EVIDENCE CARD · NCT06976190 · NPC landscape

MRG003 + Pucotenlimab vs Chemotherapy in Recurrent/Metastatic Nasopharyngeal Carcinoma

A multicenter randomized Phase 3 trial (Lepu Biopharma) testing becotatug vedotin (EGFR-directed ADC) plus pucotenlimab (anti-PD-1) vs investigator's-choice chemotherapy in patients with R/M NPC.

Evidence: Moderate–High

Phase 3, N = 446, randomized 1:1, recruiting since May 2025. Combo regimen is supported by N = 31 Phase 1/2 cohort (ORR 71%, mPFS 12 mo, JCO 2026), and the MRG003 backbone has N = 173 randomized Level II data vs chemotherapy (ORR 30.2% vs 11.5%, mPFS 5.82 vs 2.83 mo, HR 0.63; Ann Oncol 2026). MRG003 monotherapy was approved in China (Oct 2025) for R/M NPC after ≥2 lines chemo + PD-1/PD-L1. Primary completion expected May 2029.

Phase

Enrollment

446 (target)

Design

Randomized 1:1, open-label

Status

Recruiting

First posted

2025-05-16

Primary completion

May 2029

Primary endpoints

PFS (BIRC), OS

Sponsor

Lepu Biopharma

Evidence supporting this trial

Combo regimen (MRG003 + pucotenlimab)

Pivotal Ph1/2 Same combo Becotatug Vedotin + Pucotenlimab in Platinum- and IO-Resistant R/M NPC

Ruan DY et al. J Clin Oncol 2026 Aug · Magic-C001 (NCT05688605) Phase 1/2 dose-expansion NPC cohort · PMID 42641116

Patients (RP2D, NPC)
31

Confirmed ORR
71.0% (52.0–85.8)

Disease control rate
93.5% (78.6–99.2)

Median DoR
14.0 mo

Median PFS
12.0 mo (6.8–15.4)

Median OS
Not mature

Grade ≥3 TRAE
40.6%

Treatment-related deaths
0

Backbone (MRG003 monotherapy) — how the ADC alone performs vs chemotherapy

Level II randomized MRG003 vs chemotherapy in ≥2L R/M NPC (Magic-M001 randomized cohort)

Han F et al. Ann Oncol 2026 Jun · Multicenter, open-label, 1:1 randomized · PMID 42309209

Randomized
173 (86 MRG003 / 87 chemo)

ORR
30.2% vs 11.5% (p=0.003)

Median PFS
5.82 vs 2.83 mo (HR 0.63)

Median OS (interim)
17.08 vs 11.99 mo (HR 0.73, p=0.15)

Follow-up
13.5 mo

Safety
Comparable to chemo
Superseded MRG003 monotherapy Phase IIa single-arm in R/M NPC

Han F et al. Med 2026 Apr · NCT05126719 · PMID 41720100 · Note: this dataset was later expanded into the randomized readout above; the Level II Ann Oncol 2026 readout supersedes this single-arm reading.

Patients
61

IRC-assessed ORR
42% (30–56)

Median DoR
8.0 mo

Median PFS
5.8 mo

Median OS (all)
15.8 mo (11.0–NE)

Median OS (2.3 mg/kg)
25.2 mo (11.0–NE)

Grade ≥3 TRAE
39%
First-in-human MRG003 Phase 1a/1b in advanced solid tumors (NPC subset)

Qiu MZ et al. JAMA Oncol 2022 Jul · NCT04868344 · PMID 35511148

Patients (all)
61 (Ph1a 22 + Ph1b 39)

NPC ORR (Ph1b)
44%

NPC DCR (Ph1b)
89%

Grade ≥3 TRAE
31%

Recommended dose
2.5 mg/kg Q3W

Regulatory

Approved · China MRG003 (Meiyouheng) — first approval, October 2025

Blair HA. Drugs 2026 Apr · First-approval review · PMID 41787195

Approved in China for adult patients with R/M NPC who have failed at least two lines of systemic chemotherapy AND PD-1/PD-L1 inhibitor therapy. (This is a monotherapy label — the Phase 3 studied here would move MRG003 into a combo, further-line-agnostic setting.)

Timeline

2018 Apr

Phase 1a first-in-human enrollment (MRG003-001)

2022 Jul

Phase 1a/1b readout — MRG003 in solid tumors, NPC ORR 44% (JAMA Oncol, PMID 35511148)

2025 Oct

China approval — MRG003 for R/M NPC after ≥2L chemo + PD-1/PD-L1 (Meiyouheng)

2025 May

NCT06976190 registered — Phase 3 MRG003+Pucotenlimab vs chemo, N=446

2026 Apr

Phase IIa monotherapy single-arm readout — N=61, ORR 42% (Med, PMID 41720100) · superseded by the randomized readout below

2026 Jun

Randomized backbone readout — Magic-M001, N=173, ORR 30.2% vs 11.5%, mPFS HR 0.63 (Ann Oncol, PMID 42309209)

2026 Aug

Combo readout — MRG003+Pucotenlimab NPC cohort, N=31, ORR 71% (JCO, PMID 42641116) — the direct rationale for NCT06976190

2029 May

Expected primary completion (PFS, OS)

How this strength score was computed

Dimension	Score	Basis
Study design	Moderate–High	Backbone: Level II (randomized, open-label). Combo: single-arm Ph1/2 dose-expansion cohort (Level III). Overall: mixed but with randomized anchor.
Sample size	Moderate	Backbone N = 173 randomized; combo N = 31 subset at RP2D. Adequate for signal, small for confirmatory.
Follow-up maturity	Moderate	Backbone: 13.5 mo median follow-up, interim OS not statistically significant yet. Combo: DoR mature (14 mo) but OS not mature.
Source quality	High	J Clin Oncol, Ann Oncol (both top-tier peer-reviewed) + Drugs first-approval review + JAMA Oncol first-in-human. Regulatory approval in one geography.
Endpoint quality	High	BIRC-adjudicated ORR + PFS on backbone; ORR + DoR + PFS on combo. OS not yet mature.
Consistency	Moderate	ORR range 30% (2L+, backbone) → 42% (Ph2a single-arm) → 44% (Ph1b) → 71% (combo, IO-resistant). PFS gain consistent across regimens.

Limitations of this evidence base:

Direct evidence for the combo regimen (MRG003 + pucotenlimab) is a single Phase 1/2 cohort of N = 31. The randomized Phase 3 exists precisely because that N is small.
Backbone monotherapy data is Level II randomized, but the interim OS gain did NOT reach statistical significance (HR 0.73, p = 0.15) at the reported cut-off.
All published evidence is from Chinese centers (predominantly Sun Yat-sen and Hunan Cancer Hospital). Generalizability to non-endemic (Type I / Western) NPC populations is untested.
Regulatory approval covers MRG003 monotherapy, ≥2L, after chemo + PD-1/PD-L1 failure. The Phase 3 studied here is a different regimen and possibly a different line.
ORR reads across regimens/lines are difficult to compare (30% in ≥2L monotherapy vs 71% in the same-line combo after PD-1/PD-L1 failure — different populations).

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Evidence current through September 2026. This card is compiled from ClinicalTrials.gov v2 + PubMed abstracts; hand-check against the linked primary sources for clinical decision-making. Not medical advice.

Sources on this card: PMID 42641116 · 42309209 · 41720100 · 35511148 · 41787195 · CT.gov NCT06976190

Related recruiting MRG003 trials in the ClinTrialFinder corpus: NCT05688605 (Phase 1/2 combo) · NCT05751512 (Phase 3, HNSCC) · NCT06530914 (Phase 2 neoadj)