A Trial to Evaluate the Safety of GEN1046 in Patients with Malignant Solid Tumors

Overview

About this study

The purpose of this trial is to evaluate the safety of GEN1046 in patients with malignant solid tumors.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria - Dose Escalation:

  • Subjects must have a histologically or cytologically confirmed nonCNS solid tumor that is metastatic or unresectable and for whom there is no available standard therapy likely to confer clinical benefit, or subjects who are not candidates for such available therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN1046 may be beneficial.

Inclusion Criteria - Expansion:

Expansion Cohort 1 (NSCLC): PD-1/L1 pre-treated

  • NSCLC subjects who have received up to 4 prior systemic treatment regimens (maintenance treatment is considered being part of one treatment line) for metastatic disease with radiographic disease progression on or after last prior treatment.
  • NSCLC subjects of any histology may be enrolled. Subjects with a histological or cytological diagnosis of non-squamous NSCLC must not have an epidermal growth factor (EGFR)-sensitizing mutation and/or anaplastic lymphoma (ALK) translocation / ROS1 rearrangement. EGFR sensitizing mutations are those mutations that are amenable to treatment with an approved tyrosine kinase inhibitor (TKI). Documentation of EGFR and ALK status should be available per local assessment. If documentation of EGFR and ALK status is unavailable, sponsor medical monitor approval is required prior to enrollment.
  • Subjects should have received platinum-based therapy (or alternative chemotherapy due to platinum ineligibility; e.g., a gemcitabine-containing regimen).
  • Subjects must have received prior treatment with a PD-1/L1 inhibitor alone or in combination and must have radiographic disease progression on treatment. Sponsor approval is required for subjects with a BOR of SD or PD on a CPI containing regimen with a treatment duration of up to 16 weeks.
  • Local results from the most recent PD-L1 test must be provided prior to enrollment. If local PD-L1 test results are unavailable, sponsor approval for enrollment is required.

Expansion Cohort 2 (NSCLC) - PD-1/L1 naive

  • NSCLC subjects who have received up to 4 prior systemic treatment regimens (maintenance treatment is considered being part of one treatment line) for metastatic disease with radiographic disease progression on or after last prior treatment.
  • NSCLC subjects of any histology may be enrolled. Subjects with a histological or cytological diagnosis of non-squamous NSCLC must not have an epidermal growth factor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) translocation/ROS1 rearrangement. EGFR sensitizing mutations are those mutations that are amendable to treatment with an approved TKI. Documentation of EGFR and ALK status should be available per local assessment. If documentation of EGFR and ALK status is unavailable, sponsor medical monitor approval is required prior to enrollment.
  • Subjects should have received platinum-based therapy (or alternative chemotherapy due to platinum ineligibility; e.g., a gemcitabine-containing regimen).
  • Subjects must not have received prior treatment with a PD-1/L1 inhibitor.

Expansion Cohort 3 (UC):

  • UC (of the bladder, ureter, urethra, or renal pelvis) subjects who have received up to 4 prior systemic treatment regimens (maintenance treatment is considered being part of one treatment line) for locally advanced/metastatic disease with radiographic disease progression on or after last prior treatment.
  • Subjects must have received prior treatment with a PD-1/L1 inhibitor alone or in combination and must have radiographic disease progression on treatment. Sponsor approval is required for subjects with a BOR of SD or PD on a CPI containing regimen with a treatment duration of up to 16 weeks.
  • Local results from the most recent PD-L1 test should be provided prior to enrollment (if available).

Cohort 3a:

For subjects who are eligible to receive platinum-based therapy:

  • Subjects must have received platinum-based chemotherapy.

Cohort 3b:

For subjects ineligible to receive platinum-based therapy:

  • Subjects must not be eligible for any platinum-based or any cisplatin-containing chemotherapy.

Expansion Cohort 4 (EC):

  • EC subjects who have received up to 4 prior systemic treatment regimens (maintenance treatment is considered being part of one treatment line) for advanced/metastatic disease with radiographic disease progression on or after last prior treatment.
  • Subjects must have epithelial endometrial histology including: endometrioid, serous, squamous, clear-cell carcinoma, or carcinosarcoma. Note: Sarcomas and mesenchymal EC are excluded.
  • Subjects must not have received prior treatment with a PD-1/L1 inhibitor (established local label / access need to be respected).
  • Local results of the most recent dMMR or MSI status as per local assessment should be provided prior to enrollment (if available).

Expansion Cohort 5 (TNBC):

  • TNBC defined as HER2-negative [HER2 is negative by FISH] assay (non-amplified ratio of HER2 to CEP17 < 2.0 single probe average HER2 gene copy number < 4 signals/cell) or alternatively HER2 protein expression by IHC result is 1+ negative or IHC 0 – negative and ER and PgR negative status (defined as < 1% of cells expressing hormonal receptors via IHC analysis) as per local assessment. Subjects who have received up to 4 prior systemic treatment regimens including but not limited to anthracycline-, taxane-, antimetabolite- or microtubule inhibitor-containing regimens (maintenance treatment is considered being part of one treatment line) for locally advanced/metastatic disease with radiographic disease progression on or after last prior treatment. Local pathological confirmation of triple-negative disease is required prior to trial entry.
  • Subjects with a prior history of a breast cancer with a different phenotype must have confirmation of TNBC from a biopsy obtained after the subject’s last prior systemic therapy.
  • Local results of the most recent dMMR or MSI status as per local assessment should be provided prior to enrollment (if available).

