated by imaging, preferably brain magnetic resonance imaging (MRI)
• Known severe hypersensitivity to study intervention or any components in their formulations
• For participants in Cohort A, B and C: Has received prior systemic therapy for Stage IV NSCLC, including anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Unable to tolerate computed tomography (CT) or MRI in the opinion of the Investigator and/or allergy to contrast material.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 4 patient groups

Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa

Experimental group

Description:

Participants received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin or Carboplatin, and Pemetrexed every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

Treatment:

Drug: Carboplatin

Drug: Cisplatin

Drug: M7824

Drug: Pemetrexed

Drug: Carboplatin

Drug: Carboplatin

Cohort B: Carboplatin + Paclitaxel or Nab-paclitaxel + Bintrafusp alfa

Experimental group

Description:

Participants received 2400 mg Bintrafusp alfa along with Carboplatin, and Paclitaxel or Nab-paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

Treatment:

Drug: Carboplatin

Drug: Paclitaxel

Drug: Bintrafusp alfa

Drug: Carboplatin

Drug: Nab-paclitaxel

Drug: Carboplatin

Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa

Experimental group

Description:

Participants received 2400 mg Bintrafusp alfa along with Cisplatin or Carboplatin, and Gemcitabine every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

Treatment:

Drug: Carboplatin

Drug: Cisplatin

Drug: Gemcitabine

Drug: Bintrafusp alfa

Drug: Carboplatin

Drug: Carboplatin

Cohort D: Docetaxel + Bintrafusp alfa

Experimental group

Description:

Participants received 2400 mg Bintrafusp alfa along with Docetaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

Treatment:

Drug: Docetaxel

Drug: Bintrafusp alfa