Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Participant has locally-advanced (unresectable) or metastatic solid tumor malignancy
which is confirmed by available pathology records or current biopsy.
- Participant has at least 1 measurable lesion per Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1. Lesions situated in a previously irradiated area are considered
measurable if progression has been demonstrated in such lesions.
- Monotherapy and Combination Escalation Cohorts:
a) Participant has progressed on standard therapies, is no longer eligible for
standard therapies or has refused standard approved therapies.
- Monotherapy Expansion Cohorts:
1. Participant has progressed on standard therapies, is no longer eligible for
standard therapies or has refused standard approved therapies.
2. Participant has histologically or cytologically confirmed diagnosis of NSCLC or
melanoma (for the respective RP2D Expansion Cohort to which the participant is to
be enrolled into), or the tumor type in which confirmed response is observed and
a Response-triggered Expansion Cohort is open (for Response-triggered Expansion
Cohorts).
3. For participants in the NSCLC monotherapy expansion cohort: participant has no
actionable driver mutation (e.g., epidermal growth factor receptor [EGFR],
anaplastic lymphomas kinase [ALK], neurotropic receptor tyrosine kinase [NTRK]).
4. For participants in the NSCLC monotherapy expansion cohort: participant has
progressed after receiving a checkpoint inhibitor (as monotherapy or in
combination with chemotherapy) as the first-line therapy in the advanced setting.
- Monotherapy Dose Optimization Cohorts:
a)Participant has progressed on standard therapies, is no longer eligible for standard
therapies or has refused standard approved therapies and has the tumor type selected
by the sponsor from the response triggered/RP2D expansion cohorts that meets the
criteria for Stage 2 (for Dose Optimization). The initiation of dose optimization will
depend upon the observed safety and efficacy.
- Combination Therapy Dose Expansion Cohorts:
a) Participant has histologically or cytologically confirmed diagnosis of NSCLC and
- Stage IV
- programmed cell death protein 1(PD-L1) expression positive (tumor proportion
score [TPS] ≥ 50% measured by 22C3 assay)
- negative for actionable molecular markers
- has not received prior systemic therapy for their locally advanced or metastatic
NSCLC
- no contraindications to PD-1 or PD-L1 inhibitors. Contraindications for treatment
of PD-1/PD-L1 inhibitors may include active or previously documented autoimmune
disease and/or current use of immunosuppressive agents which would predict lack
of benefit.
- Participant has an Eastern Cooperative Oncology Group Performance Status of 0 or 1.
- (Monotherapy cohorts and combination dose escalation cohorts only):
- Participant's last dose of prior antineoplastic therapy, including any immunotherapy,
was at least 21 days prior to the first dose of Investigational Product (IP)
administration. A participant with solid tumors that have a NTRK gene fusion without a
known acquired resistance mutation or EGFR or anaplastic lymphomas kinase (ALK)
mutation-positive NSCLC is allowed to remain on EGFR tyrosine kinase inhibitor (TKI),
ALK inhibitor therapy or NTRK inhibitor therapy until 4 days prior to the first dose
of IP.
- Participants who have received radiotherapy must have completed this therapy
(including stereotactic radiosurgery) at least 2 weeks prior to the first dose of IP.
- Participant's adverse events (excluding alopecia) from prior therapy have improved to
grade 1 or baseline at least 14 days prior to the first dose of IP. Note: Participants
with type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate
replacement therapy, or skin disorders (e.g., vitiligo, psoriasis, or alopecia) not
requiring systemic treatment are allowed.
- Participant has adequate organ function prior to start of study treatment (within 7
days prior to study drug initiation) as indicated by the following laboratory values.
