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

Key Inclusion Criteria:

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

Expansion Only:

1. 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
2. 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
3. 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:

1. 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
2. Other malignancy within the past 2 years, except for adequately treated tumors
3. Ongoing toxic manifestations of previous treatments greater than NCI-CTCAE Grade 1
4. For Dose Escalation: new or progressing brain metastases. For Cohort Expansion: present or prior brain metastases
5. High medical risk because of nonmalignant systemic disease
6. Serologically positive for hepatitis B, hepatitis C or HIV
7. 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
8. Prior bone marrow transplant or extensive radiotherapy to greater than 25% of bone marrow within 8 weeks
9. Peanut allergy
10. QTcF\> 450 msec in adult males and \> 470 msec in adult females
11. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of SRA737
12. Inability to swallow capsules without chewing or crushing
13. Is a participant or plans to participate in another interventional clinical trial
14. Any other condition which in the Investigator's opinion would not make the subject a good candidate