AZD7789 for Cancer

Recruiting at 27 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Must be taking: Anti-PD-1/PD-L1

Must not be taking: Immunosuppressive, Anti-TIM-3

Disqualifiers: EGFR mutations, ALK fusions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

136 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD7789, an experimental drug under study for its safety and effectiveness in treating advanced solid tumors. It targets patients with advanced non-small cell lung cancer (NSCLC) and certain types of stomach cancer unsuitable for surgery or radiation. The trial divides participants into groups to evaluate the drug's effectiveness across different cancer backgrounds and treatment histories. Individuals diagnosed with advanced NSCLC or gastric cancer, who cannot undergo surgery or radiation and may have tried other treatments, could be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use immunosuppressive medication within 14 days before starting the study. Also, you cannot have any concurrent cancer treatments like chemotherapy or radiotherapy while participating.

Is there any evidence suggesting that AZD7789 is likely to be safe for humans?

Research has shown that AZD7789 is generally well-tolerated. In earlier studies, patients experienced no severe side effects from the treatment at the tested doses, indicating no significant harm at those levels. Only one serious side effect was reported, but it was not directly linked to the treatment. Overall, AZD7789 appears safe and manageable, particularly for individuals with advanced solid tumors such as non-small cell lung cancer (NSCLC). Safety checks continue to ensure these results remain consistent for a broader population. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

Researchers are excited about AZD7789 because it offers a new approach to treating certain cancers, particularly non-small cell lung cancer (NSCLC) and advanced gastric cancers. Unlike the standard treatments, which often involve chemotherapy or immunotherapy, AZD7789 is a monotherapy that targets specific proteins involved in cancer cell growth, potentially leading to more effective results. This treatment's unique mechanism of action may offer new hope for patients who have developed resistance to existing therapies, providing an alternative that could enhance their response to treatment.

What evidence suggests that AZD7789 might be an effective treatment for advanced solid tumors?

Research has shown that AZD7789, a special type of antibody, may help treat non-small cell lung cancer (NSCLC). In earlier studies, 10% of patients with advanced NSCLC, who had already tried other treatments, saw their tumors shrink, although the tumors did not completely disappear. This trial tests AZD7789 in various treatment arms for different cancer types, including NSCLC and stomach and gastroesophageal junction cancer, to evaluate its safety and effectiveness. Overall, AZD7789 is under study for its potential to boost the body's immune system to fight cancer cells. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

Adults with advanced or metastatic solid tumors, such as non-small cell lung cancer or stomach cancers, who have had prior treatments but not in the first-line setting. Participants must be able to provide a tumor tissue sample and meet certain health criteria like good organ function and performance status.

Inclusion Criteria

Your PD-L1 expression level is less than 1% or equal to or more than 1%.

I have had treatment before that included anti-PD-1/PD-L1 therapy.

My lung cancer is at an advanced stage and cannot be cured with surgery or radiation.

Exclusion Criteria

My non-small cell lung cancer has specific genetic changes (EGFR mutations or ALK fusions).

My cancer has HER2 amplification and I haven't received standard HER2 therapy.

I have had a blood clot or heart attack in the last 6 months but am stable on medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive AZD7789 monotherapy in dose escalation cohorts to determine the maximum tolerated dose

18 months

Dose Expansion

Participants receive AZD7789 monotherapy in dose expansion cohorts to further evaluate safety and efficacy

4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days post last dose

What Are the Treatments Tested in This Trial?

Interventions

• AZD7789

Trial Overview The trial is testing AZD7789, an experimental drug targeting PD-1 and TIM-3 pathways in cancer cells. It's for patients whose cancers haven't responded well to standard treatments. The study will check if this new treatment is safe and effective.

How Is the Trial Designed?

Group I: Dose Expansion Part B5: NSCLC IO naive, PD-L1 1-49% - RP2D Level 1 Experimental Treatment 1 Intervention

AZD7789 monotherapy

Group II: Dose Expansion Part B4: advanced or metastatic gastric and GEJC IO acquired resistance- RP2D level 1 Experimental Treatment 1 Intervention

AZD7789 monotherapy

Group III: Dose Expansion Part B3: NSCLC IO acquired resistance - RP2D level 2 Experimental Treatment 1 Intervention

AZD7789 Monotherapy

Group IV: Dose Expansion Part B2: NSCLC IO naive, PD-L1 50% or greater - RP2D level 1 Experimental Treatment 1 Intervention

AZD7789 Monotherapy

Group V: Dose Expansion Part B1: NSCLC IO acquired resistance - RP2D level 1 Experimental Treatment 1 Intervention

AZD7789 Monotherapy

Group VI: Dose Escalation Part A: NSCLC Immuno-oncology (IO) acquired or primary resistance Experimental Treatment 1 Intervention

AZD7789 monotherapy

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

ZD1839 effectively inhibits the growth of breast cancer cells that overexpress both EGFR and HER2, demonstrating its potential as a treatment for these types of tumors.

