A Phase I/II Open-label Dose Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD6750, a CD8 Guided IL-2 Agent Alone and in Combination With Other Anti-cancer Agents in Participants With Select Advanced or Metastatic Solid Tumors

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Overview

Rilvegostomig (AZD2936) is an investigational bispecific monoclonal antibody from AstraZeneca that targets PD‑1 and TIGIT. It is being studied across multiple tumor types, with ongoing phase 3 programs including first‑line metastatic non‑squamous NSCLC (ARTEMIDE‑Lung03), adjuvant biliary tract cancer after resection (ARTEMIDE‑Biliary01), first‑line advanced hepatocellular carcinoma (ARTEMIDE‑HCC01), and first‑line HER2‑positive, PD‑L1–positive gastric/GEJ cancer (ARTEMIDE‑Gastric01). (cdek.pharmacy.purdue.edu)

Mechanism of action

• Bispecific IgG1 engineered to bind PD‑1 and TIGIT on the same T cell, aiming to augment antitumor immunity beyond PD‑1 blockade alone. The Fc region carries triple mutations (L234F/L235E/P331S) to reduce Fc‑mediated effector function. (cdek.pharmacy.purdue.edu)
• Constructed on a DuetMab backbone; the TIGIT arm derives from Compugen’s anti‑TIGIT antibody (COM902). (cdek.pharmacy.purdue.edu)
• Early clinical and translational work suggests high receptor occupancy on peripheral T cells at clinically relevant doses. (pmc.ncbi.nlm.nih.gov)

Efficacy

NSCLC (ARTEMIDE‑01, Phase I/II)

• CPI‑pretreated cohort (dose escalation/expansion; PD‑L1 TPS ≥1%): among 83 patients, confirmed ORR 4.8% (all partial responses); median PFS 2.1 months (95% CI 2.0–4.1); 27‑week DCR 31.3%. Recommended phase 2 dose (RP2D) 750 mg Q3W. (oncologypro.esmo.org)
• CPI‑naïve cohorts:
• PD‑L1 TPS 1–49%: ORR 29%; median PFS 6.0 months (95% CI 2.7–8.4); median DOR 6.4 months (95% CI 4.2–NC). (onclive.com)
• PD‑L1 TPS ≥50%: ORR 61.8% (95% CI 43.6–77.8%); median PFS 10.2 months (95% CI 6.3–NC); median DOR 10.3 months (95% CI 8.2–NC). Data are from the first analysis of ARTEMIDE‑01 CPI‑naïve parts C/D and remain preliminary. (onclive.com)

Ongoing phase 3 studies (no efficacy readouts yet)

• NSCLC: ARTEMIDE‑Lung03 compares rilvegostomig + platinum/pemetrexed vs pembrolizumab + platinum/pemetrexed in first‑line PD‑L1–positive metastatic non‑squamous NSCLC (started November 2024; target n≈878). (cdek.pharmacy.purdue.edu)
• Biliary tract cancer (adjuvant): ARTEMIDE‑Biliary01 evaluates rilvegostomig + investigator’s‑choice chemotherapy (capecitabine, S‑1, or gemcitabine/cisplatin) vs placebo + chemotherapy; primary endpoint recurrence‑free survival (JCO abstract TPS4199; enrollment began 2024; planned n≈750). (ascopubs.org)
• Hepatocellular carcinoma: ARTEMIDE‑HCC01 compares rilvegostomig + bevacizumab with or without tremelimumab vs atezolizumab + bevacizumab in first‑line advanced HCC (registered as NCT06921785; launched 2025; planned n≈1220). (smartpatients.com)
• Gastric/GEJ (HER2+, PD‑L1 CPS ≥1): ARTEMIDE‑Gastric01 (phase 3) tests rilvegostomig + fluoropyrimidine + trastuzumab deruxtecan vs trastuzumab + chemotherapy + pembrolizumab (3‑arm design; recruiting). (cdek.pharmacy.purdue.edu)

