A Study of TAK-500 With or Without Pembrolizumab in Adults With Select Locally Advanced or Metastatic Solid Tumors

Introduction

• Org Study ID: TAK-500-1001
• NTC ID: NCT05070247
• Lead Sponsor Name: Takeda
• Status: RECRUITING

Conditions

• Clear Cell Renal Cell Carcinoma

Brief Summary

This study is about TAK-500, given either alone or with pembrolizumab, in adults with select locally advanced or metastatic solid tumors.

The aims of the study are:

* to assess the safety profile of TAK-500 when given alone and when given with pembrolizumab.
* to assess the anti-tumor effects of TAK-500, when given alone and when given with pembrolizumab, in adults with locally advanced or metastatic solid tumors.

Participants may receive TAK-500 for up to 1 year. Participants may continue with their treatment if they have continuing benefit and if this is approved by their study doctor. Participants who are receiving TAK-500 either alone or with pembrolizumab will continue with their treatment until their disease progresses or until they or their study doctor decide they should stop this treatment.

Eligibility Criteria

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
2. Individuals with the following pathologically confirmed (cytological diagnosis is adequate) select locally advanced or metastatic solid tumors, whose disease has progressed on or are intolerant to standard therapy:

1. Gastroesophageal (esophageal, gastroesophageal junction, and gastric) adenocarcinoma, pancreatic adenocarcinoma, hepatocellular carcinoma (HCC), nonsquamous non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), mesothelioma, triple-negative breast cancer (TNBC), renal clear cell carcinoma (RCC) and nasopharyngeal carcinoma (NPC). Participants who are intolerant to all standard therapies are those who have developed clinical or laboratory abnormalities that prevent continued drug administration as evaluated by the principal investigator at the time of screening.
2. For dose expansion in 2L nonsquamous NSCLC (TAK-500 plus pembrolizumab):

* Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic nonsquamous NSCLC.
* Participants may not have a known targetable driver mutation, rearrangement or amplification (eg, EGFR, ALK, MET, ROS1, BRAF, KRASG12C, etc.).
* Must have had disease progression while on or following 1 prior line of therapy:

- Disease progression while on or following at least 6 weeks of 1 prior anti-PD-(L)1 therapy in the recurrent locally advanced or metastatic setting. OR Disease progression/recurrence within 6 months of the completion of anti-PD-(L)1 therapy if administered in the adjuvant/neoadjuvant setting. Prior anti-PD-(L)1 therapy may have been given with or without an anti-CTLA4 antibody and/or chemotherapy (eg, carboplatin and pemetrexed).
* Participants are eligible regardless of PD-L1 status.
3. For dose expansion in 3L nonsquamous NSCLC (TAK-500 SA):

* Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic nonsquamous NSCLC.
* Participants may not have a known targetable driver mutation, rearrangement or amplification (eg, EGFR, ALK, MET, ROS1, BRAF, KRASG12C, etc.).
* Must have had disease progression while on or following 2 prior lines of therapy:

* Disease progression while on or following at least 6 weeks of 1 prior anti-PD-(L)1 therapy in the recurrent locally advanced or metastatic setting OR Disease progression/recurrence within 6 months of the completion of 1 prior anti-PD-(L)1 therapy if administered in the adjuvant/neoadjuvant setting. Prior anti-PD-(L)1 therapy may have been given with or without an anti-CTLA4 antibody and/or chemotherapy (eg, carboplatin and pemetrexed).
* Participants must have had disease progression while on or after 1 or 2 lines of chemotherapy in the recurrent locally advanced or metastatic setting. If the anti-PD-(L)1 therapy is given in combination with chemotherapy, participant must have progressed on an additional line of chemotherapy.
* Participants are eligible regardless of PD-L1 status.
4. For dose expansion in 2L pancreatic adenocarcinoma (TAK-500 SA and TAK-500 plus pembrolizumab):

* Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic pancreatic adenocarcinoma.
* Must have had disease progression while on or following 1 prior line of therapy:

- One prior line of fluorouracil- or gemcitabine-based chemotherapy (eg, FOLFIRINOX, FOLFOX, FOLFIRI, gemcitabine/nab-paclitaxel) in the metastatic/recurrent locally advanced setting. Prior chemotherapy in the neoadjuvant/adjuvant setting does not qualify unless the participant had progression of disease within 6 months of completion of neoadjuvant/adjuvant chemotherapy.
* Must not have had prior exposure to anti-PD-(L)1 therapy.
* Participants with MSI-H/dMMR disease are not eligible.
* Participants are eligible regardless of PD-L1 status.
5. For dose expansion in 3L RCC (TAK-500 plus pembrolizumab):

* Participants with pathologically confirmed (cytological diagnosis is adequate) locally advanced or metastatic RCC.
* Must have had disease progression while on or following 2 prior lines of therapy:

* Disease progression while on or following at least 6 weeks of 1 prior anti-PD-(L)1 therapy in the recurrent locally advanced or metastatic setting. OR Disease progression/recurrence within 6 months of the completion of anti-PD-(L)1 therapy if administered in the adjuvant/neoadjuvant setting. Prior anti-PD-(L)1 therapy may have been given with or without an anti-CTLA4 antibody and/or an anti-VEGFR TKI.
* Participants must have had prior therapy with 1 or 2 lines of VEGFR TKIs in the metastatic/recurrent locally advanced setting. If anti-PD-(L)1 therapy was given in combination with a VEGFR TKI, the participant must have had progressive disease on an additional line of therapy (eg, VEGFR TKI or VEGFR TKI-containing combination).
* Participants are eligible regardless of PD-L1 status.
3. Must have at least 1 RECIST version 1.1 measurable lesion. Lesions in previously irradiated areas (or other local therapy) should not be selected as measurable/target lesions unless there has been demonstrated radiographic progression in that lesion. RECIST v1.1 target lesions must include at least 1 lesion that was not previously irradiated.
4. Adequate bone marrow, renal, and hepatic functions, as determined by the following laboratory parameters:

1. Absolute neutrophil count (ANC) greater than or equal to (>=) 1000/ microliter (mcL), platelet count >=75,000/mcL, and hemoglobin >= 8.0 grams per deciliter (g/dL) without growth factor support for ANC or transfusion support
2. Total bilirubin