Cancer Research in HKUMed
4. Lung

4.0 Lung

4.1 Clinical Trial

4.1.1 Non-Small Cell Lung Cancer (NSCLC)

Early Stage/ Locally advanced: Resectable

Second-line or Subsequent treatment (Not achieved pCR after neoadjuvant pembrolizumab + chemotherapy followed by surgery

Antibody-Drug Conjugate

MK2870-019

A Phase 3 Randomized Open-Label Study of Adjuvant Pembrolizumab With or Without MK-2870 in Participants With Resectable Stage II to IIIB (N2) NSCLC not Achieving pCR After Receiving Neoadjuvant Pembrolizumab With Platinum-based Doublet Chemotherapy Followed by Surgery

Key Inclusion Criteria:

1. Newly Diagnosed Stage II-IIIB(N2) NSCLC

2. Able to undergo surgery

3. Able to receive chemotherapy + pembrolizumab

Key Exclusion Criteria:

1. Exclude EGFR mutation

Pembrolizumab + MK2870

Vs.

Pembrolizumab

Prof. Rina Hui

Centre of Cancer Medicine

cancermed@hku.hk

3910 3339

4.1.1.1 Oncogenic Driver Mutation

4.1.1.1.1.1 EGFR, MET mutation

Locally Advanced or Metastatic

Second or Third-line treatment: Phase 3

Targeted therapy (EGFR/ MET Inhibitor)

SAFFRON (Protocol ID: D5087C00001):

A phase 3, randomized, open-label study of savolitinib in combination with osimertinib versus platinum-based doublet chemotherapy in participants with EGFR mutated MET-positive, locally advanced or metastatic non-small cell lung cancer who have progressed following treatment with osimertinib.

Key Inclusion Criteria:

1. Histologically or cytologically confirmed locally advanced or metastatic NSCLC which is not amenable to curative therapy.

2. Patients with EGFR-activating mutation (exon 19 deletion, L858R and/or T790M).

3. Previously received 1 or 2 prior line(s) of EGFR TKI treatment and progressed.

4. MET overexpression and/or amplification in tumour specimen collected following progression on prior osimertinib treatment.

Key Exclusion Criteria:

1. Prior or current treatment with a third-generation EGFR-TKI other than osimertinib.

2. Prior or current treatment with savolitinib or another MET inhibitors.

Osimertinib (EGFR inhibitor) + savolitinib (MET inhibitor)

Vs.

Carbo/Cis-platin + Pemetrexed (Chemo)

Dr. James Chung Man Ho

Department of Medicine

jhocm@hku.hk

2255 4349

4.1.1.1.1.2 EGFR mutation

Locally Advanced or Metastatic

Third-line treatment (Previously treated, failure to TKI and platinum-based therapy)

Antibody-Drug Conjugate (TROP2)

MK2870-004

Randomized, Open-label, Phase 3 Study of MK-2870 vs Chemotherapy (Docetaxel or Pemetrexed) in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) with EGFR Mutations or Other Genomic Alterations.

Key Inclusion Criteria:

1. Participants with exon 19del or exon 21 L858R EGFR mutations must have received

both of the following treatments:

a. One or 2 prior lines of EGFR TKI, which also includes a third generation TKI for participants with a T790M mutation. For those who progressed on a first and/or second generation EGFR TKI and then received platinum-based therapy, negative T790M mutation should be documented.

b. One platinum-based therapy (treatment regimen may contain anti- PD-1/PD-L1 mAb) after progression on or after EGFR TKI.

2. Participants with other genomic alterations must have received both of the following treatments:

a. One or 2 prior lines of locally recommended TKIs for the respective genomic alteration.

b. One platinum-based therapy (treatment regimen may contain anti-PD-1/PD-L1 mAb) after progression on or after TKI).

MK2870

Vs.