Expansion Cohort 5 (TNBC):

  • TNBC defined as HER2-negative [HER2 is negative by FISH] assay (non-amplified ratio of HER2 to CEP17 < 2.0 single probe average HER2 gene copy number < 4 signals/cell) or alternatively HER2 protein expression by IHC result is 1+ negative or IHC 0 – negative and ER and PgR negative status (defined as < 1% of cells expressing hormonal receptors via IHC analysis) as per local assessment. Subjects who have received up to 4 prior systemic treatment regimens including but not limited to anthracycline-, taxane-, antimetabolite- or microtubule inhibitor-containing regimens (maintenance treatment is considered being part of one treatment line) for locally advanced/metastatic disease with radiographic disease progression on or after last prior treatment. Local pathological confirmation of triple-negative disease is required prior to trial entry.
  • Subjects with a prior history of a breast cancer with a different phenotype must have confirmation of TNBC from a biopsy obtained after the subject’s last prior systemic therapy.
  • Local results of the most recent dMMR or MSI status as per local assessment should be provided prior to enrollment (if available).

Cohort 5a – Subjects who have received prior treatment with a PD1/L1 inhibitor:

  • Subjects must have received prior treatment with a PD-1/L1 inhibitor alone or in combination and must have radiographic disease progression on treatment. Sponsor approval is required for subjects with a BOR of SD or PD on a CPI containing regimen with a treatment duration of up to 16 weeks.
  • Local results from the most recent PD-L1 test should be provided prior to enrollment (if available).

Cohort 5b – Subjects who have not received prior treatment with a PD-1/L1 inhibitor:

  • Subjects must not have received prior treatment with a PD-1/L1 inhibitor (established local label / access need to be respected).

Expansion Cohort 6 (SCCHN):

  • Recurrent or metastatic SCCHN (oral cavity, pharynx, larynx) subjects who have received up to 4 prior systemic treatment regimens for recurrent/metastatic disease with radiographic PD on or after last prior treatment (maintenance treatment is considered being part of one treatment line).
  • Subjects must have disease progression on or after prior therapy with platinum-based chemotherapy (alternative combination chemotherapy is acceptable if the subject’s platinum ineligibility status is documented).

Cohort 6a – Subjects who have received prior treatment with a PD1/L1 inhibitor:

  • Subjects must have received prior treatment with a PD-1/L1 inhibitor alone or in combination and must have radiographic disease progression on treatment. Sponsor approval is required for subjects with a BOR of SD or PD on a CPI containing regimen with a treatment duration of up to 16 weeks.
  • Local results from the most recent PD-L1 test should be provided prior to enrollment (if available).

Cohort 6b – Subjects who have not received prior treatment with a PD-1/L1 inhibitor:

  • Subjects must not have received prior treatment with a PD-1/L1 inhibitor (established local label / access need to be respected).

Expansion Cohort 7 (Cervical Cancer):

  • Cervical cancer subjects who have received up to 4 prior systemic treatment regimens including chemotherapy in combination with bevacizumab (according to the applicable labeling) unless the subject is ineligible for bevacizumab according to local standards (chemotherapy administered in the adjuvant or neoadjuvant setting, or in combination with radiation therapy should not be counted as a prior line of therapy) for recurrent/metastatic disease with radiographic disease progression on or after last prior treatment.
  • Subjects must have cervical cancer of squamous cell, adenocarcinoma, or adenosquamous histology.
  • Subjects must not have received prior treatment with a PD-1/L1 inhibitor (established local label / access need to be respected). Docetaxel Combination Arm (US and Israel) (NSCLC): GEN1046 in combination with docetaxel.
  • NSCLC subjects of any histology may be enrolled. Subjects with a histological or cytological diagnosis of non-squamous NSCLC must not have an EGFR-sensitizing mutation and/or ALK translocation/ROS1 rearrangement. EGFR sensitizing mutations are those mutations that are amenable to treatment with an approved TKI. Documentation of EGFR and ALK status should be available per local assessment. If documentation of EGFR and ALK status is unavailable, sponsor medical monitor approval is required prior to enrollment.
  • Subject has progressed during/after treatment with an antiPD1/Ligand 1 (L1) monoclonal antibody (mAb) administered either as monotherapy, or in combination • Subjects have progressed during/after platinum doublet chemotherapy for metastatic disease with or without an antiPD1/Ligand 1 (L1) monoclonal antibody mAb.
  • Note: Disease progression during/after PD- antiPD1/Ligand 1 (L1)1 treatment progression is defined by meeting the following criteria:
    • Has received at least 2 doses of an approved antiPD-1/L1 mAb;
    • Has demonstrated disease progression (PD) during/after PD-1/L1 as defined by RECIST 1.1.

For Both Dose Escalation and Expansion

  • Subject must have measurable disease according to RECIST 1.1.
  • Subject must have Eastern Cooperative Oncology Group (ECOG) 0-1.
  • Additional Inclusion Criteria may apply.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Cassandra Moore, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Ashish Chintakuntlawar, M.B.B.S., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Yanyan Lou, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20490430

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