AstraZeneca Presents Promising Clinical Data for PD-1×TIGIT Bispecific Rilvegostomig and CD19×CD3 Bispecific AZD0486 at ASCO 2025

The 2025 ASCO Conference is currently underway. At this year's conference, AstraZeneca has released over 80 abstracts, including research on several investigational new drugs. Bispecific antibodies, as a key focus of AstraZeneca’s R&D pipeline, are also featured in multiple studies. This article will share insights on Rilvegostomig.(PD-1×TIGIT bispecific antibody)、AZD0486(CD19×CD3 Bispecific Antibody)Data from three studies.

Insight data shows that AstraZeneca has no bispecific antibody drugs approved for marketing yet. Rilvegostomig and AZD0486, two drugs currently in Phase III trials, are expected to become the first wave of bispecific antibody drugs to be marketed by AstraZeneca.

Treatment Drug: Rilvegostomig + Chemotherapy

Indications: Advanced Biliary Tract Cancer

Abstract Number: 4080

Rilvegostomig(hereinafter referred to as Rilve)It is a PD-1×TIGIT bispecific antibody under development by AstraZeneca., currently in Phase III clinical trials, ranks 1st in the PD-1×TIGIT bispecific antibody track.

The II Phase Clinical Trial Codenamed GEMINI-Hepatobiliary Was Announced at This Conference(NCT05775159) Preliminary analysis results of Cohort A from Sub-study 2. The GEMINI-Hepatobiliary study aims to evaluate Rilve or Volrustomig as monotherapy or in combination regimens for advanced hepatocellular carcinoma.(Sub-study 1)Or patients with advanced biliary tract cancer(Sub-study 2)Efficacy in China.

Screenshot source: ASCO official website

In Sub-study 2 Cohort A, a total of 30 patients with advanced biliary tract cancer received treatment. As of November 4, 2024, the median follow-up time for all patients was 6.9 months, and 36.7% of the patients were still receiving Rilve treatment. The preliminary analysis results show:

• 6-Month Progression-Free Survival（PFS）The rate was 73.0%; the median PFS was 8.3 months.. PD-L1 Tumor Area Positive (TAP) Median PFS in Patients with a Score ≥1%(9.4 months, n = 18)Significantly longer than the overall study population.

• Safety is controllable, consistent with previous studies. The exposure of Rilve is consistent with historical monotherapy data, indicating no PK drug interaction and no cross-indication differences. Rilve achieves ≥90% receptor occupancy of PD-1 and TIGIT on peripheral T cells in subjects.（RO）, and induce the proliferation of peripheral T cells.

Screenshot source: Insight database

Overall, Rilve combined with chemotherapy demonstrated good efficacy and a manageable safety profile. Longer follow-up is needed to ensure data maturity. Currently,Rilve Phase III Clinical Trial for Biliary Tract Cancer(ARTEMIDE-Biliary 01；DESTINY-BTC01) In Progress。

Treatment Drugs: Rilvegostomig+Dato-DXd

Indications: First-line treatment for advanced or metastatic non-small cell lung cancer

Abstract Number: 8521

AstraZeneca also announced Rilvegostomig and Dato-DXd at this year's conference.（TROP2 ADC）Phase 1b, Open-Label, Dose-Escalation and Expansion Study of Combination Therapy TROPION-Lung04 (NCT04612751) Data results from Cohort 5, which enrolled patients without anti-cancer genes. (AGA) TheAdvanced or Metastatic NSCLCPatient.

Screenshot source: ASCO official website

In Cohort 5, treatment-naïve patients received Dato-DXd(6 mg/kg) + Rilvegostomig intravenous injection, once every three weeks. Patients continue treatment until disease progression or unacceptable toxicity occurs. The primary endpoint is safety. Secondary endpoints include the objective response rate assessed by investigators. (ORR), Duration of Relief (DoR)and Progression-Free Survival (PFS)。

As of October 24, 2024, 40 patients received Dato-DXd + Rilvegostomig treatment; 29 patients had non-squamous histology. The median treatment duration was 5.1 months; 21 patients discontinued Dato-DXd, and 20 patients discontinued Rilvegostomig.（50.0%）The patient was still receiving treatment at the data cut-off date.

