A Phase 1/2 Study of NM21-1480 (Anti-PDL-1/Anti-4-1BB/Anti-HSA Tri-Specific Antibody) in Adult Patients with Advanced Solid Tumors.

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

Parts A and A-2 are not conducted in EU/EEA and, therefore, specific
inclusion criteria are not described.

Part B (all cohorts): Patients with locally advanced or metastatic,
non-resectable disease.

• Cohorts B1 and B7
o Patients with NSCLC

• Cohort B2
o Patients with 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 TNBC according to current ASCO/CAP guidelines that is
measurable according to RECIST1.1 criteria

Part B:
For Cohorts B1, B2, B6 (subgroup with required previous checkpoint inhibitor
therapy) and B7: Last dose of therapy with anti-PD-1 antibody must have been
received at least 2 weeks prior to the administration of the first dose of the
study drug. All cohorts (while not applicable to Cohort B5): Prior
chemotherapy must have been completed at least 4 weeks prior to the
administration of the first dose of study drug. Exceptions: Hormone
replacement therapy.

Exclusion Criteria

Key Exclusion Criteria:

Patient previously had known immediate or delayed hypersensitivity reaction or
idiosyncrasy to the excipients of investigational product (IP) or has
experienced >= Grade 3 irAEs with previous checkpoint inhibitor therapy.

Part B:
• Cohort B1 and B7:
o Treatment with PD-1 antibody within 2 weeks.
o Patients who, for the treatment of the current cancer, has received any other
treatment than anti PD 1 and/or chemotherapy prior to initiation of the study
drug or who has not recovered to CTCAE V5.0 Grade 1 or better from the AE due
to anti-PD-1 administered earlier; in addition, patients with any ongoing Grade
1 or higher AE of colitis, hepatitis, nephritis, or pneumonitis considered to
be related to previous anti-PD-1 therapy is exclusionary. However, sensory
neuropathy <=Grade 2, alopecia and endocrine disorder treated with hormone
replacement are acceptable.

• Cohort B2:
o Patients who, for the treatment of the current cancer, has received any
treatment other than anti PD 1 or a platinum-based chemotherapy regimen
recommended as first-line or second-line treatment by current National
Comprehensive Cancer Network (NCCN) treatment guidelines or who has not
recovered to CTCAE V5.0 Grade 1 or better from the AE due first- or second-line
treatment; in addition, patients with any ongoing Grade 1 or higher AE of
colitis, hepatitis, nephritis or pneumonitis considered to be related to
previous anti-PD-1 therapy is exclusionary. However, sensory neuropathy <=Grade
2, alopecia and endocrine disorders treated with hormone replacement are
acceptable.

• Cohort B4:
o Patients who have had prior therapy with anti-PD-1, anti-PD-L, anti-4-1-BB or
anti-CTLA-4 antibodies or any other antibody or drug specifically targeting
T-cell co-stimulation or immune check point pathways.
o Patients who have received prior chemotherapy for any abdominal or pelvic
tumor other than for treatment of ovarian, fallopian tube, or primary
peritoneal cancer within the last 3 years; patients may have received prior
adjuvant chemotherapy and radiotherapy for localized breast cancer, provided
that it was completed more than 2 years prior to consenting to this study, and
the patient remains free of recurrent or metastatic disease and hormonal
therapy has been discontinued; patients who have received prior radiotherapy to
any portion of the abdominal cavity or pelvis or thoracic cavity within the
last 3 years are excluded; prior radiation for localized cancer of the head and
neck or skin is permitted, provided that it was completed more than 3 years
prior to consenting to this study, and the patient remains free of recurrent or
metastatic disease.

• Cohort B5
o Patients who have previously received systemic drug therapy for their disease.

• Cohort B6
o For patients in the subgroup in which previous therapy with a checkpoint
inhibitor is required:
* Treatment with PD-1 antibody within 2 weeks prior to the first dose of study
drug
* Treatment with PD-L1 antibody within 5 half-lives prior to first dose of
study drug
* Patient who has not recovered to CTCAE V5.0 Grade 1 or better from the AE due
to anti-PD-1 or anti-PD-1 antibody administered earlier; in addition, patient
with any ongoing Grade 1 or higher AE of colitis, hepatitis, nephritis, or

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Part B<br /><br><br /><br>• BOR (Primary endpoint for Cohort B1-4, 6-7)<br /><br>• ORR (Primary endpoint for Cohort B5)<br /><br>• Incidence and severity of TEAEs with specific focus on incidence and severity<br /><br>of irAEs<br /><br>• Characterization of exposure-dependent PD markers of target and pathway<br /><br>engagement. Potential PD markers are included in the below list of exploratory<br /><br>markers applicable to all Parts A, A-2 and B</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Disease Control Rate (DCR)<br /><br>• DOR<br /><br>• PFS<br /><br>• OS<br /><br>• BOR, DCR, ORR, DOR, PFS as per iRECIST<br /><br>• PK parameters<br /><br>o AUCtau<br /><br>o AUC (0-infinity) (first dose only)<br /><br>o Cmax<br /><br>o Cmin<br /><br>o t<br /><br>o Tmax<br /><br>o z<br /><br>o CL<br /><br>o Vd<br /><br>• Frequency of specific anti-drug antibodies to NM21 1480</p><br>