a dose escalation and expansion study of lomvastomig, a pd-1/tim-3 bispecific antibody, in participants with advanced and/or metastatic solid tumors

Conditions: Solid Tumors; Metastatic Melanoma; Non-small Cell Lung Cancer (NSCLC); Small Cell Lung Cancer (SCLC); Esophageal Squamous Cell Carcinoma (ESCC)

Summary: this is a first-in-human, open-label, multicenter, phase i multiple-ascending dose (mad) study of single agent lomvastomig (ro7121661), an anti pd-1 (programmed death-1) and tim-3 (t-cell immunoglobulin and mucin domain 3) bispecific antibody, for participants with advanced and/or metastatic solid tumors. the study consists of 2 parts: dose escalation (part a) and expansion (parts b1, b2, b3, b4, and b5). the dose escalation part will be conducted first to determine the maximum tolerated dose (mtd) and/or recommended dose for expansion (rde) based on safety, tolerability, pharmacokinetic, and/or the pharmacodynamic profile of escalating doses of lomvastomig. the expansion part will enroll tumor-specific cohorts to evaluate anti-tumor activity of the mtd and/or rde of lomvastomig from part a (q2w) and to confirm safety and tolerability in participants with selected tumor types.


Eligibility criteria:
inclusion criteria: general inclusion criteria: * part a: patient must have histologically or cytologically confirmed advanced and/or metastatic solid tumor malignancies for which standard curative or palliative measures do not exist, are no longer effective, or are not acceptable to the patient * eastern cooperative oncology group performance status 0-1 * measurable disease as defined by response evaluation criteria in solid tumors (recist v1.1) * fresh biopsies may be required * negative hiv, hepatitis b, or hepatitis c test result * women of childbearing potential and male participants must agree to remain abstinent or use contraceptive methods as defined by the protocol additional specific inclusion criteria for participants with melanoma: * histologically confirmed, unresectable stage iii or stage iv melanoma * previously treated with approved anti-programmed death-ligand 1 (pd-l1)/anti-programmed death-1 (pd-1) agents with or without approved anti-cytotoxic t-lymphocyte-associated protein 4 (ctla-4) therapy and up to one additional treatment regimen additional specific inclusion criteria for participants with non-small cell lung cancer (nsclc) who previously received treatment for metastatic disease: * histologically confirmed advanced nsclc * previously treated with approved pd-l1/pd-1 inhibitors and platinum-based chemotherapy * not more than 2 prior lines of treatment for metastatic disease are allowed prior to enrolling to the study * participants must have experienced initial clinical benefit (stable disease or better) from most recent checkpoint inhibitor (cpi) therapy * tumor pd-l1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening additional specific inclusion criteria for participants with non-small cell lung cancer (nsclc) who previously did not receive treatment for metastatic disease: * histologically confirmed advanced nsclc * tumor pd-l1 expression as determined by immunohistochemistry assay of archival tumor tissue or tissue obtained at screening additional specific inclusion criteria for participants with small cell lung cancer (sclc): * histologically confirmed sclc * participants may have had prior chemotherapy, radiation therapy, or declined approved therapies for sclc additional specific inclusion criteria for participants with esophageal squamous cell carcinoma (escc): * participants whose major lesion was histologically confirmed as squamous cell carcinoma or adenosquamous cell carcinoma of the esophagus * patients who have previously received not more than 1 prior line of treatment for metastatic disease prior to enrolling to the study exclusion criteria: general exclusion criteria: * pregnancy, lactation, or breastfeeding * known hypersensitivity to any of the components of ro7121661 * active or untreated central nervous system (cns) metastases * an active second malignancy * evidence of concomitant diseases, metabolic dysfunction, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications * known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or other infection * treatment with oral or iv antibiotics within 2 weeks prior to cycle 1 day 1 * active or history of autoimmune disease or immune deficiency * prior treatment with adoptive cell therapies, such as car-t therapies * concurrent therapy with any other investigational drug \<28 days or 5 half-lives of the drug, whichever is shorter, prior to the first ro7247669 administration * regular immunosuppressive therapy * radiotherapy within the last 4 weeks before start of study drug treatment, with the exception of limited palliative radiotherapy * prior treatment with a t-cell immunoglobulin and mucin domain-3 (tim-3) inhibitor additional specific exclusion criteria for participants with nsclc who previously received treatment for metastatic disease: - patients with the following mutations, rearrangements, translocations are not eligible: epidermal growth factor receptor (egfr); anaplastic lymphoma kinase (alk); ros proto-oncogene 1 (ros1), brafv600e, and neurotrophic receptor tyrosine kinase (ntrk) additional specific exclusion criteria for participants with nsclc who did not previously receive treatment for metastatic disease: * prior therapy for metastatic disease * adjuvant anti-pd-1 or anti-pd-l1 therapy additional specific exclusion criteria for participants with small-cell lung cancer (sclc): - prior therapy with any immune cpis (such as anti-pd-l1/pd-1, ctla-4) additional specific exclusion criteria for participants with esophageal squamous cell carcinoma (escc): - prior therapy with any immunomodulatory agents