Docetaxel or Pemetrexed

Prof. Rina Hui

Centre of Cancer Medicine

cancermed@hku.hk

3910 3339

4.1.1.1.1.3 EGFR mutation

Locally Advanced or Metastatic

First-line treatment: Phase 3

Antibody-Drug Conjugate (TROP2)

Tropion lung 14 (Protocol ID: D516NC00001):

A phase III, open-label, randomized study of OSimertinib with or without Datopotamab Deruxtecan (Dato-Dxd), as first-line treatment in participants with epidermal growth factor receptor (EGFR) mutation positive, locally advanced or metastatic non-small cell lung cancer (TROPION- Lung 14)

Key Inclusion Criteria:

1. Histologically or cytologically documented nonsquamous NSCLC. NSCLC of mixed histology is allowed.

2. The tumour harbors 1 of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations, which may include T790M.

Key Exclusion Criteria:

1. History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence

2. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD

Dato-Dxd + Osimbertinib

vs

Osimertinib

Prof. Rina Hui

Centre of Cancer Medicine

cancermed@hku.hk

2255 1661

4.1.1.1.2.1 ALK mutation

Locally advanced

First Line treatment: Phase 3

Target therapy (ALK inhibitor)

ALKAZAR (Protocol Number: NVL-655-04):

A Phase 3 Study of the Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor Neladalkib(NVL-655) Compared to Alectinib in First-Line Treatment of Patients With ALK-Positive Advanced Non-Small Cell Lung Cancer (ALKAZAR)

Key Inclusion Criteria:

1. No prior systemic treatment for locally advanced or metastatic NSCLC

2. Histologically or cytologically confirmed advanced NSCLC which is not amenable to curative therapy.

3. Documented ALK rearrangement in tissue or blood (circulating tumor DNA [ctDNA]) as detected by an United States Food and Drug

4. Patients with NSCLC: ≥ 1 prior 2G or 3G ALK TKI

5. ≤ 2 prior hemotherapies/immunotherapies

6. ECOG PS 0, 1 or 2

Key Exclusion Criteria:

1. concurrent oncogenic drivers (e.g., EGFR/ROS1/MET/RET/BRAF alterations)

Arm A: NVL-655 QD TKI

Vs

Arm B: SOC Alectinib TKI Q4W

Dr. James Chung Man Ho

Department of Medicine

jhocm@hku.hk

2255 4349

4.1.1.1 Oncogenic Driver Mutation

4.1.1.1.4.1 KRAS mutation

Locally Advanced

First-line treatment: Phase 3

Targeted therapy (KRAS G12C inhibitor)

Study Title

Main Inclusion/Exclusion

Investigational Product

Principal Investigator

Department

Email

Contact number

CodeBreaK 202 (Protocol ID: 20190341)

A Phase 3, Multicenter, Randomized, Open-label Study Evaluating Efficacy of Sotorasib Platinum Doublet Combination Versus Pembrolizumab Platinum Doublet Combination as a Front-Line Therapy in Subjects With Stage IV or Advanced Stage IIIB/C Nonsquamous Non–Small Cell Lung Cancers, Negative for PD-L1, and Positive for KRAS p.G12C

Key Inclusion Criteria:

1. Histologically/Cytologically confirmed Stage IV or IIIB or IIIC nonsquamous NSCLC.

2. No history of systemic anticancer therapy in metastatic/non-curable settings.

3. Tumour is negative for PD-L1 expression, and positive for KRAS p.G12C mutation.

4. No molecular alterations for which targeted therapy is approved (including but not limited to EGFR or ALK alteration) other than KRAS p.G12C.

Sotorasib + Platinum Doublet

vs.

Pembrolizumab + Platinum Doublet

Prof. Victor LEE

Department of Clinical Oncology

vhflee@hku.hk

Angela IU

2255 5124

4.1.1.1 Oncogenic Driver Mutation

4.1.1.1.4.2 KRAS mutation

Advanced or Metastatic

First-line treatment: Phase 3

Targeted therapy (KRAS G12C inhibitor)

Krystal-4 (Protocol ID: CA239-0004):

Phase 3 Trial of Adagrasib in Combination with Pembrolizumab versus Pembrolizumab in Patients with Advanced Non-Small Cell Lung Cancer with KRAS G12C Mutation*with PD-L1 all comers

Key Inclusion Criteria:

1. Histologically or cytologically confirmed confirmed diagnosis of NSCLC with KRAS G12C mutation and PD-L1 all comers

2. No prior systemic therapy for advanced or metastatic disease. Prior systemic therapy/ chemoradiation in neo/adjuvant setting allowed if completed >6 months prior to 1st study dose

3. Brain metastases are allowed if :Untreated ≤ 2.0 cm or Previously treated

Key Exclusion Criteria:

1. Known HIV, chronic liver disease or active hepatitis

Adagrasib 400mg BD in Combination with Pembrolizumab 200mg IV (Q3W)