Efficacy data shows,The confirmed ORR for all patients was 57.5%, with a disease control rate of 95.0%.. Squamous Cell Carcinoma（ORR 45.5%）And non-squamous cell carcinoma（ORR 62.1%）Responses were observed in all patients with PD-L1 expression. As of the data cutoff date, DoR and PFS were not yet mature.

All patients experienced adverse events during treatment.（TEAE）, 60.0% of patients experienced ≥3 grade TEAEs, and 50.0% of patients experienced serious TEAEs. The most common TEAEs included stomatitis, fatigue, alopecia, and nausea. Ocular surface events occurred in 12 patients. Five patients reported adjudicated drug-related interstitial lung disease/pneumonia. Six fatal TEAEs occurred.，But none of them are related to the treatment drugs.

Screenshot source: Insight database

In summary, the study concluded that the safety of the combination therapy with these two drugs is consistent with the expected toxicity profiles of each drug, and no new safety findings were identified. Dato-DXd + RilvegostomigAs a first-line treatment for patients with advanced or metastatic NSCLC without AGA, it has shown encouraging activity, with responses observed across both histologies and all PD-L1 levels.。

Treatment regimen: AZD0486

Indications: Diffuse Large B-Cell Lymphoma

Abstract Number: 7046

AZD0486 is a novel IgG4 fully human CD19xCD3 bispecific T-cell engager developed by AstraZeneca. It is currently in Phase III clinical trials.The Second Fastest CD19xCD3 Bispecific Antibody Globally.

The study presented at this conference is an ongoing trial targeting relapsed/refractory（R/R）Diffuse Large B-Cell Lymphoma（DLBCL）Phase Ⅰ Clinical Trial of the Patient（NCT04594642）The main purpose of the study is to evaluate safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose. (MTD)。

Screenshot source: ASCO official website

As of September 29, 2024, 70 patients with R/R DLBCL received AZD0486 treatment at target doses of ≤0.8 mg, 2.4 mg, 7.2 mg, 15 mg, and 25 mg, respectively. The median number of treatment lines was 3, with 34 cases.（49%）The patient had previously received CD19-targeted CAR-T therapy.

Among 61 evaluable patients with TDs≥2.4 mg,ORR and CR rates were 46% and 33%, respectively.. The higher the dose, the higher the ORR/CR rate.(39%/22% in the 2.4 mg group, 43%/33% in the 7.2 mg group, and 55%/41% in the 15 mg group)。The ORR/CR rate for patients who have not received CAR-T therapy was 57%/39%, higher than that for patients who have received CAR-T therapy.（36%/27%）。

Patients receiving 7.2 mg or 15 mg treatment(Median follow-up times were 8.8 months and 5.3 months, respectively)`, Median Duration of Response`（DOR）Not reached;Estimated 12-Month DOR: 64%. One patient who achieved CR experienced disease progression. Among 15 evaluable patients who achieved CR in the 7.2 mg and 15 mg treatment groups, 87% did not meet MRD criteria.

Screenshot source: Insight database

In terms of safety, in the overall population, 37% of patients experienced infections, of which 9% were ≥G3 grade infections; 13% of patients were infected with COVID-19. Febrile neutropenia occurred in 3% of patients. ≥G3 grade neutropenia occurred in 23% of patients, and ≥G3 grade anemia occurred in 14% of patients.

In summary, the study concluded that AZD0486 at doses of TDs ≥2.4 mg is effective for relapsed/refractory DLBCLThe patient showed good efficacy and controllable safety. Target doses up to 25 mg have been tested without exceeding the maximum tolerated dose. The dose is being continuously increased.

For more information on AstraZeneca's disclosed research data at this year’s ASCO, you can scan the QR code below.Insight Database "Clinical Trial Results Module"Proceed to view.

Cover Source:Insight Database Chart

Disclaimer:This article is for information sharing only, and does not represent the position or viewpoint of Insight. It does not recommend or introduce any treatment plans. If necessary, please consult and contact正规医疗机构.

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