The European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted positive opinions for two drugs for the treatment of adults with small cell lung cancer (SCLC).

The first, Imdylltra (tarlatamab, Amgen), is a new treatment for relapsed extensive-stage SCLC, which the CHMP said addresses an unmet medical need in adults with poor prognosis and limited treatment options. 

The second is Zepzelca (lurbinectedin, PharmaMar). It is indicated for maintenance treatment in patients with extensive-stage SCLC whose disease has not progressed after first-line induction therapy.

SCLC is a rare, rapidly growing cancer associated with a poor prognosis. Whilst many patients initially benefit from treatment with platinum-based chemotherapy, relapse is common. Treatment options following relapse are limited and outcomes remain poor, the CHMP emphasized, which highlighted the need for new treatment options. 

Risk for Death Reduced by 40% 

Imdylltra is used as monotherapy to treat adults with extensive-stage SCLC whose disease relapsed during or after an initial treatment with platinum-based chemotherapy. The CHMP said the treatment provides a new targeted immunotherapy approach for these patients.

The active substance of Imdylltra is tarlatamab, an antineoplastic agent. Tarlatamab is a bispecific T-cell engager targeting DLL3, an oncogenic protein aberrantly expressed by SCLC tumor cells, and CD3 expressed by T cells. It binds to DLL3 on tumor cells and CD3 on T cells, bringing them into close proximity. This activates T cells and leads to the production of inflammatory cytokines and the release of cytotoxic proteins, resulting in tumor cell death.

Imdylltra will be available as a 1-mg and 10-mg powder for concentrate and solution for infusion.

The EMA based its recommendation on a randomized, open-label, phase 3 study in adults with extensive-stage SCLC whose cancer had relapsed after an initial treatment with platinum-based chemotherapy. Participants received either tarlatamab or standard-of-care chemotherapy (topotecan, lurbinectedin, or amrubicin).

Those treated with tarlatamab had a median overall survival of 13.6 months, compared with 8.3 months for those given standard of care. This corresponded with a 40% reduction in the risk for death for those treated with tarlatamab. The median progression-free survival was 4.2 months in people treated with tarlatamab compared with 3.2 months in those given standard-of-care treatment.

The most common and serious side effects with tarlatamab are cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Other common side effects include decreased appetite and pyrexia.

Longer Survival 

Zepzelca, in combination with atezolizumab, is indicated for maintenance treatment in adults with extensive-stage SCLC whose disease has not progressed after first-line induction therapy with atezolizumab, carboplatin, and etoposide.

Its active substance is the antineoplastic agent lurbinectedin. It inhibits the oncogenic transcription process by binding to CG-rich DNA sequences, evicting transcription factors from their binding sites and stalling elongating RNA polymerase II and its degradation by the ubiquitin/proteasome machinery. This leads to cell cycle arrest and tumor cell apoptosis.

In the IMforte study, progression-free survival and overall survival were longer for patients with extensive-stage SCLC treated with lurbinectedin in combination with atezolizumab than those treated with atezolizumab alone.

Zepzelca will be available as a 2-mg and 4-mg powder for concentrate for solution for infusion. Its most common side effects are nausea, fatigue, anemia, thrombocytopenia, and neutropenia.

Rob Hicks is a retired National Health Service doctor. A well-known TV and radio broadcaster, he has written several books and has regularly contributed to national newspapers, magazines, and online publications. He is based in the United Kingdom.