Vs

Pembrolizumab 200mg IV Q3W

Dr. James Chung Man Ho

Department of Medicine

jhocm@hku.hk

2255 4349

4.1.1.1 Oncogenic Driver Mutation

4.1.1.1.4.4 KRAS mutation

Advanced or Metastatic

First-line treatment: Phase 3

Targeted therapy (KRAS G12C inhibitor)

Krystal-7 (Protocol ID: CA239-0007):

Phase 3 Trial of Adagrasib in Combination with Pembrolizumab versus Pembrolizumab in Patients with Advanced Non-Small Cell Lung Cancer with KRAS G12C Mutation*with PD-L1 >50%

Key Inclusion Criteria:

1. Histologically or cytologically confirmed confirmed diagnosis of NSCLC with KRAS G12C mutation and PD-L1 > 50%

2. No prior systemic therapy for advanced or metastatic disease. Prior systemic therapy/ chemoradiation in neo/adjuvant setting allowed if completed >6 months prior to 1st study dose

3. Brain metastases are allowed if :Untreated ≤ 2.0 cm or Previously treated

Key Exclusion Criteria:

Known HIV, chronic liver disease or active hepatitis

Adagrasib 400mg BD in Combination with Pembrolizumab 200mg IV (Q3W)

Vs

Pembrolizumab 200mg IV Q3W

Dr. James Chung Man Ho

Department of Medicine

jhocm@hku.hk

2255 4349

4.1.1.1 Oncogenic Driver Mutation

4.1.1.1.5.1 HER2 mutation

Advanced or Metastatic

First or Subsequent-line treatment: Phase 1

Targeted Therapy (HER2 TKI Inhibitor)

BEAMION-Lung2 (Protocol ID: 1479-0008):

A Phase III, open-label, randomized, active controlled, multi-centre trial evaluating orally administered BI 1810631 compared with standard of care as first- line treatment in patients with unresectable, locally advanced or metastatic nonsquamous non-small cell lung cancer harbouring HER2 tyrosine kinase domain mutation

.

Key Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic non-haematologic malignancy

2. Treatment naïve metastatic NSCLC patients with HER mutation

Key Exclusion Criteria:

1. Clinically active CNS metastasis.

2. Active Hepatitis B/C or HIV infection.

1. 3. Previously received any HER treatment

BI 1810631 (Anti HER-2 inhibitor)

VS

SOC Pembro + chemo IV

*cross over allowed

Dr. James Chung Man Ho

Department of Medicine

jhocm@hku.hk

2255 4349

4.1.1.1.5.2 HER2 mutation

Locally Advanced or Metastatic

First-line treatment: Phase 3

Targeted therapy ( HER2 inhibitor)

BAYER22615 (Protocol ID: SOHO-02 22615):

A phase 3 open-label, randomized, active-controlled, multicenter trial to evaluate the efficacy and safety of orally administered BAY 2927088 compared with standard of care as a first-line therapy in patients with unresectable, locally advanced, or metastatic non-small cell lung cancer (NSCLC) with HER2 activating mutations

Key Inclusion Criteria:

1. Documented histologically or cytologically confirmed locally advanced NSCLC, not suitable for definitive therapy or recurrent or metastatic NSCLC at screening (small cell or mixed histologies are excluded).

2. Treatment naïve metastatic NSCLC patients with HER2 mutation

Key exclusion criteria:

1. Any history of primary brain / meningeal tumors, presence of symptomatic CNS metastases / CNS metastases that require local treatment

BAY2927088 (HER2 Inhibitor)

VS

SOC Pembrolizumab + chemotherapy

Dr. James Chung Man Ho

Department of Medicine

jhocm@hku.hk

2255 4349

4.1.1 NSCLC

4.1.1.2 Wildtype

4.1.1.2.3.1 PD-L1 ≥1%

Locally Advanced Unresectable (Stage III)

First-line treatment: Phase 3

PACIFIC-8 (Protocol ID: D9075C00001):

A Phase III, Randomised, Double-blind, Placebo-controlled, Multicentre, International Study of Durvalumab plus

Domvanalimab (AB154) in Participants with Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer Whose Disease has not Progressed Following Definitive Platinum-based

Concurrent Chemoradiation Therapy.

Key Inclusion Criteria:

1. Histologically or cytologically documented NSCLC and have been treated with concurrent CRT for locally advanced (Stage III), unresectable disease.

