Table 1.

Optimization of neoadjuvant immunotherapy in early phase trials

	Melanoma	Gastrointestinal malignancies*	Gynecologic malignancies	Non-small cell lung cancer	Head and neck malignancies
Outcome measures	pCR (preferred)† EFS ORR RFS OS	pCR DFS EFS	pCR (not well defined) ORR EFS	pCR (preferred) MPR EFS OS	pCR/MPR/LPR ORR RFS EFS
Duration of neoadjuvant phase	6–12 weeks‡	6–17 weeks	9–12 weeks	4–12 weeks	3–6 weeks
Comparators in randomized trials	Anti-PD-1§ Ipi1–Nivo3 Rela–Nivo	Chemotherapy Chemoradiation Anti-PD-L1 Observation	Chemotherapy (EOC, EC, Cx) Chemoradiation (Cx)	Platinum doublet chemotherapy	Anti-PD-1 Anti-PD-1/CTLA-4
Adjuvant therapy	Preferred¶	Preferred	Preferred	Adjuvant therapy given in all but one (CheckMate 816) of the phase 3 trials	Pathologic risk-adapted adjuvant therapy
Biospecimens for biomarker studies	Baseline At surgery Follow-up	Baseline At surgery Follow-up	Baseline At surgery Follow-up	Serial circulating tumor DNA Baseline At surgery Follow-up	Baseline At surgery Follow-up

*Dependent on primary tumor type.

†pCR is the preferred endpoint in early phase trials in melanoma. EFS, RFS and OS become more important for large, randomized trials.

‡Duration may be tailored based on the expected clinical activity of the agent(s) being tested. An interim clinical assessment may be planned if there are concerns about disease progression.

§Anti-PD-1 monotherapy, ipilimumab 1 mg/kg+nivolumab 3 mg/kg, relatlimab–nivolumab.

¶Studies may consider randomizing patients who achieve a pCR to observation versus continued systemic adjuvant therapy.

CTLA-4, cytotoxic T-lymphocytes-associated protein 4; Cx, cervix; DFS, disease-free survival; EC, endometrial cancer; EFS, event-free survival; EOC, epithelial ovarian cancer; LPR, laryngopharyngeal reflux; MPR, major pathologic response; ORR, overall response rate; OS, overall survival; pCR, pathologic complete response; PD-1, programmed cell death protein-1; PD-L1, programmed death-ligand 1; RFS, recurrence-free survival.