The mechanism of action involves ZD1839 inducing the formation of inactive receptor complexes (heterodimers) between EGFR and HER2/HER3, which prevents their activation and downstream signaling, suggesting a novel approach to targeting HER2 in breast cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ZD1839, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in HER2-overexpressing breast cancer cells. Anido, J., Matar, P., Albanell, J., et al.[2022]

AZD1775, a WEE1 kinase inhibitor, was found to be safe and well-tolerated in a study involving 202 patients with refractory solid tumors, both as a monotherapy and in combination with chemotherapy.

The study showed that AZD1775 effectively engaged its target, leading to a 21% response rate in TP53-mutated patients, compared to 12% in those with wild-type TP53, suggesting it may be particularly beneficial for patients with TP53 deficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study Evaluating WEE1 Inhibitor AZD1775 As Monotherapy and in Combination With Gemcitabine, Cisplatin, or Carboplatin in Patients With Advanced Solid Tumors. Leijen, S., van Geel, RM., Pavlick, AC., et al.[2023]

AZD2171, a potent inhibitor of vascular endothelial growth factor receptors, can be safely combined with standard chemotherapy (carboplatin and paclitaxel) in patients with advanced non-small-cell lung cancer, showing no dose-limiting toxicities at doses of 30 mg or 45 mg per day.

The combination treatment resulted in a 45% response rate, with tumor shrinkage observed in nearly all patients, indicating promising antitumor activity despite some manageable side effects like fatigue and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group. Laurie, SA., Gauthier, I., Arnold, A., et al.[2015]

AZD2171, a potent inhibitor of vascular endothelial growth factor receptor signaling, significantly enhances the antitumor effects of radiotherapy in lung and colon tumor models, leading to greater growth delay compared to either treatment alone.

The combination treatment not only reduced tumor vessel density and perfusion but also increased tumor hypoxia, suggesting that AZD2171 sensitizes tumors to radiotherapy, supporting its potential for clinical use alongside radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit. Williams, KJ., Telfer, BA., Shannon, AM., et al.[2022]

In a study of 32 patients with non-small-cell lung cancer (NSCLC) treated with ZD1839 for over 90 days, the drug achieved a disease control rate of 56.25%, with 18.75% experiencing partial remission.

ZD1839 was associated with manageable side effects, including acneiform rash (31.25%) and diarrhea (18.75%), but notably did not cause interstitial lung disease, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical observation of ZD1839 in treating 32 cases of non-small-cell lung cancer]. Zhang, L.[2018]

The recommended phase II dose (RP2D) of AZD8931 combined with chemotherapy (Xelox) was determined to be 20 mg twice daily, showing an acceptable safety profile despite some dose-limiting toxicities observed in 24 patients, including skin rash and severe gastrointestinal side effects.

In the expansion phase, the combination of Xelox and AZD8931 resulted in a lower complete resection rate (45%) compared to Xelox alone (90%), and while the six-month progression-free survival was 85% for the combination group, it was 100% for the Xelox-only group, indicating that AZD8931 may not enhance surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual Erb B Inhibition in Oesophago-gastric Cancer (DEBIOC): A phase I dose escalating safety study and randomised dose expansion of AZD8931 in combination with oxaliplatin and capecitabine chemotherapy in patients with oesophagogastric adenocarcinoma. Thomas, A., Virdee, PS., Eatock, M., et al.[2023]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03184-8/fulltext

1313MO Safety and preliminary efficacy of AZD7789, a ... Here we report dose escalation results from a phase 1/2a, first-in-human, multicentre, open-label trial of AZD7789 monotherapy in pts with stage IIIB–IV NSCLC ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04931654

NCT04931654 | A Study to Assess the Safety and Efficacy ... This is a Phase I/IIa study designed to evaluate if experimental anti-PD-1 and anti-TIM-3 bispecific antibody, AZD7789 is safe, tolerable and efficacious in ...

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9570C00001

A study to assess the safety and efficacy of AZD7789 ... This is a Phase I/IIa study designed to evaluate if experimental anti-PD-1 and anti-TIM-3 bispecific antibody, AZD7789 is safe, tolerable and efficacious in ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-azd7789-for-patients-with-advanced-or-metastatic-solid-tumors-including-non-small-cell-lung-cancer-and-gastric-cancer/

Study on the Safety and Effectiveness of AZD7789 ... This study investigates the safety and efficacy of AZD7789, a targeted treatment for patients with advanced or metastatic solid tumors, ...

5. researchgate.net researchgate.net/publication/374883961_1313MO_Safety_and_preliminary_efficacy_of_AZD7789_a_bispecific_antibody_targeting_PD-1_and_TIM-3_in_patients_pts_with_stage_IIIB-IV_non-small-cell_lung_cancer_NSCLC_with_previous_anti-PD-L1_therapy

1313MO Safety and preliminary efficacy of AZD7789, a ... AZD7789 demonstrated an unconfirmed partial response rate of 10% in stage IIIB-IV non-small cell lung cancer (NSCLC) patients who had previously received anti- ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/4433/503389/Safety-and-Preliminary-Efficacy-of-Sabestomig

Safety and Preliminary Efficacy of Sabestomig (AZD7789), an ... Sabestomig was well tolerated with no Grade ≥3 treatment-related adverse events (AEs) (Table 2). One Grade ≥3 AE occurred, which was fatal ( ...