Table 2 Overview of AXAL in clinical studies (safety and efficacy)

Cervical cancer

Advanced

Maciag PC

I

(60)

AXAL alone

Dose escalation

• 1 × 10⁹ CFU

• 3.3 × 10⁹ CFU

• 1 × 10¹⁰ CFU

15

• Possible PR: 1 patient

• SD: 7 patients

• Progression of disease: 5 patients

• Pyrexia (100%)

• Vomiting (60%)

• Musculoskeletal pain (57%)

• Chills; headache and anemia (53%)

• Nausea and tachycardia (47%)

DLT = 1 × 10¹⁰ CFU

Persistent/recurrent/metastatic

GOG

(Huh WK)

II

(stage 1; NCT01266460)

(62)

AXAL alone

1 × 10⁹ CFU

67

• 12-month OS: 38.5%

• Median PFS: 3.1 mo

• Median OS: 7.7 mo

• PR: 1 patient

• SD: 9 patients

Drug-related AEs (38% of all AEs)

• Vomiting

• Chills

• Fatigue

• Fever

Persistent/recurrent/metastatic

Ghamande SA

I-II

(TiP; NCT02164461)

(63)

AXAL alone

Dose escalation

• 5 × 10⁹ CFU

• 1 × 10¹⁰ CFU

25

Pending

Treatment-related AEs (>3 patients)

• Chills

• Vomiting

• Hypotension

• Tachycardia

• Fever

• Nausea

Recurrent/refractory

Petit R

II

(CTRI/2010/091/001232)

(64)

AXAL ± cisplatin

1 × 10⁹ CFU + 40 mg/m²

110

• 12-mo OS: 36%

• 18-mo survival: 28%

• Response rate: 11% (6 CRs; 6 PRs)

• SD: 35 patients

• 79% of AEs: mild or moderate and unrelated to study drug

High-risk locally advanced

GOG

(Herzog TJ)

III

(TiP; NCT02853604) (65)

AXAL alone

1 × 10⁹ CFU

450

Pending

Pending

Head and neck cancer

Persistent/recurrent/metastatic

Cohen EW

I/II

(TiP; NCT02291055)

(66)

AXAL ± MEDI4736

Phase I: 1 × 10⁹ CFU +

3 mg/kg (3 + 3 design for MEDI4736 dose escalation)

Phase II: 1 × 10⁹ CFU + 10 mg/kg

66

Pending

Pending

Previously untreated, surgically resectable, stage II–IV patients (oropharyngeal cancer)

Miles B and Sikora A

II

(NCT02002182)

(67)

AXAL + transoral robotic surgery

1 × 10⁹ CFU

30 (present time: 8/9 vaccinated patients;

10 observational group patients)

• Increased Ag-specific IFN-γ (5/8) or TNF-α (78) responses at 3/5 time points (other 2 time points pending)

• Intratumoral expression of CD8 (4/8), PD-1 (6/8)

Pending

Oropharyngeal cancer

Jones TM

I

(NCT01598792)

(68)

AXAL alone

Dose escalation

• 3.3 × 10⁸ CFU

• 1 × 10⁹ CFU

• 3.3 × 10⁹ CFU

36

Pending

Pending

Anal cancer

Locally advanced

Safran H

I/II

(TiP; NCT01671488)

(69)

AXAL ± chemo-radiation (mitomycin, 5-fluorouracil, IMRT)

1 × 10⁹ CFU

25

Pending

Pending

Persistent/recurrent, locoregional/metastatic anorectal canal

Fakih M

II

(stage 2 TiP; NCT02399813)

(70)

AXAL alone

1 × 10⁹ CFU

Stage 1

• 31 patients

Stage 2

• 24 patients

Pending

Pending