ASCO 2025 Top 10 Clinical Breakthrough Products

Product: ZG005

Drug Target + Type: PD-1/TIGIT bispecific antibody

Company: Zelgen Biopharmaceuticals Co., Ltd.

This announcement includes results from a Phase I/II study divided into two parts: Part 1 is a dose escalation study, and Part 2 evaluates the efficacy and safety of ZG005 (10 mg/kg or 20 mg/kg) combined with chemotherapy ± bevacizumab.

As of December 19, 2024, Part 1 and Part 2 enrolled 12 and 29 patients with advanced cervical cancer, respectively, with 53.7% of patients receiving bevacizumab during the study. Among 28 evaluable patients, the unconfirmed objective response rate (ORR) was 69.2% (9/13) for the 10 mg/kg group and 80.0% (12/15) for the 20 mg/kg group.

No dose-limiting toxicity (DLT) was observed in Part 1. Safety assessment in 41 patients showed treatment-related adverse events (TRAE) occurred in 75.6% (31/41), mostly grade 1-2 TRAE; grade 3 or higher TRAE incidence was 29.3% (12/41). No patients discontinued treatment or died due to TRAE. One serious adverse event (SAE) of bilateral pneumonia was reported in the 10 mg/kg group; no SAE occurred in the 20 mg/kg group.

Product: Aidotinib (TY-9591)

Drug Target + Type: EGFR T790M inhibitor

Company: TYK Medicines, Inc

The Phase II study enrolled 29 patients with non-small cell lung cancer (NSCLC) brain metastases, including 27 EGFR-sensitive mutation (19 Del and L858R) patients who were EGFR-TKI treatment-na?ve and 2 EGFR-resistant mutation (EGFR T790M) patients. Median follow-up was 16.4 months as of March 21, 2024.

Investigator-assessed intracranial objective response rate (iORR) was 93.1%, with 92.6% in EGFR-sensitive patients. EGFR-resistant patients achieved intracranial partial response (iPR). Median intracranial duration of response (iDOR) and intracranial progression-free survival (iPFS) were not reached; 82.8% had iDOR ≥ 12 months and 96.6% had iPFS ≥ 12 months. Overall median PFS was 13.5 months; EGFR-sensitive subgroup median PFS was 15.1 months.

Safety: TRAE incidence was 93.1% (27/29); grade ≥3 TRAE incidence was 27.6% (8/29). No grade 4-5 adverse events occurred. SAE incidence was 17.2% (5/29). No cases of interstitial pneumonia, cardiomyopathy, or keratitis were reported.

Product: TQB2102

Drug Target + Type: HER2 bispecific antibody-drug conjugate (ADC)

Company: CTTQ

At ASCO, three studies of TQB2102 were selected, two with data disclosed.

Solid tumor Phase I study: As of October 1, 2024, 181 solid tumor patients (80 metastatic breast cancer, 37 colorectal cancer, 23 gastric cancer, 41 others) were treated. 41 patients participated in dose escalation (1.5-9 mg/kg), 140 in dose expansion (6 or 7.5 mg/kg). Median follow-up was 8.15 months. No DLT or maximum tolerated dose (MTD) reached. Among 165 evaluable patients, ORR was 41.2% (all partial responses, PR). Among 7 HER2-positive breast cancer patients with brain metastases, PR was achieved; 1 patient achieved complete remission (CR) after 4 cycles.

HER2 low-expression breast cancer Phase Ib study: 73 chemotherapy-treated patients received TQB2102 monotherapy (37 at 6 mg/kg, 36 at 7.5 mg/kg). Median follow-up 7.16 months. Overall ORR was 53.4% (39/73); 48.7% at 6 mg/kg, 58.3% at 7.5 mg/kg; disease control rate (DCR) 86.3% (63/73). Hormone receptor (HR)-positive and HR-negative subgroups had ORRs of 54.0% and 52.2%, respectively. In the 7.5 mg/kg group, HR-positive and HR-negative ORRs were 66.7% and 46.7%. Among patients previously treated with ADCs, ORR was 44.4%. Safety: TRAE rate 97.3% (71/73); grade ≥3 TRAE 41.1% (30/73); SAE rate 17.8% (13/73). No interstitial pneumonia reported.

Product: TQB2868

Drug Target + Type: PD-1/TGF-β bispecific antibody

Company: CTTQ

The Phase II study evaluated TQB2868 combined with anlotinib, albumin-bound paclitaxel, and gemcitabine as first-line therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC). 40 patients enrolled; 36 were evaluable for efficacy.

Median follow-up was 5.9 months; median PFS and OS were not reached. Six-month PFS and OS rates were 86% and 95%, respectively. ORR was 63.9% (23/36 all PR); DCR was 100%. Exploratory analysis showed >90% inhibition of TGF-β1 post-treatment with minimal rebound.

Product: HLX43

Drug Target + Type: PD-L1 antibody-drug conjugate (ADC)

Company: Henlius Biotech

The Phase I study was divided into two parts.

Part 1 enrolled 18 patients with advanced/metastatic solid tumors refractory or unsuitable for standard therapy, including 12 NSCLC, and others with various squamous cell carcinomas and sarcomas. Investigator-assessed ORR was 31.3%.

Part 2 enrolled 21 advanced/metastatic NSCLC patients refractory to standard therapy (15 squamous, 6 non-squamous). ORR and DCR were 38.1% and 81.0%, respectively; 8 patients (6 squamous, 2 non-squamous) achieved PR.

