A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors

Phase 1

Conditions: Advanced Solid Tumors
MedDRA version: 21.1Level: PTClassification code 10028997Term: Neoplasm malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2021-000441-41-DE

Lead Sponsor: umab Therapeutics AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 405

Inclusion Criteria

Part A is not conducted in EU/EEA and, therefore, specific inclusion criteria are not described.

Part A-2: : Patients with any previously treated solid tumor-type other than hepatocellular carcinoma or intrahepatic cholangiocarcinoma, confirmed by available pathology records and/or current biopsy, that is advanced (non-resectable or metastatic), or recurrent and progressing since last anti-tumor therapy, and for which no alternative, standard therapy exists.

Part B:
• Patients with Non-small Cell Lung Cancer (NSCLC) or other protocol-specified solid tumors with locally advanced or metastatic, non-resectable disease, which has progressed despite treatment with first-line standard-of-care treatment, or first- and second-line treatment, dependent on expansion cohort.
• Prior therapy must have been completed 2-4 weeks prior to the administration of the first dose of study drug as specified per protocol according to type of prior therapy.

Part B: (all cohorts): Patients with locally advanced or metastatic, nonresectable disease per cohort specific criteria listed in the protocol:
• Cohorts B1, B3 and B7
o Patients with locally advanced or metastatic, non-resectable NSCLC and documented PD-L1 expression on =50% of tumor cells# (Cohort B1, B3) or documented PD-L1 expression on =1%-49% of tumor cells # (Cohort B7)

o Patients must have received at least 1, and a maximum of 3, previous
lines of therapy, including at least 1 previous line containing a PD-(L)1
checkpoint inhibitor (Cohort B1, B7)
For patients enrolled to Cohorts B1 and B7 in Germany, they must have received both an anti-PD-(L)1 therapy and a platinum-based chemotherapy (i.e., at least 2 prior lines of treatment) to be eligible for study entry.

•Cohort B2
o Patients with locally advanced or metastatic, non-resectable HPV-associated (i.e. HPV+ tumor) SCC of the anus, cervix, vulva, vagina, penis or oropharynx

•Cohort B4
o Patients with recurrent, persistent or metastatic ovarian, primary peritoneal or fallopian tumor carcinoma

•Cohort B5
o Patients with head and neck squamous cell cancer

•Cohort B6:
o Patients with measureable TNBC

• Cohort B8
o Patients with metastatic, non-resectable colorectal cancer (mCRC) that is MSS or MSI low
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 270
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 135

Exclusion Criteria

•Previous immediate or delayed hypersensitivity reaction or idiosyncrasy to the excipients.
•Active or prior autoimmune disease, with the following allowed exceptions:
o Vitiligo, autoimmune thyroiditis, or psoriasis (not requiring systemic treatment within 2 years), type I diabetes on stable insulin therapy or – in the view of the Investigator – resolved childhood asthma/atopy;
o Intermittent use of bronchodilators, inhaled steroids or local steroid injections including intra-articular injections;
o Hypothyroidism stabilized on HRT; and
o Celiac disease adequately controlled by diet alone.

Part A2: Treatment with any antibody targeting PD-1, CTLA-4, 4-1BB or PD-L1 or other investigational biological drugs within 5 half-lives of that antibody prior to the administration of the first dose of study drug.

Part B:
•Cohort B1 and B7:
o Treatment with any PD-L1-directed therapy within 5 (five) half-lives of the respective drug; if the half-life of the respective PD-L1 antibody is unknown, treatment with such a PD-L1 antibody within 12 weeks prior to the first dose of study drug is exclusionary.
o Previous treatment with a PD-(L)1x4-1BB specific antibody or any other treatment targeting 4-1BB
o Treatment other than anti-PD-(L)1 or chemotherapy within 28 days prior to treatment initiation or not recovered to CTCAE V5.0 Grade 1 or better from AE due to prior anti-PD-1 administration

•Cohort B2:
o Treatment other than anti-PD-1 or a platinum-based chemotherapy regimen recommended as first-line or second-line treatment by current NCCN treatment guidelines or not recovered to CTCAE V5.0 Grade 1 or better from AE due to first- or second-line treatment.
•Cohort B3:
o Any treatment other than a local standard-of-care first-line chemotherapy regimen or not recovered to CTCAE V5.0 Grade 1 or better from AE due to first-line treatment.
o Receipt of a PD-1, PD-L1, 4-1BB or CTLA-4 antibody or any other investigational biological drugs.
o EGFR tyrosine kinase activating mutations or ALK gene rearrangements.
•Cohort B4:
o Prior therapy with anti-PD-1, anti-PD-L1, anti-4-1BB or anti-CTLA-4 antibodies or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways.
o Prior chemotherapy for any abdominal or pelvic tumor other than ovarian, fallopian tube, or primary peritoneal cancer within 3 years
•Cohort B5:
o Previous checkpoint inhibitor for their disease.
•Cohort B6:
o For subgroup 1:
-Treatment with PD-1 or PD-L1 antibody within 2 weeks or 5 half-lives of first dose of study drug, respectively.
-Has not recovered to CTCAE V5.0 Grade 1 or better from AE due to prior anti-PD-1 or anti-PD-1 antibody.
-Previous treatment with anti-CTLA-4 or anti-4-1BB antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways other than the PD-1/PD-L1 pathway
o For subgroup 2:
-Prior therapy with anti-PD-1, anti-PD-L1, anti-4-1BB or anti-CTLA-4 antibodies or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways
•Cohort B8:
o Patients who have previously been treated with trifluridine/tipiracil or
regorafenib;
o Patients who have previously been treated with T-cell bispecifics, 4-1BB agonists, or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD1
o Patients who have received treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) prior initiation of study treatment
o Patien