Clinical trial NCT04234113: Study of Nanrilkefusp Alfa Alone and With Pembrolizumab in Adult Patients With Advanced/Metastatic Solid Tumors
Official title: A Multicenter Open-label Phase 1/1b Study to Evaluate the Safety and Preliminary Efficacy of SO-C101 as Monotherapy and in Combination With Pembrolizumab in Patients With Selected Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Thyroid Cancer
Renal Cell Carcinoma
Non Small Cell Lung Cancer
Small-cell Lung Cancer
Bladder Cancer
Melanoma
Merkel Cell Carcinoma
Skin Squamous Cell Carcinoma
Microsatellite Instability High
Triple Negative Breast Cancer
Mesothelioma
Thymic Cancer
Cervical Cancer
Biliary Tract Cancer
Hepatocellular Carcinoma
Ovarian Cancer
Gastric Cancer
Head and Neck Squamous Cell Carcinoma
Anal Cancer
Keywords: Thyroid Cancer
Renal Cell Carcinoma
Non Small Cell Lung Cancer
Small-cell Lung Cancer
Bladder Cancer
Melanoma
Merkel Cell Carcinoma
Skin Squamous Cell Carcinoma
Microsatellite Instability High
Triple Negative Breast Cancer
Mesothelioma
Thymic Cancer
Cervical Cancer
Biliary Tract Cancer
Hepatocellular Carcinoma
Ovarian Cancer
Gastric Cancer
Head and Neck Squamous Cell Carcinoma
Anal Cancer
Lead sponsor: Sotio Biotech Inc.
Sponsor class: INDUSTRY
Collaborators: name: SOTIO Biotech a.s.
First posted: 2020-01-21
Enrollment: 115
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A multicenter open-label phase 1/1b study to evaluate the safety and preliminary efficacy of nanrilkefusp alfa as monotherapy and in combination with pembrolizumab in patients with selected advanced/metastatic solid tumors

Detailed description: This study will assess the safety and tolerability of nanrilkefusp alfa administered as monotherapy and in combination with an anti-PD-1 antibody (pembrolizumab) in patients with selected relapsed/refractory advanced/metastatic solid tumors (renal cell carcinoma, non-small cell lung cancer, small-cell lung cancer, bladder cancer, melanoma, Merkel-cell carcinoma, skin squamous-cell carcinoma, microsatellite instability high solid tumors, triple-negative breast cancer, mesothelioma, thyroid cancer, thymic cancer, cervical cancer, biliary tract cancer, hepatocellular carcinoma, ovarian cancer, gastric cancer, head and neck squamous-cell carcinoma, and anal cancer).

Eligibility criteria: Inclusion criteria:

* Patients with selected histologically or cytologically confirmed advanced and/or metastatic solid tumors who are refractory to or intolerant of existing therapies known to provide clinical benefit for their condition.
* ECOG performance score 0-1. Patients with ECOG performance score 2 to be discussed with the sponsor's medical monitor to be agreed for inclusion.
* Estimated life expectancy of ≥3 months
* Washout periods: 4 weeks for chemotherapy, 4 weeks or 5 half-lives (whichever shorter) for biologic agents including immuno-oncology therapy and 4 weeks from major surgeries, definitive radiotherapy and 2 weeks after palliative radiotherapy
* At least one measurable lesion per iRECIST in a non-irradiated port. If in a previously irradiated port, must have demonstrated progression since best response to radiation therapy.
* Have fully recovered from previous treatment to grade ≤1 toxicity (excluding alopecia) or have stable grade 2 neuropathy
* Adequate organ system function
* Negative serum pregnancy test, if woman of child-bearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
* Accessible tumor tissue available for fresh biopsy

Exclusion criteria:

* Untreated central nervous system metastases and/or leptomeningeal carcinomatosis
* Known additional malignancy that is progressing and/or requires active treatment
* Prior exposure to drugs that are agonists of IL-2- or IL-15-like but not limited to rhIL-15 (NCI), ALT-803 (ALTOR), NKTR-214 (Nektar)
* History of and current interstitial lung disease or fibrosis and pneumonitis; patients with clinically significant or oxygen requiring chronic obstructive pulmonary disease or any chronic inflammatory disease (sarcoidosis etc.)
* Has received a live vaccine within 30 days of planned start of study therapy
* Absolute white blood cell count ≤2.0 ×10e9/L
* Absolute neutrophil count ≤1.0 ×10e9/L
* Platelet count ≤100×10e9/L
* Pregnant or breastfeeding women
* Any active autoimmune disease or a documented history of autoimmune disease, poorly controlled asthma, or history of syndrome that required systemic steroids (except the allowed doses) or immunosuppressive medications, except for patients with vitiligo or resolved childhood asthma/atopy
* Specific co-morbidities
* Parts B and B1:

  * Is hypersensitive to any of the ingredients of pembrolizumab drug product (KEYTRUDA®)
  * History of solid organ transplantation or hematopoietic stem cell transplantation

