advanced NSCLC and other ROS1-positive solid tumors
Conditions
Interventions
Please refer to figure 1 in the protocol.
Sponsors
Nuvalent, Inc.
Eligibility
Age
16 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Age >=18 years a. Phase 2 Cohort 2e only: Age >=12 years and weighing > 40 kg. (Patients ages 12 to 17 will only be enrolled in countries and at sites where regulations allow.) 2. Disease criteria a. Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement, determined by testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) and using a local diagnostic test or a commercial test or by a regulatory agency approved test, such as fluorescence in situ hybridization (FISH) or next generation sequencing (NGS) or reverse transcription polymerase chain reaction (RT-PCR). The report from this test is required to be submitted for eligibility. b. Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangement as determined by testing in a CLIA or equivalently accredited diagnostic lab using a local diagnostic test or a commercial test or by a regulatory agency approved test, such as FISH or NGS or RT-PCR. The report from this test is required to be submitted for eligibility. c. Cohort 2e: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (including NSCLC not eligible for Cohorts 2a-2d) with ROS1 rearrangement as determined by testing in a CLIA or equivalently accredited diagnostic lab using a local diagnostic test or a commercial test or by a regulatory agency approved test, such as FISH or NGS or RT-PCR. The report from this test is required to be submitted for eligibility. 3. Prior anticancer treatment a. Phase 1: Patients with ROS1 fusion-positive NSCLC must have previously received at least 1 prior ROS1 TKI, while those with other ROS1-positive solid tumors must have progressed on any prior therapy (includes, but is not limited to, patients whohave progressed on prior ROS1 TKIs). Any number of prior platinum-based chemotherapies with or without immunotherapy is allowed. b. Cohort 2a: Must be nai*ve to TKI therapy and up to one prior platinum-based chemotherapy (with or without immunotherapy). c. Cohort 2b: Must have received 1 prior ROS1 TKI therapy (either crizotinib or entrectinib) and no prior platinum-based chemotherapy or immunotherapy. d. Cohort 2c: Must have received 1 prior ROS1 TKI therapy (either crizotinib or entrectinib) and 1 prior platinum-based chemotherapy (with or without immunotherapy). e. Cohort 2d: Must have received at least 2 prior ROS1 TKI therapies and up to 1 prior platinum-based chemotherapy (with or without immunotherapy). f. Cohort 2e: Must have progressed on any prior therapy (includes, but is not limited to, patients who have progressed on prior ROS1 TKIs). 4. Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.1 (Eisenhauer et al, 2009; Appendix 3). Phase 2: Must have measurable disease, defined as >=1 radiologically measurable target lesion according to RECIST 1.1. Note: Patients with CNS-only disease are eligible, provided that the disease is evaluable (Phase 1) or measurable (Phase 2) and does not meet Exclusion Criterion #11. 5. Pre-treatment tumor tissue (archived, if available, or a fresh biopsy) submitted for central analysis. It is
Exclusion criteria
Exclusion criteria: 1. Patient*s cancer has a known oncogenic driver alteration other than ROS1. For example, NSCLC with a targetable mutation in EGFR, ALK, MET, RET, or BRAF; colorectal with an oncogenic KRAS, NRAS, or BRAF mutation. Investigators should discuss enrollment with the Sponsor regarding co-mutations. 2. Known allergy/hypersensitivity to excipients of NVL-520. 3. Major surgery within 4 weeks of first dose of study drug. Minor surgical procedures (eg, port insertion) are permitted, but with sufficient time for wound healing as deemed clinically appropriate. 4. Ongoing or recent anticancer therapy within the following timeframe prior to first dose of study drug (NVL-520 may be started within limits for prior TKI or chemotherapy if considered by the Investigator to be safe and within the best interest of the patient, with prior approval from the Sponsor): a.TKI or other anticancer therapy not listed below in exclusion criteria 4b or 4c: 450 msec (repeated demonstration on more than one assessment). Patient has a history of prolonged QT syndrome or Torsades de pointes. 10. Patients with clinically significant cardiovascular disease as follows:
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1 • To determine the RP2D and, if applicable, the maximum tolerated dose (MTD) of NVL-520 in patients with advanced ROS1-positive solid tumors Phase 2 • To evaluate the ORR of NVL-520 at the RP2D in patients with advanced ROS1-positive NSCLC and other solid tumors | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase I Secondary Objectives • To evaluate the overall safety and tolerability of NVL-520 • To characterize the PK profile of NVL-520 • To evaluate preliminary antitumor activity of NVL-520 in patients with advanced ROS1 positive solid tumors Phase II Secondary Objectives • To assess additional measures of clinical efficacy in patients with ROS1-positive NSCLC and other solid tumors • To evaluate the intracranial antitumor activity of NVL-520 at the RP2D in patients with advanced ROS1-positive NSCLC and other solid tumors • To characterize the safety and tolerability of NVL-520 at the RP2D • To confirm the PK profile of NVL-520 at the RP2D | — |
Countries
Netherlands
Outcome results
None listed