A Phase 1/2 Trial of SRA737 in Subjects With Advanced Cancer

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 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