If a participant has received a recent blood transfusion, the laboratory tests must be
obtained >= 2 weeks after any blood transfusion: Absolute Neutrophil Count (ANC) >=
1500/µL; Platelets >= 100,000/µL; Hemoglobin >= 9 g/dL (Criterion must be met without
packed red blood cell transfusion within the 2 weeks prior. Participants can be on
stable dose of erythropoietin (approximately ≥ 3 months); Creatinine clearance >= 60
mL/min (calculated by Cockcroft-Gault equation); Total Bilirubin either (a) <= 1.5 x
ULN or (b) Direct bilirubin <= ULN and total bilirubin < 3 x ULN (for participants
with Gilbert's syndrome); aspartate aminotransferase (AST) [serum glutamic oxaloacetic
transaminase (SGOT)] and alanine aminotransferase (ALT) [serum glutamic pyruvic
transaminase (SGPT)] <= 2.5 x ULN without liver metastases (or <= 5 x ULN if liver
metastases are present); serum potassium >= 3.4 mEq/L; serum magnesium >= 1.7 mg/dL;
serum ionized calcium >= 4.7 mg/dL. Thyroid stimulating hormone (TSH) within normal
limits. Note: if TSH is not within normal limits at baseline, participant may still be
eligible if T3 and/or FT4 are within the normal limits.
- Participant has activated partial thromboplastin time and international normalized
ratio (INR) <= 1.5 x ULN and is not receiving anticoagulation.
- Female participant is not pregnant and at least one of the following conditions apply:
- Not a woman of childbearing potential (WOCBP)
- WOCBP who agrees to follow the contraceptive guidance from the time of informed
consent through at least 45 days after final ASP1570 administration or at least
120 days after pembrolizumab administration, whichever occurs later.
- Female participant must agree not to breastfeed starting at screening and throughout
the study period and for at least 45 days after final ASP1570 administration or at
least 120 days after pembrolizumab administration, whichever occurs later.
- Female participant must not donate ova starting at first dose of IP and throughout the
study period and for at least 45 days after final ASP1570 administration or at least
120 days after pembrolizumab administration, whichever occurs later.
- Male participant with female partner(s) of childbearing potential (including
breastfeeding partner) must agree to use contraception throughout the treatment period
and for at least 45 days after final ASP1570 administration or at least 120 days after
pembrolizumab administration, whichever occurs later.
- Male participant must not donate sperm during the treatment period and for at least 45
days after final ASP1570 administration or at least 120 days after pembrolizumab
administration, whichever occurs later.
- Male participant with pregnant partner(s) must agree to remain abstinent or use a
condom for the duration of the pregnancy throughout the study period and for at least
45 days after final ASP1570 administration or at least 120 days after pembrolizumab
administration, whichever occurs later.
- Participant agrees not to participate in another interventional study while receiving
study treatment in the present study.
Exclusion Criteria:
- Participant has received investigational therapy within 21 days or 5 half-lives,
whichever is shorter, prior to the first dose of ASP1570 or 4 weeks prior to the first
dose of pembrolizumab.
- Participants may continue the following therapies until 4 days prior to the start of
study intervention administration:
1. An EGFR TKI in a participant with EGFR-activating mutations (not applicable to
NSCLC monotherapy expansion cohort),
2. ALK inhibitor in a participant with an ALK mutation (not applicable to NSCLC
monotherapy expansion cohort) or,
3. NTRK inhibitor in a participant with solid tumors that have a NTRK gene fusion
without a known acquired resistance mutation (not applicable to NSCLC monotherapy
expansion cohort).
- Participant requires or has received systemic steroid therapy or any other
immunosuppressive therapy within 14 days prior to the first dose of IP. Participants
using a physiologic replacement dose of hydrocortisone or its equivalent (defined as
up to 30 mg per day of hydrocortisone and up to 10 mg prednisone) are allowed.
- Participant has received and requires strong or moderate CYP2D6 inhibitors (e.g.,
bupropion, fluoxetine, paroxetine, duloxetine, abiraterone) during the study.
- Participant has symptomatic central nervous system (CNS) metastases or participant has
evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans).
