ifinatamab deruxtecan (DS-7300)

P1/2, N=242, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Aug 2029 --> Feb 2030

P1/2, N=232, Active, not recruiting, Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | Recruiting --> Active, not recruiting

P1/2, N=298, Recruiting, Merck Sharp & Dohme LLC | N=228 --> 298

P1/2, N=170, Not yet recruiting, Merck Sharp & Dohme LLC

Novel agents such as tarlatamab (DLL3-targeting) and ifinatamab deruxtecan (B7-H3-targeting) have shown encouraging efficacy in early-phase trials, though predictive markers remain elusive. A multi-dimensional approach combining tissue, blood, and immune profiling is essential to advance precision oncology in SCLC and improve patient selection for emerging therapies.

P2, N=187, Active, not recruiting, Daiichi Sankyo | Trial completion date: Nov 2025 --> Dec 2026

P3, N=540, Active, not recruiting, Daiichi Sankyo | Recruiting --> Active, not recruiting

I-DXd 12 mg/kg Q3W showed promising efficacy in patients with previously treated ES-SCLC. The observed safety profile was consistent with previous reports, with no new safety signals identified.

P1/2, N=250, Recruiting, Daiichi Sankyo | Trial completion date: Mar 2027 --> Oct 2029 | Trial primary completion date: Dec 2025 --> Apr 2027

Patients with small cell lung cancer (SCLC) have poor prognosis and limited treatment options beyond first-line therapy. Secondary endpoints include ORR by investigator; progression-free survival, duration of response, disease control rate, and time to response, all by BICR and investigator; patient-reported outcomes; and safety. IDeate-Lung02 will ascertain whether I-DXd treatment after only one prior line of systemic treatment improves outcomes for patients with relapsed SCLC compared with topotecan, amrubicin, or lurbinectedin.Clinical Trial Registration: NCT06203210.

For decades, outcomes stagnated: most patients present with extensive-stage disease, screening rarely detects early tumors, surgery is seldom feasible, and platinum-etoposide remained the first-line standard with median overall survival (OS) 80% of SCLC, enables T-cell-redirecting therapy: the bispecific T-cell engager tarlatamab improved OS to 13.6 vs 8.3 months over standard second-line chemotherapy, with manageable cytokine release syndrome and occasional ICANS. B7 homolog 3 (B7-H3, CD276), uniformly expressed across SCLC subtypes and linked to poor prognosis, is another compelling target: the antibody-drug conjugate ifinatamab deruxtecan achieved a 54.8% response rate and meaningful survival in heavily pretreated patients, earning FDA Breakthrough designation. Together, DLL3- and B7-H3-directed therapies (with additional ADCs against Trop-2 and SEZ6 in development) are redefining second-line and later care. Key next steps include optimizing sequencing/combination strategies, managing BiTE-specific toxicities, and developing predictive biomarkers. After decades of futility, SCLC is transitioning from uniform chemotherapy to a precision-medicine paradigm with cautious optimism.

P2, N=96, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Sep 2030 --> Mar 2032