Safety

• CPI‑pretreated NSCLC (ARTEMIDE‑01 parts A/B): treatment‑related AEs in 54.2% (grade ≥3 in 8.4%); no grade 4/5 treatment‑related AEs; discontinuations 3.6%. (oncologypro.esmo.org)
• CPI‑naïve NSCLC (ARTEMIDE‑01 parts C/D): grade ≥3 treatment‑related AEs 10.5%; treatment‑related discontinuations 4.2%; no clear safety differences between 750 mg and 1500 mg Q3W. (onclive.com)

Key trials (selection)

• Phase I/II first‑in‑human NSCLC: ARTEMIDE‑01 (NCT04995523). (cdek.pharmacy.purdue.edu)
• Phase III first‑line NSCLC: ARTEMIDE‑Lung03 (NCT06627647). (cdek.pharmacy.purdue.edu)
• Phase III adjuvant BTC: ARTEMIDE‑Biliary01 (NCT06109779). (ascopubs.org)
• Phase III first‑line HCC: ARTEMIDE‑HCC01 (NCT06921785). (smartpatients.com)
• Phase III first‑line HER2+ gastric/GEJ: ARTEMIDE‑Gastric01 (NCT06764875). (cdek.pharmacy.purdue.edu)

Further reading

• Preliminary efficacy/safety in CPI‑pretreated NSCLC (ESMO 2023 abstract 1446P). (oncologypro.esmo.org)
• CPI‑naïve NSCLC first analysis (IASLC WCLC 2024; JTO abstract OA11.03) and summary news. (jto.org)
• ARTEMIDE‑Biliary01 phase 3 study design (JCO TPS4199). (ascopubs.org)
• ARTEMIDE‑Lung03 phase 3 NSCLC listing. (cdek.pharmacy.purdue.edu)
• ARTEMIDE‑HCC01 trial registration (NCT06921785). (anzctr.org.au)
• Mechanistic and development context (FDA UNII; review articles with trial summaries). (precision.fda.gov)

Notes: Human efficacy data to date are from phase I/II NSCLC cohorts; phase 3 trials listed above are ongoing without reported outcomes as of October 7, 2025. (cdek.pharmacy.purdue.edu)

Last updated: Oct 2025

Overview

AZD6750 is an investigational, intravenously administered CD8‑guided interleukin‑2 (IL‑2) agent being developed by AstraZeneca for advanced or metastatic solid tumors. A first-in-human, multicenter phase 1/2 dose‑escalation and expansion trial (NCT07115043; study D7350C00001) began on July 29, 2025, and is recruiting across the United States, Australia, and Japan. The study evaluates AZD6750 as monotherapy and in combination with rilvegostomig, a PD‑1/TIGIT bispecific antibody. As of October 7, 2025, no efficacy or safety results in humans have been reported. (ichgcp.net)

Mechanism of action

AZD6750 is described as a “CD8‑guided IL‑2” construct: an antibody that specifically binds human CD8 fused to an IL‑2 cytokine domain. The intended design is to preferentially deliver IL‑2 signaling to CD8+ T cells, enhancing effector T‑cell activity while limiting stimulation of regulatory T cells and off‑target tissues associated with conventional IL‑2 toxicities. This design is supported by AstraZeneca’s 2025 international patent application on CD8‑binding cytokine engagers. The phase 1/2 trial listings also describe AZD6750 as a CD8‑guided IL‑2. (ipqwery.com)

For the planned combination arm, rilvegostomig provides dual PD‑1/TIGIT checkpoint blockade; the agent is in late‑stage development in other settings. Preclinical and translational literature supports the biological rationale that IL‑2 signaling can synergize with PD‑1 pathway blockade by reprogramming stem‑like/exhausted CD8+ T cells toward functional effectors, although this evidence is not specific to AZD6750. (prnewswire.com)

Efficacy

• No human efficacy data for AZD6750 have been released. The ongoing phase 1/2 study will assess preliminary antitumor activity in selected solid tumors (including melanoma, RCC, TNBC, NSCLC, HNSCC, gastric/GEJ, SCC of skin, Merkel cell carcinoma, and high‑grade serous ovarian carcinoma). (ichgcp.net)

