a study of nvl-655 in patients with advanced nsclc and other solid tumors harboring alk rearrangement or activating alk mutation (alkove-1)

Conditions: Locally Advanced Solid Tumor; Metastatic Solid Tumor

Summary: phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of nvl-655, determine the recommended phase 2 dose (rp2d), and evaluate the antitumor activity in patients with advanced alk- positive (alk+) nsclc and other solid tumors. phase 1 will evaluate the overall safety and tolerability of nvl-655 and will determine the rp2d and, if applicable, the mtd of nvl-655 in patients with advanced alk+ solid tumors. phase 2 will determine the objective response rate (orr) as assessed by blinded independent central review (bicr) of nvl-655 at the rp2d. secondary objectives will include the duration of response (dor), time to response (ttr), progression-free survival (pfs), overall survival (os), and clinical benefit rate (cbr) of nvl-655 in patients with advanced alk-positive nsclc and other solid tumors.

in phase 2, study patients will be enrolled into 6 distinct cohorts: * cohort 2a: patients with locally advanced or metastatic nsclc harboring an alk rearrangement who have received 1 prior 2nd-generation alk tki (ceritinib, alectinib, or brigatinib). up to 2 prior lines of chemotherapy and/or immunotherapy are allowed. * cohort 2b: patients with locally advanced or metastatic nsclc harboring an alk rearrangement, who have received 2-3 prior alk tkis (crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib). up to 2 prior lines of chemotherapy and/or immunotherapy are allowed. * cohort 2c: patients with locally advanced or metastatic nsclc harboring an alk rearrangement, who have received lorlatinib as the only prior alk tki therapy. up to one prior line of chemotherapy and/or immunotherapy received prior to lorlatinib is allowed. * cohort 2d: patients with locally advanced or metastatic nsclc harboring an alk rearrangement, who are naïve to alk tki therapy. up to one prior line of chemotherapy and/or immunotherapy is allowed. * cohort 2e: patients with locally advanced or metastatic nsclc harboring an alk rearrangement, not eligible for other phase 2 cohorts. * cohort 2f: patients with other solid tumors harboring an alk rearrangement or activating alk mutation, who have received ≥1 prior systemic anticancer therapy, or for whom no satisfactory standard therapy exists.

Eligibility criteria:
inclusion criteria: 1. age ≥18 years, phase 2 cohort 2f only: age ≥12 years and weighing \>40 kg. 2. phase 1: histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented alk rearrangement or activating alk mutation. 3. phase 2 1. phase 2 cohorts except 2f: histologically or cytologically confirmed locally advanced or metastatic nsclc with a documented alk rearrangement 2. phase 2 cohort 2f: histologically or cytologically confirmed locally advanced or metastatic solid tumor with a documented alk rearrangement or activating alk mutation detected by certified assay. 4. phase 1: must have evaluable disease (target or nontarget) according to recist 1.1 phase 2: must have measurable disease according to recist 1.1 5. adequate organ function and bone marrow reserve exclusion criteria: 1. patient's cancer has a known oncogenic driver alteration other than alk. 2. known allergy/hypersensitivity to excipients of nvl-655. 3. major surgery within 4 weeks of the study entry 4. ongoing or anticancer therapy 5. actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.