AZD7789 for Cancer

Recruiting at 22 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

Trial Summary

What is the purpose of this trial?

This trial is testing a new medicine called AZD7789 that helps the immune system fight advanced solid tumors by blocking proteins that hide cancer cells. It aims to see if the medicine is safe and effective for patients whose cancer has progressed despite other treatments.

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.

What data supports the effectiveness of the drug AZD7789 for cancer?

Research on a similar drug, AZD2171, shows it can enhance the effects of chemotherapy and radiotherapy in lung and colon cancer models by reducing blood vessel growth in tumors, which may suggest potential effectiveness for AZD7789 in cancer treatment. ^{1 2 3 4 5}

How does the drug AZD7789 differ from other cancer treatments?

AZD7789 is unique because it may combine the mechanisms of action from drugs like ZD1839, which inhibits the epidermal growth factor receptor (EGFR) to block cancer cell growth, and AZD1775, which targets the WEE1 kinase to make cancer cells more sensitive to DNA damage. This dual approach could potentially offer a novel way to treat cancers that are resistant to standard therapies. ^{6 7 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. United States 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. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit. [2022]

3. England 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Osimertinib Regresses an EGFR-Mutant Cisplatinum- Resistant Lung Adenocarcinoma Growing in the Brain in Nude Mice. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Studies with ZD1839 in preclinical models. [2018]

7. China pubmed.ncbi.nlm.nih.gov

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

8. United States pubmed.ncbi.nlm.nih.gov

Phase I studies of ZD1839 in patients with common solid tumors. [2018]

9. United States 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. [2022]

10. United States 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. [2023]