A Phase Ib/II Study of Rilvegostomig and Ramucirumab in Participants with Advanced or Metastatic Non-Small Cell Lung Cancer
- Trial ID
- 2024-519786-22-01
- Protocol
- D702KC00001
- Sponsor
- AstraZeneca AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the safety and tolerability of novel anti-cancer agent combinations in patients with advanced or metastatic non-small cell lung cancer. In the safety run-in phase, the study aims to determine the recommended phase 2 dose. During the dose expansion phase, the focus remains on the safety and tolerability profiles of these combinations. 4, 9
The secondary objectives include:
- Estimation of anti-tumour activity across all study parts. 5
- Assessment of the pharmacokinetic profile of the combination agents. 6
- Evaluation of the immunogenicity of the combination agents.
Participants
This clinical trial involves 146 patients diagnosed with metastatic non-small cell lung cancer. The study population includes both male and female participants within specific age ranges. Inclusion requires histologically or cytologically documented squamous or non-squamous disease classified as Stage IV according to the American Joint Committee on Cancer Edition 8, which is not amenable to curative treatment. Eligible individuals must possess measurable disease per RECIST criteria and maintain a WHO/ECOG performance status of 0 or 1. Additional requirements include adequate organ function, adequate marrow function, and a minimum life expectancy of 12 weeks. Female participants of child-bearing potential must maintain negative pregnancy tests and utilize highly effective contraception. The primary objectives are:
- Part A: Safety run-in to assess safety, tolerability, and determine the recommended phase 2 dose.
- Part B: Dose expansion to assess safety, tolerability, and estimate anti-tumour activity.
Plans and Procedures
This Phase Ib/II, open-label, multicentre platform study is designed to evaluate novel therapeutic combinations in participants diagnosed with metastatic non-small cell lung cancer. The research methodology is divided into two distinct stages. Part A consists of a safety run-in to assess the safety, tolerability, and determine the recommended phase 2 dose of novel anti-cancer agent combinations. Part B involves dose expansion to further evaluate safety and estimate anti-tumour activity. Primary endpoints for the safety components include the incidence of dose-limiting toxicities, adverse events, and changes in laboratory parameters, electrocardiograms, and vital signs. Efficacy in the expansion phase is assessed via objective response rates determined by RECIST criteria. Secondary endpoints include progression-free survival, overall survival, and pharmacokinetics. The study involves a screening process to confirm histological documentation of disease and adequate organ function. Participant involvement is subject to the completion of scheduled visits and examinations as dictated by the protocol. Early termination may occur based on clinical assessment or specific study criteria.
Treatment
The experimental treatment consists of rilvegostomig, which is administered as a solution for infusion via the intravenous route.
The experimental treatment also includes ramucirumab, provided as a Cyramza 10 mg/ml concentrate for solution for infusion and administered through intravenous injection.
Efficacy
The assessment of efficacy in participants with non-small cell lung cancer is conducted through several clinical endpoints. In Part B of the study, the primary efficacy endpoint is the objective response rate, defined as the best overall response consisting of a confirmed complete response or a confirmed partial response. This assessment is determined by the investigator at the local site according to RECIST 1.1. The analysis is performed within the Response Evaluable Analysis Set, with participants analyzed according to their planned treatment and indication.
Secondary efficacy parameters include:
- duration of response
- time to response
- discontinuation rate
- progression-free survival
- overall survival
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participant must be ≥ 18 years of age at the time of signing the informed consent.
- Participants with histologically or cytologically documented squamous or non-squamous NSCLC.
- With a current Stage IV mNSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.
- WHO/ECOG performance status of 0 or 1 at screening
- Measurable disease per RECIST
- Minimum life expectancy of 12 weeks in the opinion of the investigator
- Adequate organ and marrow function
- Contraceptive use by male or female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- Female participants of child-bearing potential: (i) Must have negative pregnancy test at screening and within 3 days prior to each administration of study intervention. (ii) If sexually active with a non-sterilised male partner, must agree to use one highly effective method of birth control from enrolment throughout the study and after last dose of study intervention as specified in each sub-study. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, spermicides only, and lactational amenorrhea method are not acceptable. Female condom and male condom should not be used together. (iii) Must not breastfeed and must not donate, or retrieve for their own use, ova from screening to after the last dose of study intervention
- Capable of giving signed informed consent
- Provision of signed and dated informed consent prior to any mandatory study-specific procedures, sampling and analysis
- Participant is willing and able to comply with the study protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
Exclusion Criteria
- Participants with any of the following are excluded: (a) Sensitising EGFR mutations or ALK fusions (documented test result is mandatory for participants with non-squamous histology). For participants with squamous histology mutation/fusion, testing is mandatory only if participant is a never smoker or in the presence of a mixed histology. (b) Documented test result for any other known genomic alteration for which a targeted therapy is approved in first line per local standard of care (eg, ROS1, NTRK fusions, BRAF V600E mutation, etc).(c) Presence of small cell and neuroendocrine histology components.