Safety

• No human safety data for AZD6750 have been reported as of this date. The current trial’s primary objectives include safety, tolerability, and dose finding for monotherapy and for combination with rilvegostomig. (ichgcp.net)

Key trial

• NCT07115043 (D7350C00001): Phase 1/2, open‑label, dose‑escalation/expansion of AZD6750 alone and with rilvegostomig in adults with select advanced/metastatic solid tumors; target enrollment ~60; study start July 29, 2025; estimated primary completion April 9, 2029. Sites in the United States, Australia, and Japan; recruiting. (ichgcp.net)

Further reading

• AstraZeneca study page for D7350C00001 (mechanism noted as “CD8‑guided IL‑2” and trial details). (astrazenecaclinicaltrials.com)
• ANZCTR record for the Australian arm of NCT07115043. (anzctr.org.au)
• ICH‑GCP/clinical‑trials registry mirrors for NCT07115043 (study synopsis and sites). (ichgcp.net)
• Patent: CD8‑binding cytokine engagers (antibody fused to cytokine such as IL‑2) filed by AstraZeneca in 2025. (ipqwery.com)
• Background on PD‑1/TIGIT bispecific rilvegostomig (for combination context). (prnewswire.com)
• Mechanistic rationale: IL‑2 plus PD‑1 blockade modifies exhausted CD8+ T‑cell programs (non‑AZD6750 specific). (pubmed.ncbi.nlm.nih.gov)

Note: Because AZD6750 entered first‑in‑human testing in July 2025, peer‑reviewed clinical results are not yet available; updates should be monitored through the trial registry and future conference abstracts or publications. (ichgcp.net)

Last updated: Oct 2025

Inclusion criteria:

* Participant ≥ 18 year

* ECOG PS of 0 to 1

* Provision of 'archival' tumor specimen

* At least one measurable lesion according to RECIST v1.1,

* Minimum life expectancy of 12 weeks

* Adequate and stable cardiac function

* Adequate bone marrow, liver and kidney function

* Body weight ≥ 35 kg

* Capable of giving signed informed consent

Module 1 specific inclusion criteria:

• Participants with locally advanced or metastatic select solid tumors (MM, Squamous cell carcinoma of skin, MCC, NSCLC, Head and neck squamous cell carcinoma, Gastric cancer/gastroesophaegeal junction cancer, RCC, HGSOC, Triple negative breast cancer) who have received adequate SoC

Module 2 specific inclusion criteria:

* Participants with Stage IV NSCLC Dose Escalation/Backfills

1. Have received at least one prior regimen in metastatic setting (2L+ NSCLC). Participants with actionable tumor alterations should have received targeted therapy if locally available OR

2. Have not received systemic therapy (1L NSCLC) and have PD-L1 expression ≥ 1%.

Dose Expansion

1. Have not received systemic therapy (1L NSCLC) and have PD-L1 expression ≥ 1%.

Exclusion criteria:

* Any evidence of:

Severe or uncontrolled systemic diseases including respiratory, cardiac or tumor-related conditions

* History or planned organ or allogeneic stem cell transplantation.

* Active or prior documented autoimmune or inflammatory disorders, within the past 3 years

* Any prior toxicities that led to permanent discontinuation of prior immunotherapy

* Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anti-cancer therapy

* Brain metastases unless treated, asymptomatic, stable, and not requiring continuous corticosteroids

* Acute untreated or symptomatic malignant spinal cord compression, or a history of leptomeningeal carcinomatosis.

* Active uncontrolled or chronic infection of hepatitis B, hepatitis C

* Prior history of Grade ≥ 3 non-infectious pneumonitis.

* Participant requires chronic immunosuppressive therapy (including steroids \> 10 mg prednisone/day or equivalent).

* Receipt of live attenuated vaccine within 30 days.

Module 2 specific exclusion criteria:

* Previous treatment with anti-TIGIT therapy

* 1L NSCLC participants with genetic alteration such as EGFR that has a targeted therapy in 1L as per local SoC