2. Have not progressed following definitive, platinum-based, concurrent chemoradiation therapy.

3. Tumour PD-L1 status ≥ 1%.

Key Exclusion Criteria:

1. Documented EGFR and ALK wild-type status.

2. If known, tumours harbouring mutations in ROS1, RET, MET, BRAF, NTRK1, NTRK2, and ERBB2 are excluded.

Durvalumab + Domvanalimab

Vs.

Durvalumab + Placebo

Prof. Victor LEE

Department of Clinical Oncology

vhflee@hku.hk

Angela IU

2255 5124

4.1.1 NSCLC

4.1.1.2 Wildtype

4.1.1.2.4.1 PD-L1 all comers

Metastatic (Stage IV)

First-line treatment: Phase 3

Immunotherapy (Anti-PD-1/ Anti-TIGIT Antibody), Chemotherapy

STAR-121 (Protocol ID: GS-US-626-6216):

A randomized, open-label, phase 3 study to evaluate zimberelimab and domvanalimab in combination with chemotherapy versus pembrolizumab with chemotherapy for the first-line treatment of patients with metastatic non-small cell lung cancer with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations.

Key Inclusion Criteria:

1. Both adeno- and squamous NSCLC treatment naïve patients without known genomic alternation (including ALK and EGFR).

Key Exclusion Criteria:

1. Histologically SCLC/mixed NSCLC.

2. Clinically active CNS metastases.

3. Previously treated with PD-(L)1 immune checkpoint antibody/-ies.

Zimberelimab (Anti-PD-1 Antibody) and domvanalimab (Anti-TIGIT Antibody) + Chemotherapy (Carbo/cisplatin + Pemetrexed/Paclitaxel)

Vs.

Zimberelimab (Anti-PD-1 Antibody) + Chemo-therapy

Vs.

Pembrolizumab (Anti-PD-1 Antibody) + Chemotherapy

Dr. James Chung Man Ho

Dr. Victor LEE

Department of Medicine

Department of Clinical Oncology

jhocm@hku.hk

vhflee@hku.hk

2255 4349

Angela IU

2255 5124

4.1.1.2.4.2 PD-L1 all comers

4.0 Lung

4.2.1 Supportive Cancer Care

Early Stage (Resectable)

Study Title

Main Inclusion/Exclusion

Principal Investigator

Department

Email

Contact number

A rehabilitation Program to Boost Postoperative Functional Capacity in Surgical Lung Cancer Patients: A Randomized Controlled Trial.

Key Inclusion Criteria:

1. Suspected or confirmed stage I, II, or IIIA NSCLC diagnosis

2. Scheduled to undergo lung section ≥2 weeks from commencement of the first intervention class

3. Engagement in less than 150 minutes of moderate aerobic activity per week in the past 3 months.

4. 6MWT <500 meters at baseline

5. No evidence of recurrent or progressive disease.

6. Aged 45–80.

Key Exclusion Criteria:

1. Presence of another concurrent, actively treated malignancy

2. Presence of significant comorbidities that impede ability to engage in exercise, such as congestive heart failure, orthopaedic disorders of the lower limbs or back, neurological disease, or respiratory failure.

3. Surgery scheduled in <2 weeks.

Prof. Chia-Chin Lin

School of Nursing

cclin@hku.hk

3917 6633

4.2.2 Supportive Cancer Care

Advanced or Metastatic

Effect of Tai-Chi versus Aerobic Exercise on Emotional Symptom Cluster in Late-stage Lung Cancer Patients: A Mixed-methods Intervention Evaluation with Mediation Analysis.

Key Inclusion Criteria:

1. Diagnosed with stage IIIB or IV non-small cell lung cancer confirmed by pathology, with no other cancer diagnosis within the previous year.

2. Experience of sleep disturbance, anxiety, depression, and fatigue in the past week (rating of 1 or more on a 0–10 numeric rating scale [NRS] for each symptom).

3. Able to communicate in Cantonese, Mandarin, or English.

4. Conscious and alert. Patients who meet the inclusion criteria yet are on sleep/depression/anxiety medications with a fixed dosage regimen in the past 3 months will still be included in the study to increase the generalizability of the findings.

Key Exclusion Criteria:

1. Suffering from a condition that hinders exercise performance (e.g., active neurological disorder, recent heart attack).

2. Currently participating in any other exercise or mind-body classes; and/or.

3. Performing regular exercises, defined as at least 150 minutes of moderate-intensity exercise weekly.

Prof. Chia-Chin Lin

School of Nursing

cclin@hku.hk

3917 6633