Master Protocol for the Study of Rilogrotug for the Treatment of Weight Loss and Anorexia in Patients With Cancer Cachexia and mCRC or mNSCLC

The purpose of this trial is to learn whether participants who take rilogrotug gain weight, have a better appetite, and have a better quality of life than participants who do not take rilogrotug (placebo arm). Adult participants with cachexia who have also been diagnosed with metastatic colorectal or non-small cell lung cancer will be enrolled. The primary hypothesis is that after 12 weeks, rilogrotug will cause an increase from baseline in body weight and appetite (as measured by the Functional Assessment of Anorexia/Cachexia Therapy 5-item Anorexia Symptom Scale \[FAACT-5IASS\] questionnaire) compared to placebo.

Phase 2 (A), Phase 3 (B) \& (C) Inclusion Criteria (IC): * Documented histological or cytological confirmation of either mNSCLC or mCRC * For patients with mNSCLC, receiving first line (1L) systemic anticancer standard of care (SOC) treatment with standard approved regimens: the 1L systemic anticancer SOC treatments are a platinum-based doublet chemotherapy regimen, and an anti-PD-(L)1 immunotherapy * For patients with mCRC, receiving 1L systemic anticancer SOC treatment with standard approved regimens: fluorouracil-based regimens including oxaliplatin or irinotecan with or without biologics) * Documentation of informed consent by the patient or the patient's legally acceptable representative, indicating that the patient has been informed of and comprehended all pertinent aspects of the trial * Is willing and able to comply with the protocol tests and procedures * Age ≥18 years * Cachexia as defined by Fearon criteria for body weight and body mass index (BMI) (Fearon 2011) * Life expectancy ≥4months * Eastern Cooperative Oncology Group performance status 0 to 2 Phase 2 (A), Phase 3 (B) \& (C) Exclusion Criteria (EC): * Anorexia or cachexia caused by reasons other than cancer (for example, severe chronic obstructive pulmonary disease \[COPD\] with home oxygen support) * Reversible causes of reduced food intake, as determined by the Investigator. * Dysphagia, calorie-restricted diet within 6 months prior to first dose, or poor food digestion and absorption * Currently receiving tube feedings or parenteral nutrition (either total or partial) * Have received medications and/or herbal supplements to enhance appetite and/or intended to treat unintentional weight loss * Patients with uncontrolled or significant cardiovascular disease * Clinically significant recurrent ascites, pleural effusion, pericardial effusion and or significant edema * Creatinine clearance ≤30 mL/min (measured or calculated by Cockcroft and Gault equation) * Aspartate aminotransferase or alanine aminotransferase \>5 × the upper limit of normal (ULN) OR total bilirubin \>2 × ULN * Alkaline phosphatase (ALP) \>3 x ULN (ALP \>5× ULN if there is liver involvement by the tumor and/or in case of bone metastases) OLE (D) IC: * The patient completed double-blind treatment period * The patient expressed interest in participating in the optional OLE sub-study and provided a signed informed consent form specific to the OLE. * In the opinion of the Investigator, the patient continues to derive clinical benefit from study treatment, has not experienced any intolerable treatment-related toxicity of National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 6.0 Grade ≥ 2 OLE (D) EC: * None