Treatment of Pulmonary SUlcus, Pancoast and Chest Wall Non-small Cell Lung Cancer Employing Radiation, Immuno-oncology and Resection (SUPER)

Treatment of Pulmonary SUlcus, Pancoast and Chest Wall Non-small Cell Lung Cancer

The SUPER trial is a prospective Phase II trial. It is designed for patients with stage 2 or 3 non-small cell lung cancer (NSCLC) prior to surgery.

Patients who are enrolled in this trial will receive combination of Non-ablative oligofractionated radiation (NORT) and two cycles of Durvalumab, an immunotherapy drug before their surgery.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-small Cell Lung Cancer (NSCLC); Lung Cancer Patients
• Intervention / Treatment: Radiation: Non-ablative oligofractionated radiation (NORT); Drug: Durvalumab

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fatemeh Zaeimi, MSc; Phone Number: 4163405686; Email: fatemeh.zaeimi@uhn.ca
• Study Contact Backup: Name: Marc de Perrot, MD, MSc, FRCSC; Phone Number: 4163405549; Email: marc.deperrot@uhn.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Age > 18 years at time of study entry.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Body weight >30 kg

5. Adequate normal organ and marrow function as defined below Hemoglobin ≥9.0 g/dL Absolute neutrophil count (ANC) ≥1.0 × 10^9/L Platelet count ≥75 × 10^9/L Serum bilirubin in normal range with the exception of Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal

   Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:

   Males:

   Creatinine CL (mL/min)=Weight (kg) x (140 - Age) / 72 x serum creatinine (mg/dL)

   Females:

   Creatinine CL (mL/min)=Weight (kg) x (140 - Age) x 0.85 / 72 x serum creatinine (mg/dL)

6. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
7. Must have a life expectancy of at least 12 weeks
8. Tumor amenable to biopsy
9. Patients with NSCLC stage IIB to IIIB.
10. PD-L1 positive tumors defined by tumor proportion score (TPS) >1%
11. Patient suitable for surgery and combined modality therapy in the opinion of the investigator.
12. Complete R0 resection of the primary tumor and involved lymph nodes is anticipated based on the clinical staging and radiological evaluation according to the baseline pre-treatment imaging.

Exclusion Criteria:

1. Participation in another clinical study with an investigational product during the last 8 weeks before enrollment
2. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
3. Known oncogenic driver mutations such as EGFR mutant or ALK mutant
4. The presence of N3 disease in the contralateral mediastinum, contralateral hilum, or contralateral supraclavicular lymph node confirmed histologically.

5. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Sponsor.

   Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the StudySponsor.

6. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
7. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
8. History of allogenic organ transplantation.

9. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:

   Patients with vitiligo or alopecia Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement Any chronic skin condition that does not require systemic therapy Patients without active disease in the last 5 years may be included but only after consultation with the Study Sponsor Patients with celiac disease controlled by diet alone

10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent

11. History of another primary malignancy except for:

    Malignancy treated with curative intent that does not require treatment, nor anticipated to require treatment for the duration of the study, and in the opinion of the investigator would not pose a risk of increased toxicity, or difficulty to follow the protocol and assess study endpoints Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated carcinoma in situ without evidence of disease

12. History of leptomeningeal carcinomatosis, malignant pleural effusion or distant metastasis (M1)
13. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry
14. History of active primary immunodeficiency
15. Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
16. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).

17. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:

    Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)

18. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
19. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.
20. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
21. Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.

22. Patients who have received prior anti-PD-1, anti PD-L1 or anti CTLA-4:

    Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.

    All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.

    Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE:

    Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.

    Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day.

23. Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant NORT-Durvalumab; administration of non-ablative oligofractionated radiation therapy using 12 Gy in 3 fractions in combination with two doses of durvalumab (1500 mg IV) prior to surgery.	Radiation: Non-ablative oligofractionated radiation (NORT); 12 Gy of Radiation in 3 fractions; Drug: Durvalumab; Two doses of durvalumab (1500 mg IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Measure CD8 TILs density & Major Pathological Response (MPR)	The proportion of patients achieving MPR after neoadjuvant therapy; The proportion of patients doubling the CD8 TILs density after neoadjuvant therapy.	5-6 weeks post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To explore the efficacy and safety of NORT-durvalumab	The proportion of patients achieving pCR after neoadjuvant therapy; The proportion of patients with grade 3, 4 or 5 toxicity	12 weeks post surgery

Collaborators and Investigators

• Sponsor: Marc de Perrot
• Collaborators: Ozmosis Research Inc.
• Investigators: Principal Investigator: Marc de Perrot, MD, MSc, FRCSC, UHN - Toronto General Hopsital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: 23-5501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No