A Study of RO7247669 Plus Platinum-Based Chemotherapy vs Pembrolizumab Plus Platinum-Based Chemotherapy in Participants With Previously Untreated Non-Small Cell Lung Cancer

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05775289

Collaborator

(none)

180

Enrollment

Locations

Arms

60.5

Anticipated Duration (Months)

25.7

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of RO7247669 in combination with platinum-based chemotherapy compared with pembrolizumab plus platinum-based chemotherapy in participants with previously untreated, locally advanced, unresectable (Stage IIIB/IIIC) or metastatic (Stage IV) non-small-cell lung cancer (NSCLC) who are not eligible to receive curative surgery and/or definitive chemoradiotherapy.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: RO7247669 Drug: Pembrolizumab Drug: Paclitaxel Drug: Pemetrexed Drug: Carboplatin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

180 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase II, Randomized, Multicenter, Double-Blind, Controlled Study of RO7247669 Plus Platinum-Based Chemotherapy Versus Pembrolizumab Plus Platinum-Based Chemotherapy in Patients With Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Actual Study Start Date :

Mar 15, 2023

Anticipated Primary Completion Date :

Mar 30, 2026

Anticipated Study Completion Date :

Mar 30, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: RO7247669 + Platinum-Based Chemotherapy Participants with non-squamous (NSQ) NSCLC will receive induction treatment with blinded RO7247669 in combination with pemetrexed and carboplatin, all on Day 1 every 3 weeks (Q3W) for four 21-day cycles, followed by Q3W maintenance therapy with blinded RO7247669 together with pemetrexed until disease progression or treatment discontinuation. Participants with squamous (SQ) NSCLC will receive blinded RO7247669 in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21 day cycles, followed by blinded RO7247669 (on Day 1) Q3W until disease progression or treatment discontinuation.	Drug: RO7247669 Participants will receive intravenous (IV) RO7247669 for four 21-day cycles Drug: Paclitaxel Participants will receive IV paclitaxel Q3W for four 21-day cycles Drug: Pemetrexed Participants will receive IV pemetrexed Q3W until disease progression or unacceptable toxicity Drug: Carboplatin Participants will receive IV carboplatin Q3W for four 21-day cycles
Active Comparator: Arm B: Pembrolizumab + Platinum-Based Chemotherapy Participants with NSQ NSCLC will receive induction treatment with blinded pembrolizumab in combination with pemetrexed and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by a maintenance therapy with blinded pembrolizumab together with pemetrexed Q3W until disease progression or treatment discontinuation. Participants with SQ NSCLC will receive blinded pembrolizumab in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by blinded pembrolizumab (on Day 1) Q3W until disease progression or treatment discontinuation.	Drug: Pembrolizumab Participants will receive IV pembrolizumab four 21-day cycles Drug: Paclitaxel Participants will receive IV paclitaxel Q3W for four 21-day cycles Drug: Pemetrexed Participants will receive IV pemetrexed Q3W until disease progression or unacceptable toxicity Drug: Carboplatin Participants will receive IV carboplatin Q3W for four 21-day cycles

Arm

Intervention/Treatment

Experimental: Arm A: RO7247669 + Platinum-Based Chemotherapy

Participants with non-squamous (NSQ) NSCLC will receive induction treatment with blinded RO7247669 in combination with pemetrexed and carboplatin, all on Day 1 every 3 weeks (Q3W) for four 21-day cycles, followed by Q3W maintenance therapy with blinded RO7247669 together with pemetrexed until disease progression or treatment discontinuation. Participants with squamous (SQ) NSCLC will receive blinded RO7247669 in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21 day cycles, followed by blinded RO7247669 (on Day 1) Q3W until disease progression or treatment discontinuation.

Drug: RO7247669

Participants will receive intravenous (IV) RO7247669 for four 21-day cycles

Drug: Paclitaxel

Participants will receive IV paclitaxel Q3W for four 21-day cycles

Drug: Pemetrexed

Participants will receive IV pemetrexed Q3W until disease progression or unacceptable toxicity

Drug: Carboplatin

Participants will receive IV carboplatin Q3W for four 21-day cycles

Active Comparator: Arm B: Pembrolizumab + Platinum-Based Chemotherapy

Participants with NSQ NSCLC will receive induction treatment with blinded pembrolizumab in combination with pemetrexed and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by a maintenance therapy with blinded pembrolizumab together with pemetrexed Q3W until disease progression or treatment discontinuation. Participants with SQ NSCLC will receive blinded pembrolizumab in combination with paclitaxel and carboplatin, all on Day 1 Q3W for four 21-day cycles, followed by blinded pembrolizumab (on Day 1) Q3W until disease progression or treatment discontinuation.

