Intervention: (R)-5-((4-((morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile
Trial phase: Phase 1 | Phase 2
SMILES: N#Cc1cnc(Nc2cc(NCC3CNCCO3)c(C(F)(F)F)cn2)cn1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 107
Group description: Due to the small numbers of patients in some tumor type subgroups and with the intention of displaying the overall safety profile of SRA737 in advanced solid tumors, the frequency of each AE was evaluated in the overall Safety Evaluable Population rather than by tumor type subgroups. The Safety Evaluable Population includes all enrolled subjects who receive at least 1 dose of SRA737.
Eligibility criteria:
Key Inclusion Criteria:

For Dose Escalation Only: any locally advanced or metastatic, histologically or cytologically proven solid tumor or NHL, relapsed after or progressing despite conventional treatment
Life expectancy of at least 12 weeks
World Health Organization (WHO) performance status of 0-1
Must meet select hematological and biochemical laboratory indices
Archival tumor tissue or accessible tumor and willingness to consent to a biopsy

Expansion Only:

Any locally advanced or metastatic malignancy of the following types for which no other conventional therapy is considered appropriate:

Metastatic Colorectal Cancer (CRC)
Platinum-resistant or intolerant High Grade Serious Ovarian Cancer (HGSOC)
Advanced Non-Small Cell Lung Cancer (NSCLC)
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Head and Neck Squamous Cell Carcinoma (HNSCC) or squamous cell carcinoma of the anus (SCCA).
Eligibility may be further restricted by the select number of prior regimens specific to each indication

Measurable disease per RECIST v1.1, or for mCRPC, evaluable disease per any of the following:

Measurable disease per RECIST v1.1
Increasing PSA
Circulating tumor cell (CTC) count of 5 or more cells per 7.5 ml of blood

Tumor tissue or ctDNA evidence that subject's tumor harbors a combination of mutations which are expected to confer sensitivity to Chk1 inhibition. Eligibility will be determined by the Sponsor's review of genetic abnormalities detected in genes in the following categories:

Oncogenic drivers such as MYC, CCNE1, etc.
Key tumor suppressor genes regulating G1 cell cycle progression/arrest such as RAD50, TP53, etc. For patients with NHSCC or SCCA, positive HPV status is also considered for eligibility.
The DDR pathway including BRCA1, BRCA2 and FANC. For patients with CRC, MMR genetic alterations and/or high microsatellite instability are also considered for eligibility.
Genetic indicators of replicative stress such as gain of function/amplification of Chk1 or ATR or other related gene.

Key Exclusion Criteria:

Received the following prior or current anticancer therapy:

Radiotherapy within the last 6 weeks
Endocrine therapy during the previous 4 weeks
Chemotherapy during the previous 4 weeks
Immunotherapy during the previous 6 weeks
Nitrosoureas or Mitomycin C during the previous 6 weeks
Other Investigational Medicinal Product during the 4 weeks before treatment
Any prior treatment with a Chk1 inhibitor or prior treatment with an ATR inhibitor within 6 months prior to receiving SRA737
Other malignancy within the past 2 years, except for adequately treated tumors
Ongoing toxic manifestations of previous treatments greater than NCI-CTCAE Grade 1
For Dose Escalation: new or progressing brain metastases. For Cohort Expansion: present or prior brain metastases
High medical risk because of nonmalignant systemic disease
Serologically positive for hepatitis B, hepatitis C or HIV
Serious cardiac condition, left ventricular ejection fraction < 45% at baseline, history of cardiac ischemia within the past 6 months, or prior history of cardiac arrhythmia requiring treatment
Prior bone marrow transplant or extensive radiotherapy to greater than 25% of bone marrow within 8 weeks
Peanut allergy
QTcF> 450 msec in adult males and > 470 msec in adult females
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of SRA737
Inability to swallow capsules without chewing or crushing
Is a participant or plans to participate in another interventional clinical trial
Any other condition which in the Investigator's opinion would not make the subject a good candidate