Primary outcomes:
measure: Part A: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: Through Cycle 1 (21 days)
measure: Part A1: Number of participants with DLTs
timeFrame: Through Cycle 1 (21 days)
measure: Part B: Number of participants with DLTs
timeFrame: Through Cycle 1 (21 days)
measure: Part B1: Number of participants with DLTs
timeFrame: Through Cycle 1 (21 days)
measure: Part A: Number of participants with AEs
timeFrame: Day 1 up to approximately 3 years
measure: Part A1: Number of participants with AEs
timeFrame: Day 1 up to approximately 3 years
measure: Part B: Number of participants with AEs
timeFrame: Day 1 up to approximately 3 years
measure: Part B1: Number of participants with AEs
timeFrame: Day 1 up to approximately 3 years
measure: Part D: Number of participants with AEs
timeFrame: Day 1 up to approximately 3 years
measure: Part A: Number of participants with serious AEs (SAEs)
timeFrame: Day 1 up to approximately 3 years
measure: Part A1: Number of participants with SAEs
timeFrame: Day 1 up to approximately 3 years
measure: Part B: Number of participants with SAEs
timeFrame: Day 1 up to approximately 3 years
measure: Part B1: Number of participants with SAEs
timeFrame: Day 1 up to approximately 3 years
measure: Part D: Number of participants with SAEs
timeFrame: Day 1 up to approximately 3 years
measure: Part A: Number of participants with AEs leading to premature discontinuation of nanrilkefusp alfa
timeFrame: Day 1 up to approximately 3 years
measure: Part A1: Number of participants with AEs leading to premature discontinuation of nanrilkefusp alfa
timeFrame: Day 1 up to approximately 3 years
measure: Part B: Number of participants with AEs leading to premature discontinuation of nanrilkefusp alfa
timeFrame: Day 1 up to approximately 3 years
measure: Part B1: Number of participants with AEs leading to premature discontinuation of nanrilkefusp alfa
timeFrame: Day 1 up to approximately 3 years
measure: Part D: Number of participants with AEs leading to premature discontinuation of nanrilkefusp alfa
timeFrame: Day 1 up to approximately 3 years
measure: Part A: Number of participants who died
timeFrame: Day 1 up to approximately 3 years
measure: Part A1: Number of participants who died
timeFrame: Day 1 up to approximately 3 years
measure: Part B: Number of participants who died
timeFrame: Day 1 up to approximately 3 years
measure: Part B1: Number of participants who died
timeFrame: Day 1 up to approximately 3 years
measure: Part D: Number of participants who died
timeFrame: Day 1 up to approximately 3 years
measure: Part A: Number of participants with nanrilkefusp alfa-related clinical laboratory test abnormalities (coagulation; hematology; clinical chemistry; urinalysis; thyroid and cardiac function)
timeFrame: Day 1 up to approximately 3 years
measure: Part A1: Number of participants with nanrilkefusp alfa-related clinical laboratory test abnormalities (coagulation; hematology; clinical chemistry; urinalysis; thyroid and cardiac function)
timeFrame: Day 1 up to approximately 3 years
measure: Part B: Number of participants with nanrilkefusp alfa-related clinical laboratory test abnormalities (coagulation; hematology; clinical chemistry; urinalysis; thyroid and cardiac function)
timeFrame: Day 1 up to approximately 3 years
measure: Part B1: Number of participants with nanrilkefusp alfa-related clinical laboratory test abnormalities (coagulation; hematology; clinical chemistry; urinalysis; thyroid and cardiac function)
timeFrame: Day 1 up to approximately 3 years
measure: Part D: Number of participants with nanrilkefusp alfa-related clinical laboratory test abnormalities (coagulation; hematology; clinical chemistry; urinalysis; thyroid and cardiac function)
timeFrame: Day 1 up to approximately 3 years
Secondary outcomes:
measure: Part A: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 1 hour (+/-15 minutes)
timeFrame: Cycle 1 Day 1, 1 hour (+/-15 minutes)
measure: Part A1: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 1 hour (+/-15 minutes)
timeFrame: Cycle 1 Day 1, 1 hour (+/-15 minutes)
measure: Part B: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 1 hour (+/-15 minutes)
timeFrame: Cycle 1 Day 1, 1 hour (+/-15 minutes)
measure: Part D: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 1 hour (+/-15 minutes)
timeFrame: Cycle 1 Day 1, 1 hour (+/-15 minutes)
measure: Part A: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 4 hours (+/-15 minutes)
timeFrame: Cycle 1 Day 1, 4 hours (+/-15 minutes)
measure: Part A1: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 4 hours (+/-15 minutes)
timeFrame: Cycle 1 Day 1, 4 hours (+/-15 minutes)
measure: Part B: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 4 hours (+/-15 minutes)
timeFrame: Cycle 1 Day 1, 4 hours (+/-15 minutes)
measure: Part D: Nanrilkefusp alfa concentration profile, Cycle 1 Day 1, 4 hours (+/-15 minutes)
timeFrame: Cycle 1 Day 1, 4 hours (+/-15 minutes)
measure: Part A: Overall activation levels of Ki-67+ CD8+ T cells on day 6 of cycle 1