Results indicate HLX43 is well tolerated at different doses and shows preliminary efficacy in heavily pretreated advanced solid tumors including NSCLC.

Product: Satri-cel/CT041

Drug Target + Type: CLDN 18.2 CAR-T therapy

Company: CARsgen Therapeutics

This is a China-based open-label, multicenter, randomized controlled trial comparing Satri-cel/CT041 (n=104) with standard of care (SOC, n=52) in CLDN 18.2-positive advanced gastric/gastroesophageal junction cancer (G/GEJC) patients who failed at least second-line treatment.

20 SOC patients subsequently received CT041. Data cutoff: October 18, 2024.

In the intention-to-treat (ITT) population, CT041 significantly prolonged progression-free survival (PFS) versus SOC (3.25 vs 1.77 months; HR=0.366; p<0.0001), reducing risk of progression/death by 63%. Overall survival (OS) showed benefit trend (7.92 vs 5.49 months; HR=0.693; one-sided p=0.0416), despite 15.4% of CT041 patients not receiving infusion and nearly 40% of SOC patients receiving CT041 later. In the modified ITT (mITT), median PFS was 4.37 vs 1.84 months (HR=0.304), and median OS was 8.61 vs 5.49 months (HR=0.601), with risk reductions of 70% and 40%, respectively.

Safety was manageable with 4 cases of grade 3 cytokine release syndrome (CRS), no grade 4-5 CRS, and no immune effector cell-associated neurotoxicity syndrome (ICANS). This is the first global confirmatory randomized trial of CAR-T in solid tumors.

Product: LBL-024

Drug Target + Type: PDL1/4-1BB bispecific antibody

Company: Leads Biolabs

The presented results are from an Ib/II study. The Ib dose escalation enrolled previously untreated advanced extrapulmonary neuroendocrine carcinoma (EP-NEC) and small cell lung cancer (SCLC) patients; the II dose optimization/expansion enrolled previously untreated advanced EP-NEC patients.

As of December 26, 2024, 53 patients (Ib 13, II 40) were treated. Among 49 evaluable patients, ORR was 77.6% and DCR 93.9%. In 21 EP-NEC patients, ORR was 81.0% and DCR 95.2%. Two SCLC patients both achieved ORR. Safety and efficacy suggest LBL-024 combined with chemotherapy is well tolerated and shows superior efficacy in EP-NEC compared to historical rates (~30%-55%).

Product: Lucitanib Satozumab

Drug Target + Type: TROP2 ADC

Company: Kelun-Biotech

Four clinical studies of Lucitanib Satozumab were presented at ASCO, with two highlighted here.

Phase III OptiTROP-Lung03 study: Enrolled 137 advanced EGFR-mutated NSCLC patients progressed after EGFR-TKI and platinum chemotherapy. Median follow-up 12.2 months showed BIRC-assessed confirmed ORR (cORR) of 45.1% vs 15.6% (docetaxel; p=0.0004), median PFS 6.9 vs 2.8 months (HR=0.30; p<0.0001). Investigator-assessed median PFS was 7.9 vs 2.8 months (HR=0.23). OS was not reached in either arm, with HR=0.49 (p=0.007). Adjusted OS analysis estimated 9.3 months in docetaxel arm vs not reached in Lucitanib Satozumab arm (HR=0.36).

Phase II OptiTROP-Breast05 study: Included 41 untreated unresectable locally advanced or metastatic triple-negative breast cancer (a/m TNBC) patients (43.9% ECOG PS=1; 78% PD-L1 CPS<10). Median follow-up 18.6 months: ORR 70.7%, DCR 92.7%, duration of response 12.2 months, median PFS 13.4 months. In PD-L1 CPS<10 subgroup (n=32), ORR 71.9%, DCR 93.8%, median PFS 13.1 months.

Product: ZG006

Drug Target + Type: CD3/DLL3 trispecific antibody

Company: Zelgen Biopharmaceuticals Co., Ltd.

A Phase I trial enrolled 16 SCLC patients progressing after platinum-based chemotherapy. As of November 28, 2024, median follow-up was 2.2 months.

Confirmed ORR was 50.0%, with 1 complete remission (CR) and 7 partial responses (PR). Disease control rate (DCR) was 87.5%, median duration of response (DoR) was 3.7 months, and median progression-free survival (PFS) was 3.4 months.

All patients experienced TRAE, with grade 3 TRAE in 31.3%, no grade 4 or 5 TRAE. CRS occurred in 87.5% (1 grade 4). No neurotoxicity was observed.

Product: Camrelizumab (HS-10296) + Lenvatinib

Drug Target + Type: PD-1 inhibitor + VEGFR inhibitor

Company: Hengrui Pharmaceuticals

A randomized Phase III trial enrolled 336 first-line advanced or metastatic hepatocellular carcinoma (HCC) patients with high tumor mutational burden (TMB) >10 mutations/megabase. Patients received camrelizumab + lenvatinib (n=168) or sorafenib (n=168).

Median follow-up was 18.3 months. Camrelizumab + lenvatinib significantly improved overall survival (OS) (median 20.6 vs 13.8 months; HR=0.62; p=0.0008) and progression-free survival (PFS) (median 7.5 vs 4.3 months; HR=0.54; p<0.0001) versus sorafenib.

ORR was 37.5% vs 12.5% (p<0.001). Grade 3 or higher adverse events occurred in 57.1% and 50.0% of patients, respectively. Safety profiles were consistent with previous studies.