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

(HUDSON Trial)

Not currently recruiting at 47 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals with non-small cell lung cancer that has spread and continues to grow despite previous treatment. It evaluates the effectiveness, safety, and tolerability of different drug combinations. Participants will receive various combinations of medications, including durvalumab (an immunotherapy drug), tailored to their specific cancer traits. This trial may suit those whose lung cancer has worsened after certain prior therapies and who have a measurable tumor. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, providing early access to potentially effective therapies.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found durvalumab to be safe and tolerable for patients with advanced non-small cell lung cancer (NSCLC). Used alone, it led to lasting positive responses with manageable side effects. Research has shown that olaparib can extend the time patients live without their disease worsening, with generally manageable side effects.

Research on combining danvatirsen with durvalumab showed it was well tolerated, with no new safety issues. Ceralasertib, when used with durvalumab, has shown promising safety results, and some studies suggest it enhances treatment effectiveness in NSCLC.

Cediranib, a drug that blocks certain enzymes to stop cancer growth, has been well tolerated when combined with other treatments in NSCLC, showing promising results. Oleclumab, when combined with durvalumab, showed limited overall activity but was generally well tolerated in early studies.

Trastuzumab deruxtecan, used for HER2-mutant NSCLC, has been associated with common side effects like a decrease in white blood cell count, but it has shown lasting anticancer effects. Lastly, vistusertib, a drug that blocks certain proteins to prevent cancer growth, has been studied for lung cancer and showed a promising safety profile when used with other treatments.

This trial is in Phase 2, focusing on how well the treatment works while monitoring safety. This phase indicates that earlier safety tests were positive enough to proceed with further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they target specific genetic mutations and molecular pathways, offering a more personalized approach than traditional chemotherapy. For example, durvalumab, an immunotherapy drug, is combined with various agents like olaparib, which blocks a DNA repair enzyme called PARP, and trastuzumab deruxtecan, which targets HER2 mutations. Additionally, oleclumab targets CD73 to enhance immune response, and ceralasertib, an ATR inhibitor, disrupts cancer cell repair mechanisms. These targeted therapies aim to improve outcomes for patients with specific genetic profiles, making them a promising alternative to the standard treatment options.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial studies various treatment combinations for their potential to aid patients with non-small cell lung cancer (NSCLC) who have not responded to previous therapies. Participants in different trial arms will receive specific combinations of investigational treatments.

One arm tests the combination of durvalumab with olaparib, which has shown promise in reducing the risk of disease progression or death in certain cancers. Another arm evaluates durvalumab with danvatirsen, as research suggests this combination may double response rates compared to durvalumab alone. The combination of durvalumab and ceralasertib is also under examination, as it may enhance effectiveness in NSCLC.

Additionally, the trial includes an arm studying trastuzumab deruxtecan with durvalumab, which has demonstrated antitumor activity in HER2-altered NSCLC. Durvalumab with vistusertib is another combination under investigation, having shown positive outcomes in advanced NSCLC. Lastly, the combination of durvalumab and oleclumab is being evaluated for its potential to improve clinical outcomes in some lung cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

John Heymach, M.D, Ph.D

Principal Investigator

The University of Texas MD Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Module 9 Cohort B.9.PRI: Durvalumab 1500 mg + Ceralasertib 240 mg Experimental Treatment 2 Interventions

Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib (AZD6738) 240 mg tablets BD for 14 days from Day 15 to Day 28 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Group II: Module 9 Cohort B.9.ACQ: Durvalumab 1500 mg + Ceralasertib 240 mg Experimental Treatment 2 Interventions

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of durvalumab 1500 mg Q4W plus oral ceralasertib (AZD6738) 240 mg tablets BD for 14 days from Day 15 to Day 28 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Group III: Module 8 Cohort A.8.ATM: Ceralasertib 240 mg Experimental Treatment 1 Intervention

Participants who are ATM-deficient or with detectable aberrations in the ATM gene will receive oral ceralasertib (AZD6738) 240 mg tablets BD from Day 1 to Day 14 of each 28-day cycle, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Group IV: Module 7 Cohort B.7.ACQ: Durvalumab 1500 mg + Cediranib 20 mg Experimental Treatment 2 Interventions

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral cediranib (AZD2171) 20 mg tablets daily for 5 days on, 2 days off (starting on Cycle 1 Day 1 of durvalumab), until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Group V: Module 6 Cohort A.6.HER2m: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg Experimental Treatment 2 Interventions

