Immunotherapies for Lung Cancer: Recent Approvals

The number of immuno-oncology treatments has dramatically increased during the last 9 years. The majority of these agents are immune checkpoint inhibitors, which allow T-cell activation for the recognition and killing of tumor cells. Many tumors are able to evade recognition by the immune system, and specifically T cells, by activating “checkpoints” that cause T cells to ignore the tumor cells.

Currently, there are 6 different immune checkpoint inhibitors approved by the US Food and Drug Administration (FDA) for the treatment of different cancers: atezolizumab, avelumab, durvalumab, ipilimumab, nivolumab, and pembrolizumab. All of these agents, except avelumab, are approved for the treatment of advanced lung cancers without genetic aberrations (such as in the EGFR or ALK genes). Most recently in 2020, the FDA approved additional immune checkpoint inhibitor combinations for the treatment of advanced lung cancer:¹

• Nivolumab plus ipilimumab for the first-line treatment of non-small cell lung cancer (NSCLC) with 1% or higher PD-L1 expression
• Nivolumab plus ipilimumab and 2 cycles of platinum-doublet chemotherapy for first-line treatment of NSCLC
• Atezolizumab monotherapy for the first-line treatment of NSCLC with 50% or higher PD-L1 expression
• Durvalumab plus etoposide and carboplatin or cisplatin for the treatment of extensive-stage small-cell lung cancer (SCLC).

These are in addition to FDA approvals of targeted therapy, which are used to treat lung cancers with genetic aberrations. Overall, as of July 2020, the FDA has approved 10 different regimens for the treatment of advanced NSCLC or SCLC (Table).¹

Table. FDA Approvals for Lung Cancer in 2020¹

Tumor Type	Drug Class	Agent	Comments
NSCLC	Targeted therapy	Capmatinib	MET exon 14 skipping mutation
Selpercatinib	RET fusion–positive
Ramucirumab + erlotinib	EGFR exon 19 deletion or exon 21 (L858R) mutations
Brigatinib	ALK-positive
Immunotherapy	Nivolumab + ipilimumab	≥1% PD-L1 expression
Nivolumab + ipilimumab + 2 cycles platinum-doublet chemotherapy	First-line
Atezolizumab	≥50% PD-L1 expression
SCLC	Targeted therapy	Lurbinectedin	After progression on/after platinum-based chemotherapy
Immunotherapy	Durvalumab + etoposide + carboplatin or cisplatin	Extensive-stage SCLC

However, the field is also evaluating other types of immuno-oncology agents.

Beyond Immune Checkpoint Inhibitors

Many of the immuno-oncology agents in development use either adoptive cell therapy or personalized cancer vaccines.²  Some examples of ongoing clinical trials evaluating these types of immuno-oncology agents include:

• Phase 1 trial of tumor-infiltrating lymphocytes (TIL) in combination with nivolumab (ClinicalTrials.gov Identifier: NCT03215810)³
• Phase 2 trial of chimeric antigen receptor (CAR) T- cell (CAR-T) therapies for the treatment of mesothelioma (ClinicalTrials.gov Identifier: NCT02414269)⁴
• Phase 1 trial of T cell receptor (TCR) immunotherapy for NSCLC (ClinicalTrials.gov Identifier: NCT03247309)⁵
• Phase 1/2 trial of a peptide vaccine for NSCLC (ClinicalTrials.gov Identifier: NCT01720836)⁶