Immunotherapy + Radiotherapy for Lung Cancer

(SPRINT 2 Trial)

Overseen By Akash Shah

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Montefiore Medical Center

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Heart failure, Hepatitis, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 20

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of two combinations of immunotherapy drugs paired with personalized radiotherapy for treating locally advanced non-small cell lung cancer (NSCLC). Participants will receive either durvalumab with monalizumab or durvalumab with oleclumab, followed by radiotherapy. Those with NSCLC and a high PD-L1 tumor proportion score, indicating potential responsiveness to immunotherapy, who have not yet undergone treatment for stage II or III cancer, might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot take any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment during the trial.

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

Previous studies have shown positive safety results for the durvalumab and monalizumab combination. Research indicates that patients generally tolerate this combination well. Common side effects, such as tiredness and nausea, were reported but were usually manageable.

For the durvalumab and oleclumab combination, studies also indicate a manageable safety profile. Side effects can occur, but they are often similar to those expected from immune-boosting treatments.

Both combinations aim to strengthen the immune response against lung cancer. Participants in earlier studies generally handled these treatments well, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they combine immunotherapy with radiotherapy, potentially enhancing the effectiveness of both. Durvalumab and Monalizumab work together by blocking proteins that help cancer cells evade immune detection, boosting the body's ability to fight the cancer. Meanwhile, the combination of Durvalumab with Oleclumab targets different pathways, potentially disrupting the tumor's blood supply and immune evasion strategies. These innovative combinations aim to increase the precision and potency of cancer treatment, offering hope for improved outcomes compared to traditional chemotherapies and radiation alone.

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

This trial will evaluate the effectiveness of combining durvalumab with either monalizumab or oleclumab for treating non-small cell lung cancer (NSCLC). Research has shown that patients who took durvalumab with oleclumab had a 64.8% chance of their cancer not growing or spreading for at least 10 months. In contrast, those who took durvalumab with monalizumab had a 72.7% chance. These findings suggest these combinations might help stop tumor growth and possibly extend the time patients live without their cancer worsening. Both treatments were generally well-tolerated, causing few severe side effects. Overall, these combinations could offer new options for people with advanced NSCLC. ^{2 3 6 7 8}

Who Is on the Research Team?

Nitin R Ohri, MD

Principal Investigator

Montefiore Medical Center

Are You a Good Fit for This Trial?

This trial is for people with advanced non-small cell lung cancer (NSCLC) who have a high PD-L1 tumor score (at least 50%). Participants will be randomly assigned to one of two immunotherapy combinations and receive tailored radiotherapy.

Inclusion Criteria

My lung cancer has not been treated and is confirmed by tests.

Life expectancy of at least 12 weeks

PD-L1 testing with specific criteria

Exclusion Criteria

Specific requirements for pregnancy, breastfeeding, and birth control

Known allergy or hypersensitivity to study drugs or excipients

I have not received a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction Immunotherapy

Participants receive two cycles of dual-agent immunotherapy with durvalumab and either monalizumab or oleclumab

8 weeks

2 visits (in-person)

Radiotherapy

Participants undergo a four-week course of risk-adapted, dose-painted radiotherapy

4 weeks

4 visits (in-person)

Consolidation Immunotherapy

Participants receive up to ten cycles of dual-agent immunotherapy with durvalumab and either monalizumab or oleclumab

40 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Monalizumab
• Radiotherapy

Trial Overview The study tests the effectiveness and safety of combining durvalumab with either monalizumab or oleclumab, followed by personalized radiotherapy. The goal is to see which combination works best for NSCLC patients.

How Is the Trial Designed?

Group I: Durvalumab + Oleclumab Arm Experimental Treatment 3 Interventions

Durvalumab 1500 mg IV on day 1 and oleclumab 3000 mg IV on day 1 and 15 of a 28-day cycle for two cycles, followed by four weeks risk adapted, dose-painted radiotherapy, followed by durvalumab 1500 mg and oleclumab 3000 mg on day 1 of 28-day cycles for up to ten cycles.

Group II: Durvalumab + Monalizumab Arm Experimental Treatment 3 Interventions

Durvalumab 1500 mg IV and monalizumab 1500 mg IV on day 1 of a 28-day cycle for two cycles, followed by four weeks of risk adapted, dose-painted, radiotherapy, followed by durvalumab 1500 mg IV and monalizumab 1500 mg IV on day 1 of 28-day cycle for up to ten cycles.

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

AstraZeneca

Industry 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

Citations

1. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2836414

Durvalumab Alone or Combined With Novel Agents for ... This randomized clinical trial reports the objective response rate, progression-free survival, overall survival, and safety profile of ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.8046

Updated results from COAST, a phase 2 study of ... Key secondary endpoints: safety, PFS, and overall survival (OS). Results: From Jan 2019 to Jul 2020, 186 of 189 randomized pts received ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39023287/

PACIFIC-9: Phase III trial of durvalumab + oleclumab or ... Studies show that durvalumab lowers the risk of cancer growing or spreading, and prolongs survival, when administered after chemotherapy and ...

4. mdanderson.org mdanderson.org/newsroom/research-newsroom/pre-surgical-combination-therapy-shows-promising-results-for-nsclc.h00-159776445.html

Pre-surgical combination therapy shows promising results ... Overall, the combinations were well tolerated and had no adverse impacts on surgery. The results highlight the potential benefits of adding ...

5. innate-pharma.com innate-pharma.com/media/all-press-releases/monalizumab-data-neocoast-2-phase-2-study-early-stage-nsclc-presented-wclc-2024

Monalizumab data from NeoCOAST-2 Phase 2 study in early ... The NeoCOAST-2 platform study is intended to assess the safety and efficacy of neoadjuvant durvalumab alone or combined with novel agents and chemotherapy.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10840023/

Phase 1/2 study of monalizumab plus durvalumab in ... Though the safety profile of monalizumab combination therapy is clinically favorable and the translational data support immune activation ...

7. iaslc.org iaslc.org/iaslc-news/press-release/neocoast-2-data-shows-combination-durvalumab-novel-agents-increases

NeoCOAST-2 Data Shows Combination of Durvalumab ... Phase 2 results from the NeoCOAST-2 study demonstrated that the combination of durvalumab with Dato-DXd yielded the highest pathological complete response ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2059702925004235

A phase II study of monalizumab and durvalumab in ... In lung cancer, the addition of M to D has shown improved progression-free survival (PFS) for unresectable stage III non-small-cell lung cancer (NSCLC) and ...