Participants whose tumours harbour selected HER2 mutations will receive IV infusion of T-DXd 5.4 mg/kg Q3W in combination with IV infusion of durvalumab 1120 mg Q3W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Group VI: Module 6 Cohort A.6.HER2e: Durvalumab 1120 mg + Trastuzumab deruxtecan 5.4mg/kg Experimental Treatment 2 Interventions

Participants whose tumours express human epidermal growth factor receptor 2 (HER2) mutations will receive IV infusion of trastuzumab deruxtecan (T-DXd) 5.4 mg/kg every 3 weeks (Q3W) in combination with IV infusion of durvalumab 1120 mg Q3W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Group VII: Module 5 Cohort B.5.PRI: Durvalumab 1500 mg + Oleclumab 3000 mg Experimental Treatment 2 Interventions

Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of oleclumab 3000 mg Q2W for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Group VIII: Module 5 Cohort B.5.ACQ: Durvalumab 1500 mg + Oleclumab 3000 mg Experimental Treatment 2 Interventions

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of oleclumab 3000 mg Q2W for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Group IX: Module 5 Cohort A.5.73H: Durvalumab 1500 mg + Oleclumab 3000 mg Experimental Treatment 2 Interventions

Participants with high expression of cluster of differentiation 73 (CD73) will receive IV infusion of oleclumab 3000 mg every 2 weeks (Q2W) for 2 cycles and then Q4W thereafter in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Group X: Module 4 Cohort A.4.RIC: Durvalumab 1500 mg + Vistusertib 125 mg Experimental Treatment 2 Interventions

Participants with detectable genetic amplifications in rapamycin-insensitive companion of mechanistic target of rapamycin complex-2 (RICTOR) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral vistusertib 125 mg tablets BD on an intermittent dosing schedule of 2 days on, 5 days off, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Group XI: Module 3 Cohort B.3.PRI: Durvalumab 1500 mg + AZD6738 240 mg Experimental Treatment 2 Interventions

Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Group XII: Module 3 Cohort B.3.ACQ: Durvalumab 1500 mg + AZD6738 240 mg Experimental Treatment 2 Interventions

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Group XIII: Module 3 Cohort A.3.ATM: Durvalumab 1500 mg + AZD6738 240 mg Experimental Treatment 2 Interventions

Participants who are ataxia telangiectasia mutated (ATM)-deficiecy will receive oral AZD6738 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral AZD6738 240 mg tablet BD in each cycle between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Group XIV: Module 2 Cohort B.2.PRI: Durvalumab 1500 mg + Danvatirsen 200 mg Experimental Treatment 2 Interventions

Participants who had anti-PD-1/PD-L1 containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (PRI) will receive IV infusion of AZD9150 (danvatirsen) 200 mg as loading dose on Days 1, 3, 5 of Cycle 0 (7-day-lead-in period). Thereafter, participants will receive AZD9150 200 mg every week (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Group XV: Module 2 Cohort B.2.ACQ: Durvalumab 1500 mg + Danvatirsen 200 mg Experimental Treatment 2 Interventions

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (ACQ) will receive IV infusion of AZD9150 (danvatirsen) 200 mg as loading dose on Days 1, 3, 5 of Cycle 0 (7-day-lead-in period). Thereafter, participants will receive AZD9150 200 mg every week (QW) on Days 1, 8, 15, and 22 of each 28-day cycle in combination with IV infusion of durvalumab 1500 mg Q4W, until objective radiological disease progression, as long as, in the investigator's opinion, they were benefiting from treatment and did not meet any other discontinuation criteria.

Group XVI: Module 11 Cohort C.11.240: AZD6738 240 mg Experimental Treatment 1 Intervention

Participants, independent of their molecular aberration status, will receive oral AZD6738 tablet 240 mg for 7 days (Days 1 to 7) in each 28-day cycle until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Group XVII: Module 10 Cohort C.10.240: Durvalumab 1500 mg + Ceralasertib 240 mg Experimental Treatment 2 Interventions

Participants, independent of their molecular aberration status, will receive oral ceralasertib (AZD6738) 240 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib 240 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Group XVIII: Module 10 Cohort C.10.160: Durvalumab 1500 mg + Ceralasertib 160 mg Experimental Treatment 2 Interventions

Participants, independent of their molecular aberration status, will receive oral ceralasertib (AZD6738) 160 mg tablet BD for 7 days in Cycle 0 (Days 1 to 7). Thereafter, participants will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral ceralasertib 160 mg tablet BD between Days 22 and 28 in each 28-day cycle, until objective radiological disease progression, however, participants may continue treatment if benefiting from treatment in the investigator opinion or did not meet any other discontinuation criteria.