Participants with previously treated CNS metastases are eligible, if they are
clinically stable and have no evidence of CNS progression by imaging for at least 4
weeks prior to start of study treatment and are not requiring immunosuppressive doses
of systemic steroids (> 30 mg per day of hydrocortisone or > 10 mg per day of
prednisone or equivalent) for no longer than 2 weeks.
- Participant has an active autoimmune disease. Participants with type 1 diabetes
mellitus, endocrinopathies stably maintained on appropriate replacement therapy, or
skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic
treatment are allowed.
- Participant was discontinued from prior immunomodulatory therapy due to a Grade >= 3
toxicity that was mechanistically related (e.g., immune related) to the agent.
- Participant has a known history of human immunodeficiency virus (HIV) infection.
However, participants with HIV with cluster of differentiation 4 (CD4)+ T-cell counts
≥ 350 cells/µL and no history of AIDS-defining opportunistic infections within the
past 6 months are eligible. NOTE: Screening for HIV infection should be conducted per
local requirements.
- Participant has any of the following per screening serology test:
- Hepatitis A virus (HAV) antibodies (immunoglobulin M [IgM])
- Positive hepatitis B surface antigen (HBsAg) or detectable hepatitis B DNA.
Participants with negative HBsAg, positive hepatitis B core antibody (anti-HBc)
and negative hepatitis B surface antibody (anti-HBs) are eligible if hepatitis B
DNA is undetectable
- Hepatitis C virus (HCV) antibodies unless HCV RNA is undetectable
- Participant has received a live or live attenuated vaccine against infectious diseases
within 28 days prior to the first dose of IP.
- Participant has a history of immune related pneumonitis (interstitial lung disease
[ILD]), currently has pneumonitis requiring high-dose glucocorticoids.
- Participant has received prior radiotherapy within 2 weeks of start of study treatment
or have had a history of radiation pneumonitis.
Note: Participants must have recovered from all radiation-related toxicities and not
require corticosteroids. A 1-week washout is permitted for palliative radiation (≤ 2 weeks
of radiotherapy) to non-CNS disease.
- Participant has an infection requiring systemic therapy within 14 days prior to the
first dose of IP.
- Participant has received a prior allogenic hematopoietic stem cell transplant or solid
organ transplant.
- Participant is expected to require another form of antineoplastic therapy while on
study treatment.
- Participant has had a myocardial infarction or unstable angina within 6 months prior
to the start of study treatment or currently has an uncontrolled illness including,
but not limited to symptomatic congestive heart failure, clinically significant
cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric
illness/social situations that would limit compliance with study requirements.
- Participant has inadequately controlled hypertension (defined as systolic blood
pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive
medications).
- Participant has a corrected QT interval using Fridericia's formula (QTcF) > 450 msec
(for male and female participants) during screening. ECGs will be performed in
triplicate during screening. (The average of the triplicate readings will be used in
the calculation for corrected QT interval [QTc]).
- Participant has a prior malignancy, other than the current malignancy for which the
participant is seeking treatment, active (i.e., requiring treatment or intervention)
within the previous 2 years except for locally curable malignancies that have been
apparently cured, such as basal or squamous cell skin cancer, superficial bladder
cancer or carcinoma in situ of the cervix or breast.
- Participant has had a major surgical procedure and has not completely recovered within
28 days prior to the first dose of IP.
- Participant has a history of bleeding diathesis.
- Participant requires use of any anticoagulation therapy.
- Participant has any condition which makes the participant unsuitable for study
participation.
- Participant has a known or suspected hypersensitivity to ASP1570 or pembrolizumab (for
combination therapy participants only), or any components of the formulation used.
- For the combination therapies, participant has received radiation therapy to the lung
that is > 30 Gy within 6 months of the first dose of study treatment.
- For combination therapies, HIV-infected participants with a history of Kaposi sarcoma
and/or Multicentric Castleman Disease.