- Symptomatic brain metastases. Note: participants potentially are eligible with known asymptomatic CNS lesions that do not require local treatment according to principal investigator, or asymptomatic, adequately treated with stereotactic radiation therapy, craniotomy, gamma knife therapy, or whole brain radiotherapy, with no subsequent evidence of CNS progression. Participants must not require steroids or anticonvulsants for at least 4 weeks prior to start of study . A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and enrolment. Participants must have recovered from the acute toxic effect of radiotherapy
- Palliative radiotherapy with a limited field of radiation within 2 weeks or with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention. Note: Local treatment of isolated lesions for palliative intent is acceptable. Note: Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A minimum of one week is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to non-CNS disease.
- Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study. Note: Local surgery of isolated lesions for palliative intent is acceptable.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Participants should not receive live vaccine while receiving study intervention and up to 30 days after the last dose of study intervention. COVID-19 vaccination should not be given for 72 hours prior to administration of the first dose of study intervention.
- Participation in another clinical study with a study intervention administered in the last 12 months or the combination/comparator agent (unless the safety profile is known prior to enrolment).
- Judgement by the investigator that the individual should not participate in the study.
- Concurrent enrolment into another interventional clinical trial, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
- As judged by the investigator, any severe or uncontrolled systemic diseases, including, but not limited to, uncontrolled hypertension, and active bleeding diseases, ongoing or active known infection; interstitial lung disease/pneumonitis (of any grade); unstable and/or symptomatic venous thromboembolism, serious chronic gastrointestinal conditions associated with diarrhoea active non-infectious skin disease, psychiatric illness/social situations, substance abuse, or significant conditions which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol
- Previous enrolment in the present study.
- For females only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding or planning to become pregnant.
- Has had a prior stem cell, bone marrow, allogenic tissue, or solid organ transplant.
- History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer, localised non-invasive primary disease under surveillance and curatively treated in situ disease.
- History of clinically significant arrhythmia, cardiomyopathy of any aetiology; symptomatic congestive heart failure (as defined by New York Heart Association class ≥ 3), history of myocardial infarction within the past 6 months.
- Has an active autoimmune disease that has required systemic treatment in the past 5 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
- Spinal cord compression.
- Persistent toxicities (CTCAE ≥ Grade 2 caused by previous anti-cancer therapy excluding alopecia. (a) Participants who have the following chronic, stable Grade 2 toxicities (defined as no worsening to > Grade 2 for at least 3 months prior to study intervention and managed with standard of care treatment) which the investigator deems related to previous anti-cancer therapy can be included: (i)Chemotherapy-induced neuropathy (ii)Fatigue (iii)Vitiligo (iv) Endocrine disorders that are controlled with replacement hormone therapy). (v) Irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator (eg, hearing loss)
- Treatment with any of the following agents and interventions: (a) Any other anti-cancer agents within the following time periods prior to the first dose of study intervention (see specific sub-study for prior agents that are excluded): (i)Cytotoxic treatment: 21 days. (ii)Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is shorter). (iii)Biological products including immuno-oncology agents: 28 days. (b)Any investigational agents or study interventions from a previous clinical study: 28 days or 5 half-lives (whichever is shorter). (c)Immunosuppressive medication: except (i)Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection). (ii)Systemic corticosteroids at physiological doses not to exceed 10 mg/day of prednisone or equivalent. (iii)Steroids as premedication for hypersensitivity reactions
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Yet Recruiting | 15 Apr 2026 | 10 |
 France | Not Yet Recruiting | 15 Apr 2026 | 10 |
 Germany | Not Yet Recruiting | 15 Apr 2026 | 6 |
 Italy | Not Yet Recruiting | 15 Apr 2026 | 6 |
 The Netherlands | Not Yet Recruiting | 15 Apr 2026 | — |
 Poland | Not Yet Recruiting | 15 Apr 2026 | 7 |
 Spain | Not Yet Recruiting | 15 Apr 2026 | 10 |
| Netherlands | — | — | 7 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Cyramza 10 mg/ml concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | — | — | PRD2270201 |
Cyramza 10 mg/ml concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | — | — | PRD3031529 |
Cyramza 10 mg/ml concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | — | — | PRD2391024 |
Rilvegostomig | Test | SOLUTION FOR INFUSION | INTRAVENOUS | — | — | PRD10448215 |