Group XIX: Module 1 Cohort B.1.PRI: Durvalumab 1500 mg + Olaparib 300 mg Experimental Treatment 2 Interventions

Participants who had anti-programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) containing therapy but had progression of disease within ≤ 24 weeks from the start of treatment (primary resistance; PRI) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed.

Group XX: Module 1 Cohort B.1.ACQ: Durvalumab 1500 mg + Olaparib 300 mg Experimental Treatment 2 Interventions

Participants who had progressive disease \> 24 weeks from the start of anti PD-1/PD-L1 containing therapy while still on that treatment (acquired resistance; ACQ) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed.

Group XXI: Module 1 Cohort A.1.LKB: Durvalumab 1500 mg + Olaparib 300 mg Experimental Treatment 2 Interventions

Participants with detectable aberrations in liver kinase B1 (LKB1) will receive IV infusion of durvalumab 1500 mg Q4W in combination with oral olaparib 300 mg (2 × 150 mg) tablets BD until disease progression is confirmed.

Group XXII: Module 1 Cohort A.1.HRR: Durvalumab 1500 mg + Olaparib 300 mg Experimental Treatment 2 Interventions

Participants with detectable aberrations, mutation detected in a homologous recombination repair gene (HRRm) will receive IV infusion of durvalumab 1500 mg every 4 weeks (Q4W) in combination with oral olaparib 300 mg (2 × 150 mg) tablets twice a day (BD) until disease progression is confirmed.

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

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]

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]

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]

Citations

1. nature.com nature.com/articles/s41591-024-02808-y

Biomarker-directed targeted therapy plus durvalumab in ... These results suggest a potential sensitizing effect from the addition of ceralasertib to durvalumab in post-ICB NSCLC, and our data provide ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8104

A phase II, open-label, combination therapy of durvalumab ... A phase II, open-label, combination therapy of durvalumab and ceralasertib in relapsed and refractory small cell lung cancer (SUKSES-N4).

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37843249/

Biomarker-driven phase 2 umbrella trial: Clinical efficacy of ... Targeting DDR pathways with olaparib as a single agent or in combination with ceralasertib did not meet the predefined efficacy end point.

4. blog-ecog-acrin.org blog-ecog-acrin.org/now-enrolling-ea5231-clear-study-for-patients-with-operable-non-small-cell-lung-cancer/

CLEAR Study for Operable Non-Small Cell Lung Cancer Several studies in advanced NSCLC have shown promising activity when durvalumab is given together with ceralasertib, a targeted cancer therapy.

5. esmo.org esmo.org/oncology-news/efficacy-safety-and-translational-data-from-durvalumab-plus-ceralasertib-in-advanced-metastatic-nsclc-following-prior-failure-to-anti-pd1-pd-l1-and-platinum-doublet-therapy

Efficacy, Safety, and Translational Data from Durvalumab ... A phase II umbrella HUDSON study has demonstrated an efficacy signal with durvalumab plus ceralasertib in patients with advanced/metastatic non-small cell lung ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00539331

Phase I/II Study of AZD2171 in Combination With Paclitaxel ... PART A : Safety and tolerability of AZD2171 in combination with pac/carbo in patients with non-small cell lung cancer, Assessed at each visit during Part A.

7. sciencedirect.com sciencedirect.com/science/article/pii/S155608641533118X

The Tyrosine Kinase Inhibitor Cediranib for Non-small Cell ... Cediranib (AZD2171; Recentin, AstraZeneca, Wilmington, Delaware) is a once-daily oral tyrosine kinase inhibitor that targets vascular endothelial growth ...

8. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D8480C00015

The Effects of AZD2171 in patients with Non-Small Cell ... This study is to examine the effects on tumors of AZD2171, in the treatment of NSCLC or HNC. The safety and tolerability of AZD2171 will also be studied.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4193613/

North Central Cancer Treatment Group Study N0528 - PMC ... cediranib as first-line therapy for advanced non-small cell lung cancer (NSCLC) ... We thus evaluated the efficacy, tolerability and safety of cediranib ...

10. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(24)00193-1/abstract

A Phase I Open-Label Study of Cediranib Plus Etoposide ... Cediranib (20 mg) plus etoposide and cisplatin is well tolerated and has promising clinical activity. Keywords. cediranib · Etoposide ...