Drug: Pembrolizumab

Participants will receive IV pembrolizumab four 21-day cycles

Drug: Paclitaxel

Participants will receive IV paclitaxel Q3W for four 21-day cycles

Drug: Pemetrexed

Participants will receive IV pemetrexed Q3W until disease progression or unacceptable toxicity

Drug: Carboplatin

Participants will receive IV carboplatin Q3W for four 21-day cycles

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) [From randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) (up to 58 months)]
Objective response rate (ORR) [Two consecutive occasions at least 4 weeks apart after a complete response (CR) or partial response (PR) (up to 58 months)]

Secondary Outcome Measures

Overall survival (OS) [From randomization to death from any cause (up to 58 months)]
Duration of response (DOR) [From the first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first) (up to 58 months)]
PFS in participants with PD-L1 expression [Up to 58 months]
OS for participants with PD-L1 expression [Up to 58 months]
Change in participant-reported outcomes as assessed by the use of the European Organisation for Research and Treatment (EORTC) item libraries [Baseline to week 12]
Percentage of participants with adverse events (AEs) [Up to 58 months]
Maximum serum concentration (Cmax) of RO7247669 [Up to 58 months]
Time of maximum concentration (Tmax) of RO7247669 [Up to 58 months]
Clearance (CL) of RO7247669 [Up to 58 months]
Volume of distribution at steady state (Vss) of RO7247669 [Up to 58 months]
Area under the concentration-time curve (AUC) of RO7247669 [Up to 58 months]
Half-life (T1/2) of RO7247669 [Up to 58 months]
Plasma concentration of Carboplatin [Up to 58 weeks]
Plasma concentration of pemetrexed [Up to 58 months]
Plasma concentration of paclitaxel [Up to 58 months]
Percentage of participants with anti-drug antibodies (ADAs) [Baseline up to 58 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Histologically or cytologically documented locally advanced, unresectable (Stage IIIB/IIIC) or metastatic (Stage IV) NSCLC who are not eligible for curative surgery and/or definitive chemoradiotherapy
No prior systemic treatment for metastatic NSCLC
Known tumor PD-L1 status
Confirmed availability of representative tumor specimens
Measurable disease
Life expectancy of at least 12 weeks
Adequate hematologic and end-organ function
Negative for HIV, hepatitis B (HBV), and hepatitis C (HCV)
Adequate cardiovascular function

Exclusion Criteria:

NSCLC known to have a mutation in the EGFR gene or an ALK fusion oncogene
Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
Untreated or clinically unstable spinal cord confession
History of leptomeningeal disease
Uncontrolled tumor-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once a month or more frequently)
Uncontrolled or symptomatic hypercalcemia
Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with exceptions defined by the protocol
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography (CT) scan
Active tuberculosis (TB) or untreated latent TB
Current treatment with anti-viral therapy for HBV or HCV
Significant cardiovascular disease within 3 months prior to randomization
Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
History of malignancy other than NSCLC within 5 years prior to randomization, with the exception of malignancies with a negligible risk of metastasis or death e.g., 5-year OS] rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer
Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that could affect patient safety
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Prior allogeneic stem cell or solid organ transplantation
Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment
Treatment with investigational therapy within 28 days prior to initiation of study treatment
Any anti-cancer therapy, including hormonal therapy, within 21 days prior to initiation of study treatment
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including, but not limited to, anti-cytotoxic T lymphocyte-associated protein 4, anti-T cell immunoreceptor with Ig and tyrosine-based inhibition motif domains, anti-PD-1 and anti-PD-L1 therapeutic antibodies, and anti-LAG3) agents
Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2) within 4 weeks or 5 drug-elimination half lives (whichever is longer) prior to initiation of study treatment
Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
History of severe allergic anaphylactic reactions to chimeric or humanized antibodies, fusion proteins, or platinum-containing compounds
Known hypersensitivity to Chinese hamster ovary cell products or to any component of the RO7247669 or pembrolizumab formulation
Known allergy or hypersensitivity or other contraindication to any component of the chemotherapy regimen the patient may receive during the study
Pregnancy or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pindara Private Hospital	Benowa	Queensland	Australia	4217
2	Lyell McEwin Hospital	Adelaide	South Australia	Australia	5112
3	Monash Health	Clayton	Victoria	Australia	3168
4	Barwon Health	Geelong	Victoria	Australia	3220
5	IRCCS AOU San Martino - IST	Genova	Liguria	Italy	16132
6	Pusan National University Hospital	Busan		Korea, Republic of	602-739
7	Memorial Ankara Hastanesi	Ankara		Turkey	06520