timeFrame: Day 6 of Cycle 1
measure: Part A1: Overall activation levels of Ki-67+ CD8+ T cells on day 6 of cycle 1
timeFrame: Day 6 of Cycle 1
measure: Part B: Overall activation levels of Ki-67+ CD8+ T cells on day 6 of cycle 1
timeFrame: Day 6 of Cycle 1
measure: Part D: Overall activation levels of Ki-67+ CD8+ T cells on day 6 of cycle 1
timeFrame: Day 6 of Cycle 1
measure: Part A: Overall activation levels of Ki-67+ CD8+ CD45RO+ CD45RA- T cells on day 6 of cycle 1
timeFrame: Day 6 of Cycle 1
measure: Part A1: Overall activation levels of Ki-67+ CD8+ CD45RO+ CD45RA- T cells on day 6 of cycle 1
timeFrame: Day 6 of Cycle 1
measure: Part B: Overall activation levels of Ki-67+ CD8+ CD45RO+ CD45RA- T cells on day 6 of cycle 1
timeFrame: Day 6 of Cycle 1
measure: Part D: Overall activation levels of Ki-67+ CD8+ CD45RO+ CD45RA- T cells on day 6 of cycle 1
timeFrame: Day 6 of Cycle 1
measure: Part A: Overall activation levels of Ki-67+ CD4+ T cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part A1: Overall activation levels of Ki-67+ CD4+ T cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part B: Overall activation levels of Ki-67+ CD4+ T cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part D: Overall activation levels of Ki-67+ CD4+ T cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part A: Overall activation levels of Ki-67+ NK cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part A1: Overall activation levels of Ki-67+ NK cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part B: Overall activation levels of Ki-67+ NK cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part D: Overall activation levels of Ki-67+ NK cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part A: Overall activation levels of Ki-67+ NKT cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part A1: Overall activation levels of Ki-67+ NKT cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part B: Overall activation levels of Ki-67+ NKT cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part D: Overall activation levels of Ki-67+ NKT cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part A: Overall activation levels of Ki-67+ Treg cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part A1: Overall activation levels of Ki-67+ Treg cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part B: Overall activation levels of Ki-67+ Treg cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part D: Overall activation levels of Ki-67+ Treg cells on day 6 of cycle 1 at 12 μg/kg nanrilkefusp alfa
timeFrame: Day 6 of Cycle 1
measure: Part A: Objective response rate (ORR)
timeFrame: Day 1 up to approximately 3 years
measure: Part A1: ORR
timeFrame: Day 1 up to approximately 3 years
measure: Part B: ORR
timeFrame: Day 1 up to approximately 3 years
measure: Part D: ORR
timeFrame: Day 1 up to approximately 3 years
measure: Part A: Duration of response (DoR)
timeFrame: Day 1 up to approximately 3 years
measure: Part A1: DoR
timeFrame: Day 1 up to approximately 3 years
measure: Part B: DoR
timeFrame: Day 1 up to approximately 3 years
measure: Part D: DoR
timeFrame: Day 1 up to approximately 3 years
measure: Part A: Clinical benefit rate (CBR)
timeFrame: Day 1 up to approximately 3 years
measure: Part A1: CBR
timeFrame: Day 1 up to approximately 3 years
measure: Part B: CBR
timeFrame: Day 1 up to approximately 3 years
measure: Part D: CBR
timeFrame: Day 1 up to approximately 3 years
measure: Part A: Progression-free survival (PFS)
timeFrame: Day 1 up to approximately 3 years
measure: Part A1: PFS
timeFrame: Day 1 up to approximately 3 years
measure: Part B: PFS
timeFrame: Day 1 up to approximately 3 years
measure: Part D: PFS
timeFrame: Day 1 up to approximately 3 years
measure: Part A: Number of participants with anti-drug antibodies (ADAs) at the end of treatment
timeFrame: End of treatment with nanrilkefusp alfa
measure: Part A1: Number of participants with ADAs at the end of treatment
timeFrame: End of treatment with nanrilkefusp alfa
measure: Part B: Number of participants with ADAs at the end of treatment
timeFrame: End of treatment with nanrilkefusp alfa
measure: Part B1: Number of participants with ADAs at the end of treatment
timeFrame: End of treatment with nanrilkefusp alfa
measure: Part D: Number of participants with ADAs at the end of treatment
timeFrame: End of treatment with nanrilkefusp alfa
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Brno
country: Czechia
facility: Masarykův Onkologický Ústav Brno Klinika komplexní onkologické péče
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpitaux Universitaires de Marseille Timone
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Institut Gustave Roussy
city: Saint Herblain
country: France
facility: Institut de Cancerologie de L'Ouest
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology
city: Madrid
country: Spain
facility: University Hospital Sanchinarro
Study officials:
affiliation: Institute Gustave Roussy, Villejuif, France
name: Stephane Champiat, Dr.
role: PRINCIPAL_INVESTIGATOR
References: