Novel Anti-Cancer Agents for Non-Small Cell Lung Cancer

(HUDSON Trial)

Recruiting at 41 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Chemotherapy, Immunotherapy, Biologics, Hormonal

Disqualifiers: EGFR, ALK, Autoimmune, Infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

527 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing several new treatments for advanced lung cancer in patients who haven't responded to standard therapies. It aims to find out which new treatments are effective and safe.

Will I have to stop taking my current medications?

The trial requires that you stop any current chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. However, you can continue treatment with bisphosphonates or RANKL inhibitors for bone metastases.

How is the drug AZD6738, AZD9150, Cediranib, Durvalumab, Olaparib, Oleclumab, Trastuzumab Deruxtecan, Vistusertib different from other drugs for non-small cell lung cancer?

This drug combination is unique because it includes a mix of targeted therapies and immunotherapies, such as Durvalumab (an immune checkpoint inhibitor) and Olaparib (a PARP inhibitor), which work by enhancing the body's immune response and targeting specific cancer cell mechanisms, offering a novel approach compared to traditional chemotherapy. ^{1 2 3 4 5}

Research Team

John Heymach, M.D, Ph.D

Principal Investigator

The University of Texas MD Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced NSCLC who've had disease progression after anti-PD-1/PD-L1 therapy and platinum-doublet chemotherapy. They should be in good physical condition, not pregnant or breastfeeding, willing to use birth control, and have no severe allergies to study drugs or history of certain immune disorders.

Inclusion Criteria

I have at least one tumor that can be measured, including any that have grown after radiation.

My NSCLC is getting worse and has spread or come back.

I've had NSCLC treatment with antiPD1/PD-L1 and platinum drugs but my cancer progressed.

Exclusion Criteria

My cancer does not have specific genetic changes in EGFR, ALK, ROS1, BRAF, MET, or RET.

I am not pregnant, breastfeeding, and if capable of having children, I agree to use birth control.

I am not on any cancer treatments except for bone metastases management.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various combinations of durvalumab and other agents such as AZD6738, olaparib, and others, in a modular design to assess efficacy, safety, and tolerability.

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of tumour size, duration of response, and adverse events.

Up to 3.5 years

Long-term follow-up

Participants are monitored for overall survival and long-term safety outcomes.

Up to 4.5 years

Treatment Details

Interventions

• AZD6738
• AZD9150
• Cediranib
• Durvalumab
• Olaparib
• Oleclumab
• Trastuzumab Deruxtecan
• Vistusertib

Trial Overview The trial tests multiple treatments like trastuzumab deruxtecan, cediranib, and others on patients with metastatic NSCLC post anti-PD-1/PD-L1 therapy failure. It's an open-label Phase II study assessing the efficacy and safety of these novel agents.

Participant Groups

Group I: durvalumab + trastuzumab deruxtecan Experimental Treatment 1 Intervention

durvalumab given in combination with trastuzumab deruxtecan (DS-8201a)

Group II: durvalumab + cediranib Experimental Treatment 2 Interventions

durvalumab given in combination with cediranib (AZD2171)

Group III: durvalumab & AZD6738 (ceralasertib) (240 mg or 160 mg) Experimental Treatment 1 Intervention

durvalumab in combination with twice daily 160 mg or 240 mg AZD6738 (D22-D28)

Group IV: durvalumab & AZD6738 (ceralasertib) Experimental Treatment 2 Interventions

durvalumab given in combination with AZD6738 (D15-D28)

Group V: Durvalumab + vistusertib Experimental Treatment 2 Interventions

Durvalumab given in combination with Vistusertib (AZD2014).

Group VI: Durvalumab + olaparib Experimental Treatment 2 Interventions

Durvalumab given in combination with olaparib .

Group VII: Durvalumab + Oleclumab Experimental Treatment 2 Interventions

Durvalumab given in combination with Oleclumab

Group VIII: Durvalumab + AZD9150 Experimental Treatment 2 Interventions

Durvalumab given in combination with AZD9150.

Group IX: Durvalumab + AZD6738 Experimental Treatment 2 Interventions

Durvalumab given in combination with AZD6738.

Group X: AZD6738 (ceralasertib) monotherapy Experimental Treatment 1 Intervention

AZD6738 (ceralasertib) given as monotherapy

Group XI: AZD6738 (ceralasertib) 7 days monotherapy Experimental Treatment 1 Intervention

AZD6738 (ceralasertib) monotherapy on D1-7 of every 28 days

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

Over the past two decades, the addition of cisplatin-based regimens has led to modest improvements in chemotherapy for non-small cell lung cancer, with several new agents like navelbine and taxanes showing significant activity in Phase II and III testing.

Future treatments may involve combining these new drugs with targeted therapies that specifically attack unique characteristics of non-small cell lung cancer cells, potentially enhancing efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New chemotherapy agents in the treatment of advanced non-small cell lung cancer: an update including data from the Seventh World Conference on Lung Cancer. Comis, RL., Friedland, DM.[2019]

Current standard treatment for advanced non-small-cell lung cancer involves doublet chemotherapy, which has shown 1-year survival rates of approximately 35% and 2-year survival rates of about 15%.

Preliminary studies indicate that triplet therapy may enhance survival rates compared to double therapy, with toxicity rates being low enough to support the development of these three-drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination chemotherapy and targeted therapy regimens. Bunn, PA.[2005]

Only a few traditional chemotherapeutic agents have shown single-agent response rates greater than 15% in treating non-small-cell lung cancer (NSCLC), indicating limited effectiveness with standard treatments.

Recent phase I/II trials have identified new drugs, such as navelbine, CTP-11, topotecan, and taxol, that have achieved single-agent response rates above 20%, suggesting improved treatment options for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New directions for chemotherapy in non-small-cell lung cancer. Green, MR.[2019]

References

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

Gefitinib: phase II and III results in advanced non-small cell lung cancer. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Gefitinib (Iressa): a novel treatment for non-small cell lung cancer. [2018]

3. Ireland pubmed.ncbi.nlm.nih.gov

New chemotherapy agents in the treatment of advanced non-small cell lung cancer: an update including data from the Seventh World Conference on Lung Cancer. [2019]

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

Triplet combination chemotherapy and targeted therapy regimens. [2005]

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

New directions for chemotherapy in non-small-cell lung cancer. [2019]